Methods and compositions for preparing biomolecule analytes from complex samples

Abstract

Methods and compositions for pre-treatment of samples suspected of comprising biomolecules such as nucleic acids and proteins, particularly complex samples, to maximize yield of detectable analytes extracted from the samples, and to minimize effects of compounds that interfere with biomolecule purification processes and / or that co-purify with biomolecules and inhibit downstream processes, e.g., biomolecule assay methods.

Description

[0001]PATENT Attorney Docket No: EXCT-42343.601 METHODS AND COMPOSITIONS FOR PREPARING BIOMOLECULE ANALYTES FROM COMPLEX SAMPLES STATEMENT REGARDING RELATED APPLICATIONS The present application claims priority to U.S. Provisional Application Serial No. 63 / 691,904, filed September 6, 2024, which is incorporated herein by reference in its entirety for all purposes. FIELD OF THE INVENTION The technology relates to treatment of complex samples for assaying different types of biomolecule analytes, e.g., nucleic acids and proteins, from a single specimen or sample. For example, embodiments of the technology relates to treating complex samples to maximize yield of target analytes (e.g., biomolecules such as nucleic acids) during extraction from the sample, and to minimize compounds that interfere with nucleic acid purification and / or that co-purify with target nucleic acids and inhibit downstream assay methods, such as polymerase chain reaction. The technology further relates to pre-treating complex samples (e.g., environmental samples such as soil, water, clay, compost, fresh or decayed plant, animal, or microbial samples, or mixtures; biological or medical samples, such as tissue, biofluids, feces, etc., or mixtures thereof) e.g., to render fluid fractions from such samples suitable for downstream nucleic acid extraction steps, such as affinity binding using proteins or capture oligonucleotides, or using non-sequence specific adsorption to binding beads or columns, and optionally to provide corresponding preparations or aliquots of the sample suitable for analysis of protein components, e.g., hemoglobin. BACKGROUND OF THE INVENTION It is often desirable to analyze analytes (e.g., nucleic acids, proteins) from complex samples. Complex samples are those that may include, for example, mixtures of analytes and cells from diverse sources, e.g., eukaryotic, prokaryotic, fungal, viral, and plant sources. Such complex samples comprise, for example, environmental samples such as soil, fermented foods or plant matter, sewage, and water. Biological samples from a subject, e.g., a human or animal subject, may also be complex and contain cells, cellular constituents, and nucleic acids and PATENT Attorney Docket No: EXCT-42343.601 proteins from bacteria, fungi, viruses, ingested foods, in combination with cells or nucleic acids and proteins from the host subject. For example, stool, urine, saliva, and biopsied material from a subject may contain both host nucleic acids and proteins and nucleic acids and proteins from other organisms, e.g., bacteria, fungi, viruses, and plants. In some instances, a large amount of extracted total analytes must be used, e.g., in a detection assay, in order to detect species of analytes that are present in low copy numbers or low amounts relative to the total amount of analytes. For example, the vast majority of nucleic acids in a human stool sample are from non-human sources, such that a large amount of total nucleic acid from a stool sample must typically be extracted in order to extract sufficient human nucleic acid for analysis. However, interfering compounds in such complex samples may reduce the yield of nucleic acid extractable from such samples, co-purify with the nucleic acid, and inhibit or otherwise alter results of downstream analytical methods, e.g., detection assays. In some instances, it is desirable to assay a single fluid sample for both nucleic acid and protein analytes. SUMMARY OF THE INVENTION The technology herein provides methods and compositions for pre-treatment of samples suspected of comprising analytes (e.g., nucleic acids and / or proteins), particularly complex samples, to maximize yield of analytes extracted from the samples, and to minimize effects of compounds that interfere with analyte purification processes and / or that co-purify with analytes and inhibit downstream processes (e.g., nucleic acid assay methods such as polymerase chain reaction or protein assay methods such as immunoassays). The technology described herein is advantageous in that it provides methods and compositions for pre-treating fluids from complex samples to remove or reduce compounds that may interfere with extraction of the analytes and / or that may co-purify with analytes and interfere with downstream assays (“interfering compounds”). For example, the technology comprises the following embodiments: 1. A method of removing at least one interfering compound from a fluid sample comprising or suspected of comprising nucleic acids, the method comprising: PATENT Attorney Docket No: EXCT-42343.601 a) combining at least a portion of a fluid sample with a silica adsorption matrix and a chaotropic agent in a mixture, wherein an interfering compound, if present in the fluid sample, is bound to the silica adsorption matrix; and b) removing or separating the silica adsorption matrix from the mixture to produce a pre-treated fluid sample comprising nucleic acids. 2. The method of embodiment 1, wherein the mixture further comprises at least one alcohol. 3. The method of embodiment 1, wherein the chaotropic agent comprises one or more of guanidine thiocyanate, guanidine isothiocyanate, and guanidine HCl. 4. The method of embodiment 1, wherein the chaotropic agent is present in the mixture in a concentration of about 2M, preferably ≤ 2M, preferably ≤ 1.9M, preferably ≤ 1.8M, preferably ≤ 1.7M, preferably ≤ 1.6M, preferably ≤ 1.5M, preferably ≤ 1.4M, preferably ≤ 1.3M, preferably ≤ 1.2M, preferably ≤ 1.1M. 5. The method of embodiment 1, wherein the chaotropic agent is present in the mixture in a concentration of ≥ 0.1M, preferably ≥ 0.2M, preferably ≥ 0.3M, preferably ≥ 0.4M, preferably ≥ 0.5M, preferably ≥ 0.6M, preferably ≥ 0.7M, preferably ≥ 0.8M, preferably ≥ 0.9M, preferably about 1.0M. 6. The method of embodiment 2, wherein the alcohol is selected from short-chain branched or unbranched alkanols having from 1 to 5 carbon atoms, preferably comprising methanol, ethanol, propanol, isopropanol, butanols or pentanols, or mixtures thereof. 7. The method of embodiment 2, wherein the alcohol is present in the mixture in a concentration of ≥1% (v / v), preferably ≥2% (v / v), preferably ≥3% (v / v), preferably ≥4% (v / v), preferably ≥5% (v / v) preferably ≥6% (v / v) preferably ≥7% (v / v) preferably ≥8% (v / v) preferably ≥9% (v / v) preferably ≥10% (v / v) preferably ≥11% (v / v) preferably ≥12% (v / v) preferably ≥13% (v / v) preferably ≥14% (v / v). PATENT Attorney Docket No: EXCT-42343.601 8. The method of embodiment 1, wherein the silica adsorption matrix in the mixture is at least 0.1 mg / mL, preferably ≥0.2 mg / mL, preferably ≥0.3 mg / mL, preferably ≥0.4 mg / mL, preferably ≥0.5 mg / mL, preferably ≥0.6 mg / mL, preferably ≥0.7 mg / mL, preferably ≥0.8 mg / mL, preferably ≥0.9 mg / mL, preferably ≥1.0 mg / mL, preferably ≥1.1 mg / mL, preferably ≥1.2 mg / mL, preferably ≥1.3 mg / mL, preferably ≥1.4 mg / mL, preferably ≥1.5 mg / mL, preferably ≥1.6 mg / mL, preferably ≥1.7 mg / mL, preferably ≥1.8 mg / mL, preferably ≥1.9 mg / mL, preferably ≥2.0 mg / mL, preferably ≥2.1 mg / mL, preferably ≥2.2 mg / mL, preferably ≥2.3 mg / mL, preferably ≥2.4 mg / mL, preferably ≥2.5 mg / mL, preferably ≥2.6 mg / mL, preferably ≥2.7 mg / mL, preferably ≥2.8 mg / mL, preferably ≥2.9 mg / mL, preferably ≥3.0 mg / mL, preferably ≥3.1 mg / mL, preferably ≥3.2 mg / mL, preferably ≥3.3 mg / mL, preferably ≥3.4 mg / mL, preferably ≥3.5 mg / mL, preferably ≥3.6 mg / mL, preferably ≥3.7 mg / mL, preferably ≥3.8 mg / mL, preferably ≥3.9 mg / mL, preferably ≥4.0 mg / mL, preferably ≥4.1 mg / mL, preferably ≥4.2 mg / mL, preferably ≥4.3 mg / mL, preferably ≥4.4 mg / mL, preferably ≥4.5 mg / mL, preferably ≥4.6 mg / mL, preferably ≥4.7 mg / mL, preferably ≥4.8 mg / mL, preferably ≥4.9 mg / mL, preferably ≥5.0 mg / ml, preferably ≥10 mg / ml, preferably ≥15 mg / ml, preferably ≥20 mg / ml, preferably ≥25 mg / ml, preferably ≥30 mg / mL, preferably ≥35 mg / mL, preferably ≥40 mg / mL, preferably ≥45 mg / mL, preferably ≥50 mg / mL, preferably ≥55 mg / mL, preferably ≥60 mg / mL, preferably ≥65 mg / mL, preferably ≥70 mg / mL, preferably ≥75 mg / mL, preferably ≥80 mg / mL, preferably ≥85 mg / mL, preferably ≥90 mg / mL, preferably ≥95 mg / mL, preferably ≥100 mg / mL, or any fractional concentration therebetween. 9. The method of any one of embodiments 1-8, wherein prior to step a) the fluid sample has an amount of total nucleic acid, and wherein the silica adsorption matrix removed or separated from the mixture comprises less than half the amount of total nucleic acid present in the fluid sample, preferably less than 40%, preferably less than 30%, preferably less than 20%, preferably less than 10%, preferably less than 5%, preferably less than 1% present in the fluid sample. 10. The method of embodiment 9, wherein the silica adsorption matrix removed or separated from the mixture is substantially free of nucleic acid. PATENT Attorney Docket No: EXCT-42343.601 11. The method of embodiment 1, wherein the silica adsorption matrix comprises beads or particles composed of or coated with silica. 12. The method of any one of embodiments 1-11, wherein the silica adsorption matrix comprises one or more of SiO2crystals, skeletons of diatoms built up from SiO2, amorphous silicon oxide, glass powder, silica gel, glass, zeolite, silica-coated beads, particles, paramagnetic particles, boron silicates, aluminum silicates, phosphosilicates, silica carbonyl, silica sulfonyl and silica phosphonyl surfaces. 13. The method of any one of embodiments 1-12, wherein the removing or separating comprises at least one of filtration and centrifugation. 14. The method of any one of embodiments 1-13, further comprising, prior to step a), providing a fluid sample. 15. The method of embodiment 14, wherein providing the fluid sample comprises dispersing a sample in a dispersing fluid. 16. The method of embodiment 15, wherein the dispersing fluid and the sample are combined in a ratio, wherein the ratio of dispersing fluid-to-sample is no more than 1:1 (v:v or v:w). 17. The method of embodiment 15, wherein the dispersing fluid and the sample are combined in a ratio, wherein the ratio of dispersing fluid-to-sample is between 1:1 and 1000:1 (v:v or v:w). 18. The method of embodiment 17, wherein the ratio of dispersing fluid-to-sample is 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, 200:1, 300:1, 400:1, 500:1, or 1000:1, including any fractional amount therebetween. 19. The method of any one of embodiments 1-18, wherein the fluid sample has a volume between 0.1 mL and 1000 mL. PATENT Attorney Docket No: EXCT-42343.601 20. The method of embodiment 19, wherein the volume of the fluid sample is from 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8.1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, to 1000 mL, including any fractional amount therebetween. 21. The method of any one of embodiments 1-18, wherein the fluid sample has a volume of more than 1000 mL. 22. The method of any one of embodiments 14-21, further comprising prior to step a), partitioning a dispersed sample into a solids fraction and a fluid fraction, wherein the fluid sample comprises at least a portion of the fluid fraction from the dispersed sample. 23. The method of embodiment 22, wherein the fluid in the dispersed sample is a dispersing fluid. 24. The method of embodiment 22, wherein the dispersed sample is selected from a bodily fluid, a homogenate, and a suspension. 25. The method of embodiment 22, further wherein providing the dispersed sample comprises dispersing sample material that is at least partially solid or semisolid in a dispersing fluid. 26. The method of embodiment 25, wherein the sample material comprises one or more of: human or animal tissues, bone marrow, plants, plant parts and extracts, fungi, microorganisms, fossil or mummified specimens, soil samples, sewage sludge, wastewater, stool, or foodstuffs. 27. The method of any one of embodiments 23-26, wherein the dispersing fluid comprises one or more of: PATENT Attorney Docket No: EXCT-42343.601 i) a chaotropic agent; ii) an alcohol; iii) a detergent; iv) a salt; v) a preservative; vi) a buffering agent; vii) a protein; viii) a protoporphyrin IX complex; ix) a nuclease inhibitor; x) a nuclease; xi) a chelating agent; xii) a protease; and xiii) a protease inhibitor. 28. The method of embodiment 27, wherein the dispersing fluid comprises a buffering agent, and one or more of i)-v) and vii)-xiii). 29. The method of embodiment 27 or 28, wherein the dispersing fluid comprises one or more buffering agents selected from HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (N-morpholino)propanesulfonic acid), a phosphate buffer, and TRIS (Tris(hydroxymethyl)aminomethane). 30. The method of any one of embodiments 27-29, wherein the dispersing fluid comprises three or more of i)-xiii). 31. The method of embodiment 30, wherein the dispersing fluid comprises three or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. PATENT Attorney Docket No: EXCT-42343.601 32. The method of embodiment 30, wherein the dispersing fluid comprises four or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. 33. The method of embodiment 30, wherein the dispersing fluid comprises a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. 34. The method of any one of embodiments 1-33, wherein the interfering compound comprises one or more of a polyphenol, a polysaccharide, a humic substance, an enzymatic inhibitor from soil, a humic polymer, an organic compound from compost, a decomposing plant material, a plant pigment, a plant cell wall, a chitin, a photosynthetic pigment, a humic acid, a fulvic acid, a phenolic polymer and / or phenolic oligomer, a tannin, a humic, and a phenolic compound. 35. The method of any one of embodiments 1-34, characterized by at least one of: a) the fluid sample comprising or suspected of comprising nucleic acids comprises DNA and RNA; b) the fluid sample comprising or suspected of comprising nucleic acids comprises DNA; c) the fluid sample comprising or suspected of comprising nucleic acids comprises RNA; d) the fluid sample comprising or suspected of comprising nucleic acids comprises single stranded nucleic acids; e) the fluid sample comprising or suspected of comprising nucleic acids comprises double-stranded nucleic acids; f) the fluid sample comprising or suspected of comprising nucleic acids comprises double-stranded DNA and / or double-stranded RNA; g) the fluid sample comprising or suspected of comprising nucleic acids comprises heteroduplexed DNA and RNA; h) the fluid sample comprising or suspected of comprising nucleic acids comprises cell-free nucleic acids; and PATENT Attorney Docket No: EXCT-42343.601 i) the fluid sample comprising or suspected of comprising nucleic acids comprises a protein analyte. 36. The method of any one of embodiments 1-35, further comprising extracting nucleic acids from the pre-treated fluid sample. 37. The method of embodiment 36, further comprising measuring an expression level of an RNA molecule of the extracted nucleic acids. 38. The method of embodiment 36, further comprising assaying a nucleic acid for one or more sequence variations selected from a sequence polymorphism, an insertion, a deletion, and a nucleotide mutation. 39. The method of embodiment 36, further comprising treating the nucleic acids with a methylation-specific reagent. 40. The method of embodiment 39, further comprising measuring a methylation state of a DNA molecule of the treated nucleic acids. 41. The method of any one of embodiments 1-40, further comprising treating the fluid sample or the pre-treated fluid sample with an assay inhibitor adsorbant. 42. The method of embodiment 41, wherein the assay inhibitor adsorbant comprises polyvinylpyrrolidone. 43. The method of embodiment 42, wherein the polyvinylpyrrolidone is in an insoluble form. 44. The method of embodiment 43, wherein the insoluble form comprises polyvinylpolypyrrolidone. PATENT Attorney Docket No: EXCT-42343.601 45. The method of any one of embodiments 41-44, wherein treating the fluid sample or the pre-treated fluid sample with an assay inhibitor adsorbant comprises removing the assay inhibitor adsorbant from the fluid sample or the pre-treated fluid sample. 46. The method of embodiment 45, wherein the removing comprises centrifugation and / or filtration. 47. The method of any one of embodiments 41-46, wherein the assay inhibitor adsorbant is added to and removed from the fluid sample prior to step a). 48. The method of any one of embodiments 41-46, wherein step a) further comprises adding the assay inhibitor adsorbant to the fluid sample in the mixture, and wherein step b) further comprises removing or separating the assay inhibitor adsorbant from the mixture. 49. The method of any one of embodiments 41-46, wherein the assay inhibitor adsorbant is added to and removed from the pre-treated fluid sample after step b). 50. The method of any one of embodiments 1-49, wherein the pH of a binding solution comprising the chaotropic agent and / or of the mixture is from about 2 to 10, preferably from about 7-9, more preferably from about 7-8. 51. The method of any one of embodiments 1-50, further comprising assaying at least a portion of the fluid sample for one or more proteins. 52. The method of embodiment 51, wherein the one or more proteins comprise hemoglobin. 53. The method of any one of embodiments 1-52, further comprising one or both of: a) heating at least a portion of the fluid sample prior to step a); and b) heating the mixture prior to step b). 54. A method for assaying analytes in a stool sample, the method comprising: PATENT Attorney Docket No: EXCT-42343.601 a) treating a first portion of a dispersed sample to produce a solids fraction and a first fluid fraction, and assaying the first fluid fraction for one or more proteins; and b) assaying nucleic acid extracted from a second portion of the dispersed sample for one or more nucleic acid marker analytes. 55. The method of embodiment 54, comprising before step b), treating a second portion of the dispersed sample with silica to form a treated second portion, wherein assaying nucleic acid extracted from a second portion of the dispersed sample comprises assaying nucleic acid extracted from the treated second portion. 56. The method of embodiment 55, wherein treating the second portion of the dispersed sample with silica comprises: a) combining the second portion of the dispersed sample with a silica adsorption matrix and a chaotropic agent in a mixture, wherein an interfering compound, if present in the dispersed sample, is bound to the silica adsorption matrix; and b) removing or separating the silica adsorption matrix from the mixture to produce a pre-treated fluid sample comprising nucleic acids. 57. The method of embodiment 56, further comprising treating one or more of the dispersed sample, the first portion of the dispersed sample, the first fluid fraction, the second portion of the dispersed sample and / or the pre-treated fluid sample with an assay inhibitor adsorbant. 58. The method of embodiment 57, wherein the assay inhibitor adsorbant comprises polyvinylpyrrolidone. 59. The method of embodiment 58, wherein the polyvinylpyrrolidone is in an insoluble form. 60. The method of embodiment 59, wherein the insoluble form comprises polyvinylpolypyrrolidone. PATENT Attorney Docket No: EXCT-42343.601 61. The method of any one of embodiments 57-60, wherein treating the dispersed sample, the first portion of the dispersed sample, the first fluid fraction, the second portion of the dispersed sample and / or the pre-treated fluid sample with an assay inhibitor adsorbant comprises removing the assay inhibitor adsorbant from the dispersed sample, the first portion of the dispersed sample, the first fluid fraction, the second portion of the dispersed sample and / or the pre-treated fluid sample. 62. The method of embodiment 61, wherein the removing comprises centrifugation and / or filtration. 63. A reagents kit for extraction of nucleic acids contained in samples, comprising one or more of: (a) a solution suitable for taking up a sample to form a homogenate, (b) a silica matrix for binding interfering compounds in a fluid fraction from the homogenate; and optionally (c) reagents and / or devices for extracting nucleic acid from a pre-treated fluid sample. 64. The reagents kit of embodiment 63, further comprising instructions for extracting the nucleic acids, optionally wherein the nucleic acids are DNA, RNA, or both. 65. The reagents kit of embodiment 63 or 64, wherein the solution comprises a dispersing fluid. 66. The reagents kit of embodiment 65, wherein the dispersing fluid comprises one or more of: i) a chaotropic agent; ii) an alcohol; iii) a detergent; iv) a salt; v) a preservative; vi) a buffering agent; PATENT Attorney Docket No: EXCT-42343.601 vii) a protein; viii) a protoporphyrin IX complex; ix) a nuclease inhibitor; x) a nuclease; xi) a chelating agent; xii) a protease; and / or xiii) a protease inhibitor. 67. The reagents kit of embodiment 66, wherein the dispersing fluid comprises a buffering agent, and one or more of i)-v) and vii)-xiii). 68. The reagents kit of embodiment 66 or 67, wherein the dispersing fluid comprises one or more buffering agents selected from HEPES, PIPES, MES, MOPS, a phosphate buffer, and TRIS. 69. The reagents kit of any one of embodiments 66-68, wherein the dispersing fluid comprises three or more of i)-xiii). 70. The reagents kit of embodiment 69, wherein the dispersing fluid comprises three or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. 71. The reagents kit of embodiment 69, wherein the dispersing fluid comprises four or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. 72. The reagents kit of embodiment 66, wherein the dispersing fluid comprises a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. 73. The reagents kit of any one of claims 63-72, further comprising an assay inhibitor adsorbant. PATENT Attorney Docket No: EXCT-42343.601 74. The reagents kit of embodiment 73, wherein the assay inhibitor adsorbant comprises polyvinylpyrrolidone. 75. The reagents kit of embodiment 74, wherein the polyvinylpyrrolidone is in an insoluble form. 76. The reagents kit of embodiment 75, wherein the insoluble form comprises polyvinylpolypyrrolidone. 77. A system for removing at least one interfering compound from a fluid sample comprising or suspected of comprising nucleic acids, the system comprising the reagents kit of any one of embodiments 63-76. DEFINITIONS To facilitate an understanding of the present technology, a number of terms and phrases are defined below. Additional definitions are set forth throughout the detailed description. Throughout the specification and claims, the following terms take the meanings explicitly associated herein, unless the context clearly dictates otherwise. The phrase “in one embodiment” as used herein does not necessarily refer to the same embodiment, though it may. Furthermore, the phrase “in another embodiment” as used herein does not necessarily refer to a different embodiment, although it may. Thus, as described below, various embodiments of the technology may be readily combined, without departing from the scope or spirit of the technology. In addition, as used herein, the term “or” is an inclusive “or” operator and is equivalent to the term “and / or” unless the context clearly dictates otherwise. The term “based on” is not exclusive and allows for being based on additional factors not described unless the context clearly dictates otherwise. In addition, throughout the specification, the meaning of “a,” “an,” and “the” include plural references. The meaning of “in” includes “in” and “on.” The transitional phrase “consisting essentially of” as used in claims in the present application limits the scope of a claim to the specified materials or steps “and those that do not PATENT Attorney Docket No: EXCT-42343.601 materially affect the basic and novel characteristic(s)” of the claimed invention, as discussed in In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976). For example, a composition “consisting essentially of” recited elements may contain an unrecited contaminant at a level such that, though present, the contaminant does not alter the function of the recited composition as compared to a pure composition, i.e., a composition “consisting of” the recited components. As used herein, the transitional term “comprising” is synonymous with “including,” “containing,” or “characterized by,” and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. The term “or more,” as used herein in reference to a number range (e.g., “one or more”), refers to a range of numbers higher than a preceding stated number. For example, the term “one or more” encompasses any of the following: one, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, twenty or more, fifty or more, 100 or more, or an even greater number. Conversely, the terms “or less” and “or fewer” (e.g., “five or fewer;” “five or less” refer to a range of numbers lower than a preceding stated number, and includes, for example, four or less, three or less, two or less, etc. The term “one or more but less than a higher number,” “two or more but less than a higher number,” “three or more but less than a higher number,” “four or more but less than a higher number,” “five or more but less than a higher number,” “six or more but less than a higher number,” “seven or more but less than a higher number,” “eight or more but less than a higher number,” “nine or more but less than a higher number,” “ten or more but less than a higher number,” “eleven or more but less than a higher number,” “twelve or more but less than a higher number,” “thirteen or more but less than a higher number,” “fourteen or more but less than a higher number,” or “fifteen or more but less than a higher number” is not limited to the stated higher number, but is inclusive of any integer or fractional value less than the higher number. For example, the statement “1 or more but less than 50,” encompasses “1 or more but less than 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 32, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3 or 2,” and fractions therebetween. PATENT Attorney Docket No: EXCT-42343.601 The term “sample” is used in its broadest sense. In one sense, it refers to a specimen or culture obtained from any source, as well as biological and environmental samples, including without limitation one or more of: human or animal tissues, bone marrow, plants, plant parts and extracts, fungi, microorganisms, fossil or mummified specimens, soil samples, sewage sludge, wastewater, stool or feces, or foodstuffs. For example, biological samples may be obtained from plants or animals (including humans) and encompass, e.g., fluids, solids, tissues, and gases. Human and animal samples include but are not limited to stool, tissue, sputum, mucus, blood or a blood product selected from plasma, serum, whole blood, an organ excretion such as pancreatic fluid, and urine. Environmental samples include environmental material such as soil, sediment, sludge, decomposing biological matter, archaeological remains, peat bogs, compost and water that are terrestrial or subterranean or marine in origin. These examples are not to be construed as limiting the sample types applicable to the present invention. As used herein in reference to samples, the term “a sample” collected from a source or subject, e.g., from a subject or environmental locale, is not limited to a single physical specimen but also encompasses a sample that is collected in multiple portions, e.g., “a sample” of blood may be collected in two, three, four or more different blood collection tubes or other blood collection devices (e.g., bags), or combinations of different blood collection devices, and a “sample” of soil or wastewater may be collected in two, three, four or more different specimen containers, e.g., test tubes, cups, bags, etc. As used herein, the term “fluid” refers to an amorphous liquid composition that is capable of flowing and of taking the shape of a container. A “fluid fraction,” as used in reference to a sample refers to a portion of a sample that is fluid. In certain embodiments, a sample comprising fluids and solids is partitioned, e.g., by filtration or centrifugation, such that the fluid fraction is separable from the solids, e.g., as a filtrate or a supernatant. As used herein in reference to samples, the terms “solid” or “solids” refer to materials that have at least some structural rigidity, e.g., an ability to hold their shape in the absence of external forces. Solids encompass true solids that are rigid or hard, and semisolids, which may deform or flow in response to force or pressure, but which do not flow in the absence of an external pressure. PATENT Attorney Docket No: EXCT-42343.601 The term “soil” as used herein refers to environmental samples of soil, sediment, manure, compost, and the like, e.g., commercial potting mixtures, commercial soil amendments. The term also includes a broad range of organic carbon and nitrogen content and varying sand, silt and / or clay compositions. “Soil” includes any composition containing components commonly associated with habitable and uninhabitable areas of the earth and space, including for example varying descriptions, e.g., indoor dust, outdoor dust, dirt, mud, muck, silt, ground, compost, composting landfills at various depths. Examples of soil samples include but are not limited to landfill (e.g., 0-3 inches deep or 3-6 inches deep); late-stage compost; coffee compost; marine sediment; lake sediment; mud sediment; animal manure (e.g., horse manure); mulch, e.g., mulch topsoil; the ocean floor, hillsides, mountaintops and may extend from the surface to any depth. The sample may be collected by any means using any commercially available or improvised method and tested directly. In one aspect, nucleic acid is extracted using a kit or method of the invention at the site of collection, or the sample may be stored before a nucleic acid is isolated therefrom. As used herein, the terms “environmental” and “environmental sample” include any environmental material, e.g., material contained in the earth and space, including space dust, airborne and waterborne locations and will include any organism, structure, and component considered alive, dead, dormant or inactive, whole, complete, undecaying and decaying that contains nucleic acid. “Environmental” and “environmental sample” include material and organisms that may be isolated from the environment as dust or suspended material collected by filtration or centrifugation. In some cases, the sample may comprise a liquid, fluent particulate solid, or fluid suspension of solid particles. In some cases, the sample may be processed prior to the analysis described herein. For example, the sample may be separated or purified from its source prior to analysis. In a particular example, the source is a mammalian (e.g., human) bodily substance (e.g., bodily fluid, blood such as whole blood, buffy coat, serum, plasma, urine, saliva, sweat, sputum, semen, mucus, lacrimal fluid, lymph fluid, amniotic fluid, interstitial fluid, cerebrospinal fluid, feces, tissue, organ, one or more dried blood spots, or the like). The sample may be a liquid sample or a liquid extract of a solid sample. In some embodiments, the source of the sample may be an organ or tissue, such as a biopsy sample and / or an endoscopic brushing sample (e.g., PATENT Attorney Docket No: EXCT-42343.601 endoscopic esophageal brushing sample), which may be solubilized by tissue disintegration / cell lysis. Samples can be obtained by any number of methodologies. Cell free or substantially cell free samples can be obtained by subjecting the sample to various techniques including, but not limited to, centrifugation and filtration. In some embodiments, nucleic acid is isolated from a sample (e.g., a tissue sample, a blood sample, a plasma sample, a serum sample, a whole blood sample, a buffy coat sample, a secretion sample, an organ secretion sample, a cerebrospinal fluid (CSF) sample, a saliva sample, a urine sample, and / or a stool sample) using direct gene capture, e.g., as detailed in U.S. Pat. Nos.8,808,990 and 9,169,511, and in WO 2012 / 155072, or by a related method. As used herein, dilution ratio as used in reference to a dispersed sample refers to an amount of a dispersing fluid combined with an amount of sample in a dispersed sample, e.g., an homogenate. In some embodiments, a dilution ratio is described as a volume of dispersing fluid to a volume of sample material (e.g., milliliters:milliliters or mL:mL). The term “v:v” refers to a volume-to-volume ratio. In some embodiments, the measure of a solid or semisolid sample of particular weight or mass is described in fluid units, e.g., treating 1 gram and 1 milliliter as equivalent portions of a sample. In some embodiments, a dilution ratio is described as volume of dispersing fluid to a mass or weight of a sample (e.g., milliliters:grams or mL:g). The terms “v:w” and “w:v” refer to ratios of volume-to-weight and weight-to-volume, respectively. As used herein, the terms “recovery” and “recovered” as used in reference to analytes, e.g., nucleic acids, proteins, etc., is used interchangeably with “obtaining” and “obtained,” for example, in describing analytes prepared or extracted from a sample. As used herein, the terms “suspected of comprising” or “suspected of containing” are used interchangeably to describe a feature that may or may not be present, e.g., a sample or subject, etc., that may or may not comprise or contain a particular feature, e.g., a marker nucleic acid, a target or a combination of targets (e.g., nucleic acids), or any other material or feature. As used herein, the terms “interfering compound” and “interfering substance” are used interchangeably to refer to components of a sample or fluid from a sample that interfere with manipulations of nucleic acids, e.g., with any step of extracting nucleic acid from a sample, or with any step of using extracted nucleic acid, e.g., in a nucleic acid detection assay or in any PATENT Attorney Docket No: EXCT-42343.601 operation using the nucleic acids, e.g., in combination with nucleic acid modifying enzymes that may be inhibited by the presence of the interfering compound. Interfering compounds include but are not limited to polyphenols, polysaccharides, humic substances, enzymatic inhibitors from soil, humic polymers, organic compounds from compost, decomposing plant materials, plant pigments, plant cell walls, chitins, photosynthetic pigments, humic acids, fulvic acids, phenolic polymers and / or phenolic oligomers, tannins, humics, and phenolic compounds. As used herein, the term “inhibitor” as used in reference to an assay, refers to a component or compound that inhibits any aspect or function of the assay, e.g., an enzymatic assay. For example, organic compounds such as bile salts, urea, phenolic compounds, ethanol, polysaccharides, sodium dodecyl sulfate (SDS), humic acids, tannic acid, and melanin, as well as different proteins, such as collagen, myoglobin, hemoglobin, lactoferrin, immunoglobin G (IgG) and proteinases can exhibit inhibiting effects on amplification assays such as polymerase chain reaction. Humic acids and phenolic compounds, common in soil and stool samples, e.g., have been reported to inhibit restriction endonucleases and Taq polymerase, the key enzyme of PCR, and may also decrease efficiencies in DNA-DNA hybridizations. See, e.g., Rossen, L., et al., (1992), Int J Food Microbiol 17, 37–45 (1992); Rådström et al. (2004), Mol Biotechnol 26, 133– 146; Schrader, C., et al. (2012), J. Appl. Microbiol.113(5):1014-1026); and WO 2006 / 073472, each of which is incorporated herein by reference in its entirety for all purposes. As used herein, the term “adsorb” and variants thereof (e.g., adsorbent, adsorbing, adsorbed) refers broadly to a non-covalent binding property of a component or material typically on the surface of the component or material, that serves to bind or stick to a second component or material, e.g., an adsorbent particle used to bind nucleic acid. The terms are used without limitation to the permanence or reversibility of the binding property. As used herein, binding of a second component on an internal surface of an adsorbant material, e.g., in a pore of a particle or other solid support, is encompassed in the meaning of “adsorb.” As used herein, the term “sorbent” and variants thereof refer broadly to a property of a component or material to bind or take up another material or substance, e.g., by adsorption or absorption. “Desorb” and “desorption” refer to the release or separation of adsorbed or absorbed material from the sorbent component or material. PATENT Attorney Docket No: EXCT-42343.601 As used herein, the terms “patient” or “subject” refer to organisms to be subject to various tests provided by the technology. The term “subject” includes animals, preferably mammals, including humans. In a preferred embodiment, the subject is a primate. In an even more preferred embodiment, the subject is a human. Further with respect to diagnostic methods, a preferred subject is a vertebrate subject. A preferred vertebrate is warm-blooded; a preferred warm-blooded vertebrate is a mammal. A preferred mammal is most preferably a human. As used herein, the term “subject' includes both human and animal subjects. Thus, veterinary diagnostic uses are provided herein. As such, the present technology provides for the diagnosis of mammals such as humans, as well as those mammals of importance due to being endangered, such as Siberian tigers; of economic importance, such as animals raised on farms for consumption by humans; and / or animals of social importance to humans, such as animals kept as pets or in zoos. Examples of such animals include but are not limited to: carnivores such as cats and dogs; swine, including pigs, hogs, and wild boars; ruminants and / or ungulates such as cattle, oxen, sheep, giraffes, deer, goats, bison, and camels; pinnipeds; and horses. Thus, also provided is the diagnosis and treatment of livestock, including, but not limited to, domesticated swine, ruminants, ungulates, horses (including racehorses), and the like. The presently-disclosed subject matter further includes a system for diagnosing cancer in a subject. The system can be provided, for example, as a commercial kit that can be used to screen for a risk of cancer or diagnose a cancer in a subject from whom a biological sample has been collected. An exemplary system provided in accordance with the present technology includes assessing the methylation state of a marker described herein. As used herein, the term “cell sample” refers to a sample that comprises a cell (e.g., an intact cell from a subject) or cellular material (e.g., material from cells from the subject that are not intact cells). As used herein, the term “dispersed sample” refers to a sample in which some or all of a non-fluid fraction of the sample is dispersed or suspended in a fluid medium. A sample may be dispersed, for example, by stirring, vortexing, shaking, blending, sonicating, extruding, or any manner that disrupts or disperses a sample, e.g., in a dispersing fluid, to a degree suitable for a particular purpose. In some embodiments, a dispersed sample is naturally occurring, e.g., as a bodily fluid such as urine, saliva, or blood, or as an environmental sample, such as wastewater. PATENT Attorney Docket No: EXCT-42343.601 As used herein, the term “dispersing fluid,” and “homogenizing fluid” as used in reference to a dispersed sample refers to a fluid medium in which a sample is dispersed, e.g., by homogenization. By way of example and not limitation, a dispersing fluid may be part of a fluid sample (e.g., the fluid components of urine, blood, wastewater, etc.) or may be added to a sample, e.g., stool or soil, to aid in dispersing the sample. Dispersing fluids added to the sample may comprise components that facilitate dispersion or downstream processing or analysis, and may comprise, for example, one or more of a chaotropic compound; an alcohol; a detergent or surfactant (e.g., IGEPAL, Tween 20 detergent, etc.); a salt; a preservative; a buffering agent; a protein; a protoporphyrin IX complex; a nuclease inhibitor (e.g., an RNase inhibitor or DNase inhibitor), and a nuclease (e.g., an RNase or DNase). See, e.g., WO2019 / 190787; US10,702,250; WO2021 / 076969; each of which is incorporated by reference herein in its entirety for all purposes. Detergents may, e.g., comprise one or more of anionic agents, cationic agents, non- ionic agents, zwitterionic agents, and mixtures of detergent agents. Solutions used in the technology, e.g., dispersing fluids, silica binding solutions, elution solutions, etc., may have the same or different pHs, and are not limited to a particular pH or pH range. Any of the solutions used may, for example, have a pH from about 2 to 10, preferably from about 7-9, more preferably from about 7-8. In some embodiments, the pH of a solution is from about 2, 3, 4, 5, 6, or 7 to about 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11. As used herein the term “homogenizing” refers to a process for breaking up or disrupting material, e.g., sample material, preferably in a fluid medium, e.g., a buffer or other solution to produce a dispersed sample. Homogenizing may be performed by stirring, vortexing, shaking, blending, sonicating, or any manner that disrupts or disperses a sample to a degree suitable for a particular purpose. In some embodiments, homogenization beads (e.g., steel, glass, or garnet beads) are used in conjunction with mixing to facilitate sample disruption. As used herein, “homogenizing” a sample does not require that the entirety of a sample, e.g., a solid or semisolid sample, be dispersed completely or uniformly, e.g., within a fluid medium. With some sample types, for example, portions of the sample may be readily dissolved or suspended, while other portions of a sample may remain undispersed after vigorous shaking or mixing. As used herein, the term “homogenate” refers to the composition produced by homogenizing. PATENT Attorney Docket No: EXCT-42343.601 As used herein, the term “fluid sample” is used interchangeably with the term “liquid sample,” and refers to a sample having the properties of a fluid, as set forth above. In certain embodiments, a fluid sample has, or has been treated to have, a reduced amount of, or to be substantially free of suspended solids or particulates, e.g., insoluble materials, such as cell debris, soil particles, precipitants, etc. In other embodiments, a fluid sample comprises a mixture of liquids and solids that are combined in amounts to have the properties of a fluid, e.g., a fluid homogenate or suspension of a sample dispersed in a dispersing fluid. As used herein, the terms “supernatant,” “clarified supernatant,” and “clarified fluid sample” are used interchangeably to refer to a fluid fraction of a composition, e.g., a sample, that is separated from any non-fluid fraction of the composition, e.g., by centrifugation, pressing, filtration, straining, draining, etc., and encompasses filtrates produced by filtration of a sample. In some embodiments, the fluid fraction comprises fluids that are part of the original sample (e.g., fluids from blood, urine, mud, wastewater, etc.) and in some embodiments, the fluid fraction may comprise a fluid added during sample processing, e.g., a dispersing fluid added to a solid or semisolid sample (e.g., stool or soil) prior to mixing or homogenization. A “non-fluid fraction” refers to residual material from which a clarified supernatant or fluid fraction is, or has been, separated, and may comprise, for example, insoluble materials from the sample (e.g., undispersed tissue, particles, fibers, etc.) and / or insoluble non-sample materials (e.g., beads, precipitates, flocculants, and / or other materials formed from a composition added to the sample prior to collection of the clarified supernatant). As used herein, the term “pre-treated” as used in reference to a fluid sample, e.g., a fluid fraction or clarified supernatant, refers to a fluid sample that has been treated with an adsorption matrix, e.g., a silica matrix, in a binding solution wherein at least one interfering compound, if present in the fluid sample, is bound to the adsorption matrix to remove the bound interfering compound. As used herein, the terms “chaotrope,” “chaotropic agent” and “chaotropic substance” are used interchangeably to refer to a molecule or composition that exhibit chaotropic properties, e.g., disrupting hydrogen bonding and other non-covalent macromolecular interactions. Preferred chaotropic agents include guanidinium hydrochloride (“GHC”), and thiocyanates, isothiocyanates and / or perchlorates, in particular guanidinium thiocyanate (“GTC”) or guanidinium isothiocyanate (GITC”). PATENT Attorney Docket No: EXCT-42343.601 In reference to alcohols as used in combination with chaotropic agents, preference is given to employing short-chain branched or unbranched alkanols having from 1 to 5 carbon atoms, such as methanol, ethanol, propanol, isopropanol, butanols or pentanols, or mixtures thereof. In particularly preferred embodiments, isopropanol or an alcohol or alcohol mixture having isopropanol-like properties is employed. See, e.g., US Pat. No.9,809,612 (Ritt). As used herein, the terms “silica particle” and “silica adsorption matrix” refer broadly to solid phase silicon-containing materials that exhibit suitable hydrophilic and electropositive characteristics for binding nucleic acids in the presence of chaotropic agents, with or without alcohols. Preferred silicon-containing materials include SiO2 crystals and other forms of silicon oxide, skeletons of diatoms built up from SiO2, amorphous silicon oxide and glass powder, silica gel, glass, zeolite, and silica-coated beads or particles, e.g., paramagnetic particles, boron silicates, aluminum silicates, phosphosilicates, silica carbonyl, silica sulfonyl and silica phosphonyl. See, e.g., US Pat. Nos.5,234,809 (Boom); 5,503,816 (Woodard); 7,459,548 (Brolaski); and 9,809,612 (Ritt), each of which is incorporated herein by reference in its entirety for all purposes. As used herein in reference to binding materials, the terms “particles” and “beads” are used interchangeably, and refer to small diameter solid materials, preferably between about 5 nm and 1 mm in average diameter. As used herein, a “methylation state,” “methylation profile,” and “methylation status” of a nucleic acid molecule refers to the presence or absence of one or more methylated nucleobases in the nucleic acid molecule. For example, a nucleic acid molecule containing a methylated cytosine is considered methylated (e.g., the methylation state of the nucleic acid molecule is methylated). A nucleic acid molecule that does not contain any methylated nucleotides is generally considered unmethylated. The methylation state of a particular nucleic acid sequence (e.g., a gene marker or region of a gene marker) can indicate the methylation state of every base in the sequence or can indicate the methylation state of a subset of the bases (e.g., of one or more cytosines) within the sequence, or can indicate information regarding regional methylation density within the sequence with or without providing precise information of the locations within the sequence that the methylation occurs. As such, the methylation state describes the state of methylation of a nucleic acid (e.g., a genomic sequence). In addition, the methylation state refers to the characteristics of a nucleic PATENT Attorney Docket No: EXCT-42343.601 acid segment at a particular genomic locus relevant to methylation. Such characteristics include, but are not limited to, whether any of the cytosine (C) residues within this DNA sequence are methylated, the location of methylated C residue(s), the frequency or percentage of methylated C throughout any particular region of a nucleic acid, and allelic differences in methylation due to, e.g., difference in the origin of the alleles. The term “next generation sequencing” refers to highly parallelized methods of performing nucleic acid sequencing and comprises the sequencing-by-synthesis or sequencing- by-ligation platforms (e.g., employed by Illumina, Life Technologies, Pacific Biosciences and Roche, etc.). Next generation sequencing methods may also include, but not be limited to, nanopore sequencing methods such as offered by Oxford Nanopore or electronic detection-based methods such as the Ion Torrent technology commercialized by Life Technologies. As used herein, a “nucleic acid” or “nucleic acid molecule” generally refers to any ribonucleic acid or deoxyribonucleic acid, which may be unmodified or modified DNA or RNA. “Nucleic acids” include, without limitation, single- and double-stranded nucleic acids. As used herein, the term “nucleic acid” also includes DNA as described above that contains one or more modified bases. Thus, DNA with a backbone modified for stability or for other reasons is a “nucleic acid.” The term “nucleic acid” as it is used herein embraces such chemically, enzymatically, or metabolically modified forms of nucleic acids, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including for example, simple and complex cells. In some embodiments of the technology, nucleic acid is detected and / or isolated from one or more organisms present in a sample, e.g., a soil sample, examples of which include but are not limited to bacteria (e.g., Gram positive or Gram negative), yeast, fungi, algae, viruses (e.g., HIV) and nematodes. Nucleic acids can be from any organism, including, but not limited to viruses, bacteriophage, plasmids, spores, yeast, fungi, algae, nematodes, protozoa, eukaryotic cells, prokaryotic cells and in general, single- and multicellular forms. DNA or RNA detected or isolated using a kit or method of the technology is not necessarily located within a specific organelle among prokaryotic members, but may be found in the cytoplasm, chloroplasts, mitochondria, and nuclei of eukaryotic and multicellular organisms. RNA detected or isolated using a kit or method of the technology is found in a variety of organisms, including, but not limited to viruses, eukaryotic cells, prokaryotic cells and in general, single- and multicellular PATENT Attorney Docket No: EXCT-42343.601 forms. RNA detected or isolated using a kit or method of the invention includes forms found in a multitude of biological forms, including but not limited to, messenger RNA in protein translation, ribosomal RNA in ribosomal protein translation, transfer RNA in protein translation, small interfering RNA and microRNA in gene regulation. Nucleic acids may also be extracellular, i.e., nucleic acids in a sample, e.g., a soil sample, fecal sample, blood sample, etc., may be outside of the cell in which they were produced by replication or transcription. As used herein, “cell-free” as used in reference to a nucleic acid, e.g., DNA or RNA (“cfDNA; cfRNA” refers to nucleic acids found, e.g., in a sample, that are not contained in a cell in the sample). For example, many samples, including e.g., blood, feces, urine, used culture media, and soil typically comprise cell-free nucleic acids, e.g., from the death or decay of cells and microbes in or proximal to the material sampled. As used herein, the terms “circulating tumor DNA” (or “ctDNA”) is tumor-derived DNA that is circulating in the peripheral blood of a patient. ctDNA is of tumor origin and originates directly from the tumor or from circulating tumor cells (CTCs), which are viable, intact tumor cells that shed from primary tumors and enter the bloodstream or lymphatic system. Likewise, circulating RNA originating from a tumor is referred to as “ctRNA.” The terms as used herein with respect to nucleic acid extracted from a sample refer to the nature and location of the nucleic acid prior to collection of the sample and prior to extraction of the nucleic acid from the sample. The terms “oligonucleotide” or “polynucleotide” or “nucleic acid” refer to a molecule having two or more deoxyribonucleotides or ribonucleotides, preferably more than three, and usually more than ten. The exact size will depend on many factors, which in turn depends on the ultimate function or use of the oligonucleotide. The oligonucleotide may be generated in any manner, including chemical synthesis, DNA replication, reverse transcription, or a combination thereof. Typical deoxyribonucleotides for DNA are thymine, adenine, cytosine, and guanine. Typical ribonucleotides for RNA are uracil, adenine, cytosine, and guanine. As used herein, the terms “locus” or “region” of a nucleic acid refer to a subregion of a nucleic acid, e.g., a gene on a chromosome, a single nucleotide, etc. PATENT Attorney Docket No: EXCT-42343.601 The term “marker,” as used herein, refers to a substance (e.g., a nucleic acid, or a region of a nucleic acid, or a protein) that may be used to distinguish non-normal cells (e.g., cancer cells) from normal cells, e.g., based on presence, absence, or status (e.g., post-transcriptional processing) of the marker substance. The term “analyte” as used herein in reference to characterizing a material, e.g., a biological sample, refers to any constituent of the material or sample, e.g., biomolecules, organic or inorganic chemicals, etc., for which the material or sample is being analyzed. The term “selectively removing” as used herein in reference to a process of removing a constituent or component from a sample, e.g., an interfering compound, a process that preferentially removes one constituent as compared to other constituents in the process. As used herein, the “sensitivity” of a given marker (or set of markers used together) refers to the percentage of samples that report a marker value (e.g., an expression marker) above a threshold value that distinguishes between neoplastic and non-neoplastic samples. In some embodiments, a positive is defined as a histology-confirmed neoplasia that reports a marker value above a threshold value (e.g., the range associated with disease), and a false negative is defined as a histology-confirmed neoplasia that reports a marker value below the threshold value (e.g., the range associated with no disease). The value of sensitivity, therefore, reflects the probability that a measurement for a given marker obtained from a known diseased sample will be in the range of disease-associated measurements. As defined here, the clinical relevance of the calculated sensitivity value represents an estimation of the probability that a given marker would detect the presence of a clinical condition when applied to a subject with that condition. As used herein, the “specificity” of a given marker (or set of markers used together) refers to the percentage of non-neoplastic samples that report a marker value (e.g., an expression marker) below a threshold value that distinguishes between neoplastic and non-neoplastic samples. In some embodiments, a negative is defined as a histology-confirmed non-neoplastic sample that reports a marker value below the threshold value (e.g., the range associated with no disease), and a false positive is defined as a histology-confirmed non-neoplastic sample that reports a marker value above the threshold value (e.g., the range associated with disease). The value of specificity, therefore, reflects the probability that a marker measurement for a given marker obtained from a known non-neoplastic sample will be in the range of non-disease PATENT Attorney Docket No: EXCT-42343.601 associated measurements. As defined here, the clinical relevance of the calculated specificity value represents an estimation of the probability that a given marker would detect the absence of a clinical condition when applied to a patient without that condition. As used herein, the term “peripheral blood” refers to the circulating blood of the body. As used herein, a “methylation-specific reagent” refers to a reagent that modifies a nucleotide of the nucleic acid molecule as a function of the methylation state of the nucleic acid molecule. In particular embodiments the term refers to a compound or composition or other agent or collection or sequence thereof that can change the nucleotide sequence of a nucleic acid molecule in a manner that reflects the methylation state of the nucleic acid molecule. Methods of treating a nucleic acid molecule with such reagents can include contacting the nucleic acid molecule with the reagent, coupled with additional steps, if desired, to accomplish the desired change of nucleotide sequence. Such methods can be applied in a manner in which unmethylated nucleotides (e.g., each unmethylated cytosine) are modified to a different nucleotide. For example, in some embodiments, such a reagent can deaminate unmethylated cytosine nucleotides to produce deoxy uracil residues. An exemplary reagent is a bisulfite reagent. In addition, treatment with a “methylation-specific reagent” can be applied in a manner in which methylated nucleotides are modified to a different nucleotide. For example, methylated cytosines (including 5mC and 5hmC) in DNA can be converted by combining oxidation by ten- eleven translocation (TET) family dioxygenases with reduction by borane derivatives (e.g., pyridine borane and 2-picoline borane (pic-BH3)), in a process referred to herein as TAPS (TET Assisted Pyridine borane Sequencing). See, e.g., the TAPS method combining oxidation by TET enzymes with reduction by borane derivatives, described, e.g., in US 2020 / 0370114 A1, Application Ser. No.16 / 960,510, filed July 7, 2020, which is incorporated herein by reference for all purposes. In embodiments of the TAPS method, methylated cytosines are converted to dihydro uracil. Other methods of converting methylated Cs include, for example: Sequencing Method Cytosine Method of Analysis PATENT Attorney Docket No: EXCT-42343.601 TET-assisted bisulfite 5hmC Enzymatic treatment with sequencing (TAB-seq) T4-BGT then TET followed b bi lfit t t t h See, e.g., Loise Williams, et al., Enzymatic Methyl-seq: The next generation of methylome analysis, New England Biolabs Expressions 2019. Feature Article., incorporated by reference in its entirety, for all purposes. In preferred embodiments, methylation-specific reagents modify one nucleotide of the four typically-occurring nucleotides in a nucleic acid molecule (C, G, T, and A for DNA and C, G, U, and A for RNA), such that the reagent modifies the one nucleotide without modifying the other three nucleotides. The nucleotides resulting from conversion are not limited to the four typically occurring nucleotides listed above, and may include, for example, modified or variant forms of purine or pyrimidine structures, including, e.g., nucleobase analogs discussed herein. In preferred embodiments, the nucleotides produced by conversion are recognized by DNA modifying enzymes, e.g., DNA polymerases, as one of the typically occurring nucleotides listed above, and can serve as templates for strand replication. Conversion of nucleotides by any of the methods described herein may be detected by determining the sequence of a resulting strand, e.g., using standard sequencing methods, or by interrogating single or a few specific nucleotide locations to determine the identity of the nucleobase at the select locations. As used herein, the term “converted” as used in reference to a nucleotide or DNA strand refers to a nucleotide or DNA strand that has been treated with a reagent or reagents under conditions in which some nucleotides are converted into other nucleotides. For example, in bisulfite conversion, cytosine bases in the DNA are typically deaminated, resulting in uracil bases at converted loci. While inefficient, bisulfite can also cause deamination of 5-methyl cytosine bases, resulting in thymine bases at converted loci. “Bisulfite-treated” and bisulfite- converted” are used interchangeably herein in reference to DNA or nucleotide loci that have PATENT Attorney Docket No: EXCT-42343.601 been exposed to a bisulfite reagent under conditions in which cytosine is typically converted to uracil. In the bisulfite-free TAPS process, methylated cytosines are selectively converted to dihydrouracil (DHU), while unmethylated Cs are not converted. The DHU nucleotides base pair with A nucleotides rather than G nucleotides, making them readily distinguishable from the unmethylated C bases in the converted DNA strands. The term “bisulfite reagent” refers to a reagent comprising bisulfite, disulfite, hydrogen sulfite, or combinations thereof, useful as disclosed herein to distinguish between methylated and unmethylated CpG dinucleotide sequences. Methods of said treatment are known in the art (e.g., PCT / EP2004 / 011715 and WO 2013 / 116375, each of which is incorporated by reference in its entirety). In some embodiments, bisulfite treatment is conducted in the presence of denaturing solvents such as but not limited to n-alkyleneglycol or diethylene glycol dimethyl ether (DME), or in the presence of dioxane or dioxane derivatives. In some embodiments the denaturing solvents are used in concentrations between 1% and 35% (v / v). In some embodiments, the bisulfite reaction is carried out in the presence of scavengers such as but not limited to chromane derivatives, e.g., 6-hydroxy-2,5,7,8,-tetramethylchromane 2-carboxylic acid or trihydroxybenzone acid and derivatives thereof, e.g., Gallic acid (see: PCT / EP2004 / 011715, which is incorporated by reference in its entirety). In certain preferred embodiments, the bisulfite reaction comprises treatment with ammonium hydrogen sulfite, also referred to as ammonium bisulfite, e.g., as described in WO 2013 / 116375. The term “methylation assay” refers to any assay for determining the methylation state of one or more CpG dinucleotide sequences within a sequence of a nucleic acid. The term “primer” refers to an oligonucleotide, whether occurring naturally as, e.g., a nucleic acid fragment from a restriction digest, or produced synthetically, that is capable of acting as a point of initiation of synthesis when placed under conditions in which synthesis of a primer extension product that is complementary to a nucleic acid template strand is induced, (e.g., in the presence of nucleotides and an inducing agent such as a DNA polymerase, and at a suitable temperature and pH). The primer is preferably single stranded for maximum efficiency in amplification, but may alternatively be double stranded. If double stranded, the primer is first treated to separate its strands before being used to prepare extension products. Preferably, the primer is an oligodeoxyribonucleotide. The primer must be sufficiently long to prime the PATENT Attorney Docket No: EXCT-42343.601 synthesis of extension products in the presence of the inducing agent. The exact lengths of the primers will depend on many factors, including temperature, source of primer, and the use of the method. The term “probe” refers to an oligonucleotide (e.g., a sequence of nucleotides), whether occurring naturally as in a purified restriction digest or produced synthetically, recombinantly, or by PCR amplification, that is capable of hybridizing to another oligonucleotide of interest. A probe may be single-stranded or double-stranded. Probes are useful in the detection, identification, and isolation of particular gene sequences (e.g., a “capture probe”). It is contemplated that any probe used in the present invention may, in some embodiments, be labeled with any “reporter molecule,” so that it is detectable in any detection system, including, but not limited to enzyme (e.g., ELISA, as well as enzyme-based histochemical assays), fluorescent, radioactive, and luminescent systems. It is not intended that the present invention be limited to any particular detection system or label. The term “target,” as used herein refers to an analyte such as a nucleic acid or protein sought to be sorted out from other nucleic acids or proteins, e.g., by probe binding, amplification, isolation, capture, etc. For example, when used in reference to the polymerase chain reaction, “target” refers to the region of nucleic acid bounded by the primers used for polymerase chain reaction, while when used in an assay in which target nucleic acid is not amplified, e.g., in some embodiments of an invasive cleavage assay, a target comprises the site at which a probe and invasive oligonucleotides (e.g., INVADER oligonucleotide) bind to form an invasive cleavage structure, such that the presence of the target nucleic acid can be detected. A “segment” is defined as a region of nucleic acid within the target sequence. As used in reference to a double- stranded nucleic acid, the term “target” is not limited to a particular strand of the duplexed target, e.g., a coding strand, but may be used in reference to either one or both strands of, for example, a double-stranded gene or reference DNA. The term “purified” refers to molecules, either nucleic acid or amino acid molecules, or other biomolecules that are removed from an environment, e.g., their natural environment, or an environment in which they have been produced (e.g., recombinantly or in an in vitro enzymatic reaction), or from a sample. As used herein, the terms “extract / extracted,” “isolate / isolated,” and “purify / purified,” when used in relation to a preparation of nucleic acid (or other molecules), as PATENT Attorney Docket No: EXCT-42343.601 in “extracted nucleic acids” or “purified cell-free nucleic acids” (or other molecules), are used interchangeably. A preparation of “isolated nucleic acid” may therefore be a purified or extracted nucleic acid, and may be a single species of nucleic acid (e.g., a molecule captured using a complementary oligonucleotide) or it may refer to total nucleic acid isolated from a sample, or it may refer to one form of nucleic acid fractionated from another form of nucleic acid, e.g., RNA separated from DNA, e.g., by use of DNase during a processing step. “Substantially purified” molecules are at least 60% free, preferably at least 75% free, and more preferably at least 90% free from other components with which they are associated in the pre-purification environment. As used herein, the terms “purified” or “to purify” also refer to the removal of contaminants or any unwanted constituents from a sample. The term “amplifying” or “amplification” in the context of nucleic acids refers to the production of multiple copies of a polynucleotide, or a portion of the polynucleotide, typically starting from a small amount of the polynucleotide (e.g., a single polynucleotide molecule), where the amplification products or amplicons are generally detectable. Amplification of polynucleotides encompasses a variety of chemical and enzymatic processes. The generation of multiple nucleic acid copies from one or a few copies of a target or template nucleic acid molecule during a polymerase chain reaction (PCR) or a ligase chain reaction (LCR; see, e.g., U.S. Patent No.5,494,810; herein incorporated by reference in its entirety) are forms of amplification. Additional types of amplification include, but are not limited to, allele-specific PCR (see, e.g., U.S. Patent No.5,639,611; herein incorporated by reference in its entirety), assembly PCR (see, e.g., U.S. Patent No.5,965,408; herein incorporated by reference in its entirety), helicase-dependent amplification (see, e.g., U.S. Patent No.7,662,594; herein incorporated by reference in its entirety), hot-start PCR (see, e.g., U.S. Patent Nos.5,773,258 and 5,338,671; each herein incorporated by reference in their entireties), intersequence-specific PCR, inverse PCR (see, e.g., Triglia, et al.(1988) Nucleic Acids Res., 16:8186; herein incorporated by reference in its entirety), ligation-mediated PCR (see, e.g., Guilfoyle, R. et al., Nucleic Acids Research, 25:1854-1858 (1997); U.S. Patent No.5,508,169; each of which are herein incorporated by reference in their entireties), miniprimer PCR, multiplex ligation-dependent probe amplification (see, e.g., Schouten, et al., (2002) Nucleic Acids Research 30(12): e57; herein incorporated by reference in its entirety), multiplex PCR (see, e.g., Chamberlain, et al., PATENT Attorney Docket No: EXCT-42343.601 (1988) Nucleic Acids Research 16(23) 11141-11156; Ballabio, et al., (1990) Human Genetics 84(6) 571-573; Hayden, et al., (2008) BMC Genetics 9:80; each of which are herein incorporated by reference in their entireties), nested PCR, overlap-extension PCR (see, e.g., Higuchi, et al., (1988) Nucleic Acids Research 16(15) 7351-7367; herein incorporated by reference in its entirety), real time PCR (see, e.g., Higuchi, et al., (1992) Biotechnology 10:413-417; Higuchi, et al., (1993) Biotechnology 11:1026-1030; each of which are herein incorporated by reference in their entireties), reverse transcription PCR (see, e.g., Bustin, S.A. (2000) J. Molecular Endocrinology 25:169-193; herein incorporated by reference in its entirety), solid phase PCR, thermal asymmetric interlaced PCR, and Touchdown PCR (see, e.g., Don, et al., Nucleic Acids Research (1991) 19(14) 4008; Roux, K. (1994) Biotechniques 16(5) 812-814; Hecker, et al., (1996) Biotechniques 20(3) 478-485; each of which are herein incorporated by reference in their entireties). Polynucleotide amplification also can be accomplished using digital PCR (see, e.g., Kalinina, et al., Nucleic Acids Research.25; 1999-2004, (1997); Vogelstein and Kinzler, Proc Natl Acad Sci USA.96; 9236-41, (1999); International Patent Publication No. WO05023091A2; US Patent Application Publication No.20070202525; each of which are incorporated herein by reference in their entireties). In some embodiments, a portion of a target nucleic acid is copied in the amplification, and in some embodiments, a non-target polynucleotide is amplified in response to the presence of a target nucleic acid, (e.g., a cleaved flap, ligation product, a rolling circle replication product, etc.) The term “polymerase chain reaction” (“PCR”) refers to the method of K.B. Mullis U.S. Patent Nos.4,683,195, 4,683,202, and 4,965,188, that describe a method for increasing the concentration of a segment of a target sequence in a mixture of genomic or other DNA or RNA, without cloning or purification. This process for amplifying the target sequence consists of introducing a large excess of two oligonucleotide primers to the DNA mixture containing the desired target sequence, followed by a precise sequence of thermal cycling in the presence of a DNA polymerase. The two primers are complementary to their respective strands of the double stranded target sequence. To effect amplification, the mixture is denatured, and the primers then annealed to their complementary sequences within the target molecule. Following annealing, the primers are extended with a polymerase so as to form a new pair of complementary strands. The steps of denaturation, primer annealing, and polymerase extension can be repeated many times (i.e., denaturation, annealing and extension constitute one “cycle;” there can be numerous PATENT Attorney Docket No: EXCT-42343.601 “cycles”) to obtain a high concentration of an amplified segment of the desired target sequence. The length of the amplified segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and therefore, this length is a controllable parameter. By virtue of the repeating aspect of the process, the method is referred to as the “polymerase chain reaction” (“PCR”). Because the desired amplified segments of the target sequence become the predominant sequences (in terms of concentration) in the mixture, they are said to be “PCR amplified” and are “PCR products” or “amplicons.” Those of skill in the art will understand the term “PCR” encompasses many variants of the originally described method using, e.g., real time PCR, nested PCR, reverse transcription PCR (RT-PCR), single primer and arbitrarily primed PCR, etc. As used herein, the term “nucleic acid detection assay” refers to any method of determining the nucleotide composition of a nucleic acid of interest. Nucleic acid detection assays include but are not limited to, DNA sequencing methods, probe hybridization methods, structure specific cleavage assays (e.g., the INVADER assay, (Hologic, Inc.) and are described, e.g., in U.S. Patent Nos.5,846,717, 5,985,557, 5,994,069, 6,001,567, 6,090,543, and 6,872,816; Lyamichev et al., Nat. Biotech., 17:292 (1999), Hall et al., PNAS, USA, 97:8272 (2000), and US 2009 / 0253142, each of which is herein incorporated by reference in its entirety for all purposes); enzyme mismatch cleavage methods (e.g., U.S. Pat. Nos.6,110,684, 5,958,692, 5,851,770, herein incorporated by reference in their entireties); polymerase chain reaction (PCR) (including real-time PCR, such as TaqmanTMPCR), described above; branched hybridization methods (e.g., Chiron, U.S. Pat. Nos.5,849,481, 5,710,264, 5,124,246, and 5,624,802, herein incorporated by reference in their entireties); rolling circle replication (e.g., U.S. Pat. Nos.6,210,884, 6,183,960 and 6,235,502, herein incorporated by reference in their entireties); NASBA (e.g., U.S. Pat. No. 5,409,818, herein incorporated by reference in its entirety); molecular beacon technology (e.g., U.S. Pat. No.6,150,097, herein incorporated by reference in its entirety); E-sensor technology (Motorola, U.S. Pat. Nos.6,248,229, 6,221,583, 6,013,170, and 6,063,573, herein incorporated by reference in their entireties); cycling probe technology (e.g., U.S. Pat. Nos.5,403,711, 5,011,769, and 5,660,988, herein incorporated by reference in their entireties); Dade Behring signal amplification methods (e.g., U.S. Pat. Nos.6,121,001, 6,110,677, 5,914,230, 5,882,867, and 5,792,614, herein incorporated by reference in their entireties); ligase chain reaction (e.g., Baranay Proc. Natl. Acad. Sci USA 88, 189-93 (1991)); and sandwich hybridization methods PATENT Attorney Docket No: EXCT-42343.601 (e.g., U.S. Pat. No.5,288,609, herein incorporated by reference in its entirety). Additional methods are described in U.S. Pat. Appl. Ser. No.15 / 881,409 of Allawi, et al., filed 01 / 26 / 2018, incorporated herein by reference in its entirety. In some embodiments, target nucleic acid is amplified (e.g., by polymerase chain reaction, e.g., as described by K.B. Mullis in U.S. Patent Nos.4,683,195, 4,683,202, and 4,965,188) and amplified nucleic acid is detected simultaneously using an invasive cleavage assay. Assays configured for performing a detection assay (e.g., invasive cleavage assay) in combination with an amplification assay are described in U.S. Pat. No.9,096,893, incorporated herein by reference in its entirety for all purposes. Additional amplification plus invasive cleavage detection configurations, termed the QuARTS method, are described in, e.g., in U.S. Pat. Nos.8,361,720; 8,715,937; 8,916,344; and 9,212,392, each of which is incorporated herein by reference for all purposes. Additional modified QuARTS methods, termed LQAS and TELQAS, are described in, e.g., U.S. Patent Publication No. US20200248233A1, U.S. Patent No.10,648,025, International Application Publication No. WO2021041726A1, and International Application publication No. WO2020206256A1, each of which is incorporated herein by reference for all purposes The term “invasive cleavage structure” as used herein refers to a cleavage structure comprising i) a target nucleic acid, ii) an upstream nucleic acid (e.g., an invasive or “INVADER” oligonucleotide), and iii) a downstream nucleic acid (e.g., a probe), where the upstream and downstream nucleic acids anneal to contiguous regions of the target nucleic acid, and where an overlap forms between a 3′ portion of the upstream nucleic acid and duplex formed between the downstream nucleic acid and the target nucleic acid. An overlap occurs where one or more bases from the upstream and downstream nucleic acids occupy the same position with respect to a target nucleic acid base, whether or not the overlapping base(s) of the upstream nucleic acid are complementary with the target nucleic acid, and whether or not those bases are natural bases or non-natural bases. In some embodiments, the 3′ portion of the upstream nucleic acid that overlaps with the downstream duplex is a non-base chemical moiety such as an aromatic ring structure, e.g., as disclosed, for example, in U.S. Pat. No.6,090,543, incorporated herein by reference in its entirety. In some embodiments, one or more of the nucleic acids may be attached to each other, e.g., through a covalent linkage such as nucleic acid stem-loop, or through a non- nucleic acid chemical linkage (e.g., a multi-carbon chain). As used herein, the term “flap PATENT Attorney Docket No: EXCT-42343.601 endonuclease assay” includes “INVADER” invasive cleavage assays, QuARTS assays, LQAS and TELQAS assays, as described above. A “flap oligonucleotide” refers to an oligonucleotide cleavable in a detection assay, such as an invasive cleavage assay, by a flap endonuclease. In preferred embodiments, a flap oligonucleotide forms an invasive cleavage structure with other nucleic acids, e.g., a target or template nucleic acid and an invasive oligonucleotide. Flap assay reagents may optionally contain a target or template nucleic acid to which an invasive oligonucleotide and flap oligonucleotide bind. In particularly preferred embodiments, flap assay reagents comprise a Mg++flap assay buffer, as discussed herein. As used herein, the term “flap endonuclease” refers to a structure-specific nucleolytic enzyme that cleaves a nucleic acid flap structure, e.g., an invasive cleavage structure. Flap endonucleases include, e.g., 5′ -exonuclease domains of the DNA polymerase I proteins of Eubacteria and the FEN-1 proteins of Eukarya and Archaea. (Kaiser, et al., supra). Flap endonucleases may cleave additional structures, e.g., pseudo-Y, 5′ overhang, and gap structures. See, e.g., Shen, B., BioEssays 27:717-729 (2005); Finger, LD., Subcell Biochem.62:301–326 (2012), and U.S. Patent Appl. Ser. No.62 / 901,085, filed September 16, 2019, each of which is incorporated herein in its entirety. As used herein the term “flap endonuclease substrate” refers to a nucleic acid flap structure, e.g., an invasive cleavage structure, that is recognized and cleaved by a flap endonuclease, such as a FEN-1 endonuclease. The term “FEN-1” as used herein in reference to an enzyme refers to a non-polymerase flap endonuclease from a eukaryote or archaeal organism, as encoded by a FEN-1 gene. See, e.g., Kaiser, et al., supra, WO 02 / 070755, and US Patent No. US 7,122,364, which are incorporated by reference herein in their entireties for all purposes. The term “FEN-1 activity” refers to any enzymatic activity of a FEN-1 enzyme. FEN-1 endonucleases also comprise modified FEN-1 proteins, e.g., chimerical proteins comprising portions of FEN-1 enzymes from different organisms, and enzymes comprising one or more mutations (e.g., substitutions, deletions, insertions, etc.), as described in WO 02 / 070755, and US Patent No. US 7,122,364. As used herein, the terms “flap endonuclease assay” “flap assay” refer to a detection assay in which formation and cleavage of a flap endonuclease substrate is used to evaluate a sample for the presence of or an amount of a target analyte, e.g., a target nucleic acid. PATENT Attorney Docket No: EXCT-42343.601 As used herein, the term “flap assay reagents” or “invasive cleavage assay reagents” refers to a collection of all reagents required for performing a flap assay or invasive cleavage assay. As is known in the art, flap assays generally include oligonucleotides for forming an invasive cleavage structure, a flap endonuclease and, optionally, a FRET cassette or 5′ hairpin FRET reporter. Flap assay reagents may optionally contain a target to which the invasive oligonucleotide and flap oligonucleotide bind. As used herein, the term “FRET cassette” refers to a hairpin oligonucleotide that contains a fluorophore moiety and a nearby quencher moiety that quenches the fluorophore. Hybridization of a cleaved flap (e.g., from cleavage of a target-specific probe in a PCR-flap assay assay) with a FRET cassette produces a secondary substrate for the flap endonuclease, e.g., a FEN-1 enzyme. Once this substrate is formed, the 5′ fluorophore-containing base can be cleaved from the cassette by the flap endonuclease, thereby generating a fluorescence signal. In preferred embodiments, a FRET cassette comprises an unpaired 3′ portion to which a cleavage product, e.g., a portion of a cleaved flap oligonucleotide, can hybridize to form an invasive cleavage structure cleavable by a FEN-1 endonuclease. As used herein, the term “PCR-flap assay” is used interchangeably with the term “PCR- invasive cleavage assay” and refers to an assay configuration combining PCR target amplification and detection of the amplified DNA by formation of a first overlap cleavage structure comprising amplified target DNA, and a second overlap cleavage structure comprising a cleaved 5′ flap from the first overlap cleavage structure and a labeled reporter oligonucleotide, e.g., a “FRET cassette” or 5′ hairpin FRET reporter oligonucleotide. In the PCR-flap assay as used herein, the assay reagents comprise a mixture containing DNA polymerase, FEN-1 endonuclease, a primary probe comprising a portion complementary to a target nucleic acid, and a FRET cassette or 5′ hairpin FRET reporter, and the target nucleic acid is amplified by PCR and the amplified nucleic acid is detected simultaneously (i.e., detection occurs during the course of target amplification). PCR-flap assays include the QuARTS assays described in U.S. Pat. Nos. 8,361,720; 8,715,937; and 8,916,344, and the amplification assays of US Pat. No.9,096,893 (for example, as diagrammed in Figure 1 of that patent), each of which is incorporated herein by reference in its entirety. As used herein, the term “PCR-flap assay reagents” refers to one or more reagents for detecting a target nucleic acid in a PCR-flap assay, the reagents comprising nucleic acid PATENT Attorney Docket No: EXCT-42343.601 molecules capable of participating in amplification of a target nucleic acid and in formation of a flap endonuclease substrate in the presence of the target nucleic acid, preferably in a mixture containing DNA polymerase, FEN-1 endonuclease and a FRET cassette or 5′ hairpin FRET reporter. As used herein, the term “FRET” refers to fluorescence resonance energy transfer, a process in which moieties (e.g., fluorophores) transfer energy e.g., among themselves, or, from a fluorophore to a non-fluorophore (e.g., a quencher molecule). In some circumstances, FRET involves an excited donor fluorophore transferring energy to a lower-energy acceptor fluorophore via a short-range (e.g., about 10 nm or less) dipole-dipole interaction. In other circumstances, FRET involves a loss of fluorescence energy from a donor and an increase in fluorescence in an acceptor fluorophore. In still other forms of FRET, energy can be exchanged from an excited donor fluorophore to a non-fluorescing molecule (e.g., a quenching molecule). FRET is known to those of skill in the art and has been described (See, e.g., Stryer et al., 1978, Ann. Rev. Biochem., 47:819; Selvin, 1995, Methods Enzymol., 246:300; Orpana, 2004 Biomol Eng 21, 45-50; Olivier, 2005 Mutant Res 573, 103-110, each of which is incorporated herein by reference in its entirety). As used herein, the term “kit” refers to any delivery system for delivering materials, e.g., materials to be used together for performing a task, from one location to another. In the context of sample collecting and / or processing, such delivery systems include systems that allow for the collection, storage, transport, delivery, and / or for processing samples (e.g., sample stabilizing reagents; sample processing reagents such as particles, buffers, denaturants, oligonucleotides, test tubes, assay plates, filters, assay reaction components, etc. in the appropriate containers) and / or supporting materials (e.g., sample processing or sample storage vessels, written instructions for performing a procedure, etc.). For example, kits generally include one or more enclosures (e.g., boxes) containing the relevant devices and reagents and / or supporting materials. As used herein, the term “fragmented kit” refers to a delivery system comprising two or more separate containers that each contains a subportion of the total kit components. The containers may be delivered to the intended recipient together or separately. For example, a first container may contain materials for sample collection and a buffer, e.g., a preservative solution or a stabilization buffer. A second container may contain reagents for detection of one or more biomarkers. For example, a second container may contain reagents for purifying a target analyte, PATENT Attorney Docket No: EXCT-42343.601 e.g., a chaotropic agent, a silicate material, a binding solution or components for making a binding solution, and inhibitor binding agents. The term “fragmented kit” is intended to encompass kits containing Analyte specific reagents (ASR's) regulated under section 520(e) of the Federal Food, Drug, and Cosmetic Act, but are not limited thereto. Indeed, any delivery system comprising two or more separate containers that each contains a subportion of the total kit components are included in the term “fragmented kit.” For example, a fragmented kit may contain analyte-specific reagents, reagents for nucleic acid extraction, and / or conversion reagents such as bisulfite or other methylation-sensitive conversion reagents. Alternatively, a fragmented kit comprising analyte specific reagents may be used in conjunction with a commercially available kit for nucleic acid extraction. In such embodiments, the kit may comprise reagents for sample collection and a cell stabilization buffer, and may be used in conjunction with a suitable kit for nucleic acid extraction to isolate nucleic acid from the sample prior to detecting one or more biomarkers, such as biomarkers described herein. In contrast, a “combined kit” refers to a delivery system containing all of the components for sample collection, processing, and assaying in a single container (e.g., in a single box housing each of the desired components). The term “kit” includes both fragmented and combined kits. The term “system” as used herein refers to a collection of articles for use for a particular purpose, e.g., a collection of devices, reagents, and instruments for collecting a sample (e.g., in preparation for analyzing the sample), or for collecting, processing and / or analyzing a sample for a particular purpose. In some embodiments, the articles of a system comprise instructions for use, as information supplied on e.g., an article, on paper, on recordable media (e.g., DVD, flash drive, etc.). In some embodiments, instructions direct a user to an online location, e.g., a website for viewing, hearing, and / or downloading instructions. In some embodiments, instructions or other information are provided as an application (“app”) for a mobile device. BRIEF DESCRIPTION OF THE DRAWINGS Fig.1 provides an illustration of an embodiment of the technology wherein a clarified supernatant is provided by collection of a fluid fraction from a dispersed sample. The clarified supernatant is mixed with a silica matrix in the presence of a chaotropic agent and alcohol under conditions that do not favor nucleic acid binding to the silica matrix. The silica matrix is PATENT Attorney Docket No: EXCT-42343.601 removed (e.g., by filtration, as illustrated) to produce a pre-treated clarified supernatant suitable for nucleic acid extraction. The dashed line indicates that the sample may optionally be treated with an inhibitor-adsorbing compound, e.g., PVPP particles, which are also removed (e.g., by filtration, as illustrated) to produce pre-treated clarified supernatant suitable for nucleic acid extraction. The inhibitor adsorption treatment may also be applied to the clarified supernatant before the silica treatment step, or may be combined with the silica treatment in a single step. Figs.2A-2H illustrate additional exemplary embodiments of the technology. FIG.2A illustrates an exemplary embodiment wherein the fluid fraction from stool homogenate is treated with a silica adsorption matrix and a chaotropic agent, followed by removing the silica to produce a pre-cleared sample. FIG.2B illustrates an exemplary embodiment wherein the fluid fraction from stool homogenate is treated with a silica adsorption matrix and a chaotropic agent and heated, followed by removing the silica to produce a pre-cleared sample. FIG.2C illustrates an exemplary embodiment wherein the stool homogenate is contacted with a chaotropic agent, followed by treating the fluid fraction from the homogenate (which fluid fraction contains the chaotropic agent) with a silica adsorption matrix, followed by removing the silica to produce a pre-cleared sample. FIG.2D illustrates an exemplary embodiment wherein the stool homogenate is treated with a silica adsorption matrix and a chaotropic agent and heated, followed by removing the fluid fraction, followed by removing the silica from the fluid fraction to produce a pre-cleared sample. FIG.2E illustrates an exemplary embodiment wherein the stool homogenate is treated with a chaotropic agent, followed by treating the fluid fraction from the homogenate (which fluid fraction contains the chaotropic agent) with a silica adsorption matrix and heating the sample, followed by removing the silica from the fluid fraction to produce a pre-cleared sample. FIG.2F illustrates an exemplary embodiment wherein the stool homogenate is treated with a chaotropic agent and heated, followed by treating the fluid fraction (which fluid fraction contains the chaotropic agent) with PVPP, followed by removing PVPP from the fluid fraction to produce a pre-cleared sample. FIG.2G illustrates an exemplary embodiment wherein the stool homogenate is centrifuged to remove solids, followed by filtering the fluid fraction to remove residual solids from the fluid fraction to produce a pre-cleared sample. FIG.2H illustrates an exemplary embodiment wherein the stool homogenate is centrifuged to remove solids, followed by treating the fluid fraction with PVPP, followed by removing PVPP from the fluid fraction to produce a pre-cleared sample. Although the exemplary embodiments in FIG.2 are illustrated PATENT Attorney Docket No: EXCT-42343.601 using a stool homogenate as the initial sample, any of the above processes may be performed using any suitable fluid sample. Fig.3 illustrates additional exemplary embodiments of the technology. Fig.4 shows tables indicating the Qubit measurement for total DNA and the LQAS measurements for Marker DNAs 1-8 from the Qiagen extraction and the bead-binding extractions for different amounts of input sample, as described in Example 1. Fig.5 shows a table comparing the Qubit measurement for total DNA and the LQAS measurements for Marker DNAs 1-8 from the Qiagen extraction and the bead-binding extractions 0.1 mL of input sample from each pool of pre-treated clarified supernatant, as described in Example 1. Fig.6 shows tables comparing the Qubit measurement of total DNA isolated from 1.0 mL of clarified stool supernatant treated with different combined concentrations of guanidine thiocyanate (“GTC”) and isopropyl alcohol (“IPA”), as described in Example 2. Fig.7 shows tables comparing the LQAS measurements of Marker DNAs 1, 2, and 3, isolated from 1.0 mL of clarified stool supernatant treated with different combined concentrations of GTC and isopropyl alcohol IPA, as described in Example 2. Fig.8 shows tables comparing the LQAS measurements of Marker DNAs 1, 2, and 3, isolated from 1.0 mL of clarified stool supernatant treated with different combined concentrations of GTC and IPA, and diluted 1:10 prior to LQAS measurement, as described in Example 2. Fig.9 shows a table comparing the Qubit measurements for total DNA and the LQAS measurements for Marker DNAs 1-3 from the bead-binding extractions of 1.0 mL of input samples pre-treated with different amounts of silica gel or with 600 µL of paramagnetic particles, as described in Example 3. Fig.10 shows a Oneway analysis of Marker 1 LQAS measurements from DNA extracted by bead binding from input samples pre-treated with different amounts of silica gel or with 600 µL of paramagnetic particles, as described in Example 3. PATENT Attorney Docket No: EXCT-42343.601 Fig.11 shows a Oneway analysis of Marker 2 LQAS measurements from DNA extracted by bead binding from input samples pre-treated with different amounts of silica gel or with 600 µL of paramagnetic particles, as described in Example 3. Fig.12 shows a Oneway analysis of Marker 3 LQAS measurements from DNA extracted by bead binding from input samples pre-treated with different amounts of silica gel or with 600 µL of paramagnetic particles, as described in Example 3. DETAILED DESCRIPTION OF THE INVENTION As described above, embodiments of the present technology provide methods and compositions related to pre-treating complex samples comprising nucleic acids to remove or reduce amounts of substances that may interfere with extraction of nucleic acids from the sample and / or with assaying nucleic acids extracted in the sample. Exemplary, non-limiting methods are described below and as set forth in the Summary of the Invention, which is incorporated here by reference. The technology herein relates to methods of extracting nucleic acids from complex samples, and particularly to methods of reducing interfering compounds that may interfere with extraction of the nucleic acids, and / or co-purify with nucleic acids and interfere with downstream assays. Complex samples such as soil, clay, and stool are known to contain components that may interfere with purification and analysis of analytes in several ways. Such samples comprise components, e.g., phenolic substances, polysaccharides, and humic substances, that can interfere with nucleic acid purification steps, e.g., by binding to nucleic acids in competition with purification matrices (e.g., silica beads, columns, or filters), or that bind to the purification matrices in competition with the nucleic acids. Some interfering compounds co-purify with nucleic acids and inhibit enzymes used to later modify or detect extracted nucleic acids. See, e.g., WO 2006 / 073472, which is incorporated herein by reference. For example, stool samples, e.g., human feces, are rich in biotin, as normal microflora of the large intestine synthesize and release a substantial amount of free biotin. See, e.g., p159, col.2 of HM Said, “Cell and Molecular Aspects of Human Intestinal Biotin Absorption” The Journal of Nutrition.139(1):158-162 PATENT Attorney Docket No: EXCT-42343.601 (2009), and additional biotin may be added from dietary sources. Excess biotin in samples interferes with methods and assays that use the avidin-biotin binding system. See, e.g., “Avidin- Biotin Interaction” ThermoFisher Scientific (world wide web dot thermofisher.com / us / en / home / life-science / protein-biology / protein-biology-learning- center / protein-biology-resource-library / pierce-protein-methods / avidin-biotin-interaction.html). It has been confirmed that biotin in patient samples can be enough to interfere with diagnostic tests that use the avidin-streptavidin binding system. See, e.g., Barbesino, “The Unintended Consequences of Biotin Supplementation: Spurious Immunoassay Results Lead To Misdiagnoses” (world wide web dot aacc.org / publications / cln / articles / 2016 / december / bench- matters-december-2016). One method of separating total nucleic acid from other sample components is to use organic extraction, e.g., phenol-chloroform extraction, to partition and remove interfering components. Unfortunately, this method cannot be easily automated or used in high throughput settings. Additionally, organic extraction requires the use of hazardous chemicals. An alternative approach to total nucleic acid isolation comprises using an adsorption matrix, e.g., a silica matrix, to selectively bind nucleic acids. This is typically done using silica or a silicate surface in the form of membranes or beads, e.g., magnetic beads. However, as discussed above, complex samples may contain large amounts of substances that interfere with nucleic acid binding to silica, as well as substances that copurify with nucleic acids through the silica binding, washing, and elution steps. Thus, silica-based purification, while generally readily automated, may be inefficient or ineffective, depending on the nature and amount of the complex sample being treated. Most of the current commercial soil and stool extraction kits use silica-based matrixes and are limited to low input volumes of fluid collected from the sample (e.g., 100-300µl) to avoid overloading the silica with interfering compounds. The limited input volume means that the quantity of extracted nucleic acid produced is also limited. Further, as discussed above, the quality of the nucleic acid produced can vary greatly, depending, e.g., on the nature of the interfering substances present in the original sample. Low yields of total DNA and the presence of co-purifying assay inhibitors limits sensitivity of downstream detection assays that are used on nucleic acids produced using these PATENT Attorney Docket No: EXCT-42343.601 extraction methods. Further, current methods for processing complex samples that contain high levels of interfering substances, e.g., methods that comprise organic extraction, are hazardous, time consuming, and are incompatible with automation and high-throughput workflow. Thus, an aspect of the present technology provides extraction of total nucleic acid from complex samples in a manner that removes interfering substances, that allows for use of larger sample portions, and that is readily adaptable for automation and high throughput. The technology is not limited to any particular manner of nucleic acid isolation following pre-treatment of fluid samples using the technology described herein. For example, the pre- treated sample may be further processed using methods comprising surfaces with or without affinity reagents attached. For example, nucleic acid from the pre-treated fluid sample may be further purified by adsorption to a nucleic acid binding material, e.g., a silicate surface (including but not limited to beads, column matrices, filters, or other structures) in the presence of reagents that favor nucleic acid binding to the binding material, e.g., chaotropic agents alone or in the presence of alcohol, preferably at concentrations higher than used during the pre-treating step of the present technology. See, e.g., U.S. Pat. Nos.5,234,809; 9,809,612; 9,790,250; 10,738,069, and WO 2009 / 146775, each of which is incorporated herein by reference in its entirety, for all purposes. Nucleic acids from the pre-treated fluid sample may also be isolated by affinity capture, e.g., using a nucleic acid binding protein (e.g., an anti-ds or ssDNA antibody, an antibody specific for methylated DNA, or a methylation binding protein or a methylation binding domain of a protein), or using a sequence-specific reagent, such as a complementary capture oligonucleotide. In some embodiments such affinity reagents are bound to nucleic acid in the pre-treated fluid sample and the affinity reagent-nucleic acid complex is then bound to a surface, e.g., a bead, for separation from the pre-treated fluid sample. In other embodiments, an affinity reagent is attached to a surface, such as a bead (e.g., covalently or non-covalently) and the bead- affinity reagent is then used to capture nucleic acid from the pre-treated fluid sample. Figs.1-3 provide schematic diagrams illustrating embodiments of the technology. As illustrated in Fig.1, a fluid sample, e.g., a fluid fraction collected from a complex sample is treated with an adsorption matrix, e.g., a silica adsorption matrix, to remove interfering compounds. In some embodiments, the technology presented herein provides a means of PATENT Attorney Docket No: EXCT-42343.601 substantially reducing interfering substances present in large-volume complex samples such that larger input volumes of the pre-treated sample may be processed using common and convenient extraction systems, e.g., silica filters (columns) or bead systems that are amenable to high throughput processing and automated processing. Another aspect of the technology is to provide a pre-treatment system that may be applied to many different kinds of samples that may contain nucleic acid, e.g., soil, sewage, feces, etc., such that the same or similar pre-treatment and follow-on nucleic acid extraction methods may be applied to different sample types, regardless of the input sample source. For example, in some embodiments, the technology is applied to suspensions of soil or other environmental samples, stool homogenates, urine, cell lysates, tissue homogenates, blood or blood products, cell cultures, fermented products, etc., and in some embodiments, the technology is applied to clarified supernatants produced from suspensions of soil or other environmental samples, stool homogenates, urine, cell lysates, tissue homogenates, blood or blood products, cell cultures, fermented products, etc. In some embodiments the samples are simply homogenized in a buffer to form a fluid sample, in some embodiments, a fluid fraction is collected, and in some embodiments, the samples are exposed to a lysis treatment before treatment of a fluid sample, or before a fluid fraction is separated. The samples may be, e.g., homogenized in a dispersing fluid alone, or in the presence of bead cell disruptors (“bead beating”), detergents, proteases, chaotropic agents, or other agents that disassociate nucleic acid from other sample components. During development of the technology, some interfering substances from samples were found to directly compete with DNA for binding to silica matrix used in the ultimate purification process. At conditions optimal for DNA sorption to silica, these interfering components preferentially bind to the beads (or membrane) of, for example, spin columns, reducing DNA binding. Reduction in the nucleic acid binding capacity of purification columns makes the extraction process highly inefficient and limits the amount of sample that can be processed per column or per amount of silica reagent. During development of the technology, it was determined that the effect of the interfering compounds could be reduced or eliminated if the fluid sample (e.g., clarified supernatant, sample homogenate, e.g., stool homogenate, etc.) is first incubated with a matrix capable of binding the interfering impurities but using conditions selected to minimize or eliminate nucleic acid binding PATENT Attorney Docket No: EXCT-42343.601 to the matrix. In one embodiment, a fluid sample is incubated with a silica gel (e.g., silica gel chromatography medium) or magnetic silica beads under conditions wherein interfering substances are bound to the silica gel or magnetic silica beads, but wherein nucleic acids in the fluid sample are not bound in any significant amount to the silica gel or magnetic silica beads. In another embodiment, a fluid sample is incubated with a silica gel or magnetic silica beads under conditions wherein interfering substances are bound, preferably strongly bound, to the silica gel or magnetic silica beads, but wherein only fraction of nucleic acids in the fluid sample are bound to the silica gel chromatography medium or magnetic silica beads, e.g., wherein less than about 75%, preferably <50%, preferably < 25%, preferably < 20%, preferably 15%, preferably <10%, preferably < 5%, more preferably <1% of the nucleic acids in the clarified supernatant are bound. In some embodiments, the binding solution used in the pre-treating step consists of the same components generally present in nucleic acid binding to silica surfaces, however concentrations of these components are altered (e.g., reduced or increased in concentration, or a weaker chaotrope is used in place of a stronger chaotrope), to minimize nucleic acid binding to silica during the pre-treatment step. During development of the technology, it was observed that, because many interfering compounds have higher affinity to silica than do nucleic acids, binding conditions that are considered suboptimal or poor for nucleic acid binding to silica are nonetheless suitable for binding interfering compounds in a fluid sample to silica during a pre- treatment step. After treatment of the fluid sample, e.g., a clarified supernatant, with the pre- sorption silica matrix, the matrix bound with interfering compounds is removed, e.g., by filtration, centrifugation, or magnetic separation. The pre-treated fluid sample depleted of interfering compounds may then be processed to extract nucleic acids. For example, the pre- treated fluid sample may be used as input for extraction columns, extraction beads, and is particularly suitable for use automated nucleic acid extraction methods. This silica pre-treatment process may be used alone or may be combined with other assay inhibitor removal methods, e.g., the use of polyvinylpolypyrrolidone particles (or other assay inhibitor adsorbents), with the PVPP being used before or after the silica pre-treatment, or combined with the silica pre-treatment in a single step. In some embodiments, soluble polyvinylpyrrolidone is used in a reagent buffer used to treat the analyte during the extraction procedure. PATENT Attorney Docket No: EXCT-42343.601 In some embodiments, the fluid sample is heated. For example, in some embodiments, a silica pre-treatment process is conducted at an elevated temperature (e.g., a temperature exceeding room temperature). In some embodiments, the silica pre-treatment process is conducted at a temperature of 30°C to 100°C. For example, in some embodiments the methods herein comprise combining the fluid sample with the silica adsorption matrix in a solution comprising the chaotropic agent, thereby forming the mixture, and incubating mixture for a period of 1 minute to 6 hours at a temperature of 30°C to 100°C prior to removing or separating the silica adsorption matrix from the mixture to produce the pre-treated fluid sample comprising nucleic acids. In some embodiments, the first reaction mixture is cooled to room temperature prior to removing or separating the silica adsorption matrix. In some embodiments, the mixture is incubated for a period of 1 minute to 6 hours, 2 minutes to 5 hours, 3 minutes to 4 hours, 4 minutes to 3 hours, or 5 minutes to 2 hours. In some embodiments, the mixture is incubated for a period of 1 minute to 1 hour, 2 minutes to 45 minutes, 3 minutes to 30 minutes, 4 minutes to 20 minutes, or 5 minutes to 10 minutes. In some embodiments, the mixture is incubated for a period of at least 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, or 115 minutes up to no more than 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, or 120 minutes. In some embodiments, the mixture is incubated at a temperature of at least 30°C, at least 35°C, at least 40°C, at least 45°C, at least 50°C, at least 55°C, at least 60°C, at least 65°C, at least 70°C, at least 75°C, at least 80°C, at least 85°C, at least 90°C, or at least 95°C up to no more than 35°C, no more than 40°C, no more than 45°C, no more than 50°C, no more than 55°C, no more than 60°C, no more than 65°C, no more than 70°C, no more than 75°C, no more than 80°C, no more than 85°C, no more than 90°C, or no more than 95°C, or no more than 100°C. A further aspect of this technology is a reagents kit for the extraction of nucleic acids contained in samples, comprising: (a) a solution suitable for taking up a sample to form a homogenate or dispersed fluid sample, and (b) a silica matrix for binding interfering compounds in a homogenate or in a fluid fraction from the homogenate to produce a pre-treated fluid sample; and, optionally (c) reagents and / or devices for extracting nucleic acid from a pre-treated fluid sample. PATENT Attorney Docket No: EXCT-42343.601 In some embodiments, the reagents kit comprises instructions for extracting nucleic acids. In some embodiments, the instructions comprise any one of the methods disclosed herein. An example of a dispersing fluid that is suitable to homogenize or disperse a sample containing nucleic acids is a buffer system based on Tris-HCl, with EDTA and optionally NaCl. Another example of a dispersing fluid suitable to homogenize a sample is a buffer system comprising a buffering agent, a detergent, a salt, at least one preservative selected from sodium azide and gentamicin, and at a chelating agent, preferably EDTA. In some embodiments, a dispersing fluid comprises a protoporphyrin IX complex. Silica adsorbant matrices In some aspects, the technology provided herein relates to treatment of relatively crude samples to adsorb and remove interfering substances from liquid fractions from the samples. The method is not limited to particular silicate surfaces, compositions having high surface area e.g., particles or beads, and that can be mixed or agitated to increase exposure of the fluid to binding surfaces, are preferred. Beads and particles may be magnetic (e.g., for separation by use of a magnet) or may be non-magnetic (e.g., for separation by centrifugation or filtration). In some embodiments, magnetic beads are used for the treatment, e.g., beads comprising a magnetic core and a silica coating. The silica coating binds the interfering substances, and the magnetic core provides an efficient way to concentrate and remove the beads with the interfering substances using a magnet. In some embodiments, the silica-coated magnetic beads are MagneSil Paramagnetic Particles (Promega, Madison, WI; catalogue number AS1220 or AS640A, promega.com). The technology is not limited to any particular type of magnetic bead. Embodiments of the technology described herein make use of any magnetic beads (e.g., paramagnetic beads) that have an affinity for undesirable substances under binding conditions. In some embodiments, the magnetic beads have a magnetite (e.g., Fe3O4) core and a coating comprising silicon dioxide (SiO2). The bead structure (e.g., size, porosity, shape) and composition of the binding solution used during the pre-treating step can be altered to bind different types of inhibitors. In some embodiments, the particles may bind nucleic acids (e.g., DNA or RNA in single stranded, double stranded, or other forms or conformations; nucleic acids derived from a natural source, synthesized chemically, synthesized enzymatically (e.g., by PCR)) and sizes of nucleic PATENT Attorney Docket No: EXCT-42343.601 acids (e.g., small oligomers, primers, genomic, plasmids, fragments, e.g., consisting of 200 or fewer bases) under some conditions, but they do not bind the nucleic acids under the conditions used to selectively bind interfering compounds. Related technologies are described, e.g., in U.S. Pat. Nos.6,194,562; 6,270,970; 6,284,470; 6,368,800; 6,376,194, each incorporated herein by reference. Also contemplated are magnetic beads coated with, e.g., organosilane (as described in U.S. Pat. No.4,554,088); carboxylated polyacrylate (as described in U.S. Pat. No.5,648,124); cellulose (as described in U.S. Pat. Appl. Ser. No.10 / 955,974); hydroxysilane (as described in U.S. Pat. Appl. Ser. No.11 / 459,541); and hydrophobic aliphatic ligands (as described in U.S. Pat. Appl. Ser. No.12 / 221,750), each incorporated herein by reference for all purposes. The technology is not limited to a particular size of bead or particle. Accordingly, embodiments of the technology use magnetic beads of a number of different sizes. Smaller beads provide more surface area (per weight unit basis) for adsorption, but if magnetic beads are used, smaller beads are limited in the amount of magnetic material that can be incorporated in the bead core relative to a larger bead. In some embodiments, the particles are distributed over a range of sizes with a defined average or median size appropriate for the technology for which the beads are used. In some embodiments, the particles are of a relatively narrow monomodal particle size distribution. In some embodiments, the beads that find use in the present technology have pores that are accessible from the exterior of the particle. Such pores have a controlled size range that is sufficiently large to admit an interfering macromolecule, e.g., a polyphenol or carbohydrate, into the interior of the particle and to bind to the interior surface of the pores. The pores are designed to provide a large surface area that is capable of binding a material to be bound. When paramagnetic beads are used, beads (and bound material) are removed from a mixture using a magnetic field. In some embodiments, other forms of external force in addition to a magnetic field are used to isolate the biological target substance according to the present technology. For example, suitable additional forms of external force include, but are not limited to, gravity filtration, vacuum filtration, and centrifugation. Embodiments of the technology apply an external magnetic field to remove the beads from the medium. Such a magnetic field can be suitably generated in the medium using any one of a number of different known means. For example, one can position a magnet on the outer surface of a container of a solution containing the beads, causing the particles to migrate through PATENT Attorney Docket No: EXCT-42343.601 the solution and collect on the inner surface of the container adjacent to the magnet. The magnet can then be held in position on the outer surface of the container such that the particles are held in the container by the magnetic field generated by the magnet, while the solution is decanted out of the container and discarded. A second solution can then be added to the container, and the magnet removed so that the particles migrate into the second solution. Alternatively, a magnetizable probe could be inserted into the solution and the probe magnetized, such that the particles deposit on the end of the probe immersed in the solution. The probe could then be removed from the solution, while remaining magnetized. Commercial sources exist for magnets designed to be used in both types of magnetic removal and transfer techniques described in general terms above. See, e.g., MagneSphere Technology Magnetic Separation Stand or the PolyATract Series 9600TM Multi-Magnet, both available from Promega Corporation; Magnetight Separation Stand (Novagen, Madison, Wis.); or Dynal Magnetic Particle Concentrator (Dynal, Oslo, Norway). Some embodiments comprise use of a magnetic device according to U.S. Pat. Appl. Ser. No.13 / 089116, which is incorporated herein by reference in its entirety for all purposes. Furthermore, some embodiments contemplate the use of a “jet channel” or pipet tip magnet separation (e.g., as described in U.S. Pat. Nos.5,647,994 and 5,702,950). Some embodiments contemplate the use of an immersed probe approach (e.g., as described in U.S. Pat. Nos.6,447,729 and 6,448,092), e.g., as exemplified by the KingFisher systems commercially available from Thermo Scientific. In some embodiments, the nucleic acids in the pre-treated clarified supernatant are extracted from the fluid using the same or similar type of particles or beads, with the binding conditions adjusted to favor nucleic acid binding. For example, in some embodiments, the pre- treated fluid fraction from the sample is combined with additional amounts of the same or a different chaotropic agent and / or additional alcohol, e.g., isopropanol, to increase nucleic acid binding. Dispersed Samples In some embodiments, the silica pre-treatment is applied to at least a portion of a fluid fraction from a dispersed sample. In some embodiments, the dispersed sample is produced by dispersing sample material that is at least partially solid or semisolid in a dispersing fluid. In some embodiments, the sample material is stool. In some embodiments, the dispersed sample is PATENT Attorney Docket No: EXCT-42343.601 then partitioned into a solids fraction and a fluid fraction. In some embodiments, a fluid fraction or a portion thereof is then treated with the adsorption matrix (e.g. silica adsorption matrix) in a binding solution comprising a chaotropic agent to remove interfering compounds. In some embodiments, the dispersed sample is treated with the adsorption matrix, e.g., prior to removal of a fluid fraction or portion. A dispersed sample is not limited to any particular ratio of dispersing fluid to sample in preparing a fluid sample. For example, in some embodiments, a volume of dispersing fluid is combined with a volume or weight of sample material in a 1:1 ratio, while in some embodiments, the proportion of dispersing fluid may be used at a ratio of 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, 200:1, 300:1, 400:1, 500:1, or 1000:1, including any fractional amount therebetween, relative to a single portion of sample (v:v or v:w). In some embodiments, a ratio of dispersing fluid:sample is greater than 1000:1. In some embodiments, the dispersing fluid comprises one or more of a chaotropic agent, an alcohol, a detergent, a salt, a preservative, a buffering agent, a protein, a protoporphyrin IX complex, a nuclease inhibitor, and a nuclease. In some embodiments, the dispersing fluid comprises two or more of a chaotropic agent, an alcohol, a detergent, a salt, a preservative, a buffering agent, a protein, a protoporphyrin IX complex, a nuclease inhibitor, and a nuclease. In some embodiments, the dispersing fluid comprises three or more of a chaotropic agent, an alcohol, a detergent, a salt, a preservative, a buffering agent, a protein, a protoporphyrin IX complex, a nuclease inhibitor, and a nuclease. In some embodiments, the dispersing fluid comprises four or more of a chaotropic agent, an alcohol, a detergent, a salt, a preservative, a buffering agent, a protein, a protoporphyrin IX complex, a nuclease inhibitor, and a nuclease. In some embodiments, the dispersing fluid comprises five or more of a chaotropic agent, an alcohol, a detergent, a salt, a preservative, a buffering agent, a protein, a protoporphyrin IX complex, a nuclease inhibitor, and a nuclease. In some embodiments, the dispersing fluid comprises six or more of a chaotropic agent, an alcohol, a detergent, a salt, a preservative, a buffering agent, a protein, a protoporphyrin IX complex, a nuclease inhibitor, and a nuclease. In some embodiments, the dispersing fluid comprises three or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. In some PATENT Attorney Docket No: EXCT-42343.601 embodiments, the dispersing fluid comprises four or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. In some embodiments, the dispersing fluid comprises five or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. In some embodiments, the dispersing fluid comprises a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex. In some embodiments, the dispersing fluid is optimized for recovery of nucleic acids from the dispersed sample. In some embodiments, the dispersing fluid is optimized for recovery of RNA from the dispersed sample. In some embodiments, the dispersing fluid is optimized for recovery of DNA from the dispersed sample. In some embodiments, the dispersing fluid comprises a chaotropic agent. In some embodiments, the chaotropic agent is selected from guanidine thiocyanate, guanidine isothiocyanate, and guanidine HCl. In some embodiments, the dispersing fluid comprises 0% to 20% of a chaotropic agent (w / v). For example, in some embodiments the dispersing fluid comprises 0% to 20%, 0% to 15%, 0% to 10%, 0.01% to 9%, 0.02% to 8%, 0.03% to 7%, 0.04% to 6%, 0.05% to 5%, 0.06% to 4%, 0.07% to 3%, 0.8% to 2%, or 0.09% to 1%, or 0.1% to 0.5% chaotropic agent. In some embodiments, the dispersing fluid comprises an alcohol. In some embodiments, the alcohol is selected from short-chain branched or unbranched alkanols having from 1 to 5 carbon atoms. Exemplary alcohols include, but are not limited to, methanol, ethanol, propanol, isopropanol, butanols or pentanols, or mixtures thereof. In some embodiments, the dispersing fluid comprises 0% to 30% alcohol (v / v). For example, in some embodiments the dispersing fluid comprises 0% to 30% alcohol, 0% to 20% alcohol, 0% to 15% alcohol, 0% to 10%, 0.01% to 9%, 0.02% to 8%, 0.03% to 7%, 0.04% to 6%, 0.05% to 5%, 0.06% to 4%, 0.07% to 3%, 0.8% to 2%, or 0.09% to 1%, or 0.1% to 0.5% alcohol. In some embodiments, the dispersing fluid comprises a detergent. In some embodiments, the detergent comprises an anionic detergent (e.g. sodium dodecyl sulfate; sodium lauryl sulfate; ammonium lauryl sulfate), a cationic detergent (e.g. quaternary ammonium compounds, benzalkonium chloride (BAC), cetyltrimethylammonium bromide, linear alkylbenzene sulfonates, sodium dodecylbenzene sulfonate, tetradecyltrimethylammonium oxalate, cetyltrimethylammonium bromide (CTAB), tetradecyltrimethylammonium bromide (TTAB), PATENT Attorney Docket No: EXCT-42343.601 dodecyltrimethylammonium bromide (DTAB), hexadecyltrimethylammonium chloride (CTAC)), a non-ionic detergent (e.g. IPEGAL CA-630 (octylphenoxy poly(ethyleneoxy)ethanol), TWEEN detergents such as polyoxyethylene (20) sorbitan - monolaurate; -monopalmitate; -monostearate; or -monooleate; TRITON detergents such as polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether, steroid and steroidal glycosides such as saponin or digitonin), a zwitterionic detergent (i.e. amphoteric) detergent (e.g.3-[(3- cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)), or a mixture of detergent agents, e.g. TEEPOL® detergent comprising sodium dodecylbenzene sulfonate and sodium C12- C15 alcohol ether sulfate. In some embodiments, the dispersing fluid comprises 0% to 10% detergent (v / v). For example, in some embodiments the dispersing fluid comprises 0% to 10%, 0.01% to 9%, 0.02% to 8%, 0.03% to 7%, 0.04% to 6%, 0.05% to 5%, 0.06% to 4%, 0.07% to 3%, 0.8% to 2%, or 0.09% to 1%, or 0.1% to 0.5% detergent. In some embodiments, the dispersing fluid comprises a salt. In some embodiments, the salt comprises a sodium salt, a potassium salt, or an ammonium salt. In some embodiments, the salt is selected from sodium acetate, sodium citrate, sodium sulfate, sodium chloride, ammonium chloride, ammonium acetate, ammonium sulfate, potassium chloride, and potassium dihydrogen phosphate. In some embodiments, the dispersing fluid comprises 0 mM to 500 mM salt. For example, in some embodiments the dispersing fluid comprises 1 mM to 500 mM, 10 mM to 400 mM, 20 mM to 350 mM, 30 mM to 300 mM, 40 mM to 275 mM, 50 mM to 250 mM, 60 mM to 225 mM, 70 mM to 200 mM, 80 mM to 175 mM, or 90 mM to 150 mM salt. In some embodiments, the dispersing fluid comprises a preservative. In some embodiments, the preservative comprises one or more of sodium azide, disulfonic acid or a salt thereof (e.g.1,2-ethanedisulfonic acid), and an antibiotic (e.g. gentamicin, ampicillin). In some embodiments, the dispersing fluid comprises two or more of sodium azide, disulfonic acid, and gentamicin. In some embodiments, the dispersing fluid comprises three or more of sodium azide, disulfonic acid, and gentamicin. In some embodiments, the dispersing fluid comprises disulfonic acid. For example, in some embodiments the dispersing fluid comprises 1,2-ethanedisulfonic acid. In some embodiments, the dispersing fluid does not comprise disulfonic acid. In some embodiments, the dispersing fluid comprises 0 mol / L to 0.3 mol / L disulfonic acid. In some embodiments, the dispersing fluid comprises .001 mol / L to 0.3 mol / L disulfonic acid (e.g.1,2- PATENT Attorney Docket No: EXCT-42343.601 ethanedisulfonic acid). In some embodiments, the dispersing fluid comprises 0% to 5% sodium azide (w / v). For example, in some embodiments the dispersing fluid comprises 0% to 5%, 0.01% to 2.5%, 0.02% to 2%, or 0.03% to 1.5%, or 0.04% to 1%, or 0.05% to 0.5% sodium azide. In some embodiments, the dispersing fluid comprises 0 µg / ml to 50 µg / ml gentamicin. In some embodiments, the dispersing fluid comprises 0 µg / ml to 50 µg / ml, 5 µg / ml to 40 µg / ml, 10 µg / ml to 30 µg / ml, or 15 µg / ml to 25 µg / ml gentamicin. In some embodiments, the dispersing fluid comprises one or more chelating agents, e.g., ethylenediaminetetraacetic acid (EDTA). In some embodiments, the dispersing fluid comprises 0 mM to 100 mM EDTA. In some embodiments, the dispersing fluid comprises 0 mM to 100 mM, 0 mM to 75 mM, 1 mM to 50 mM, 2 mM to 40 mM, 3 mM to 30 mM, 4 mM to 20 mM, or 5 mM to 15 mM EDTA. In some embodiments, the dispersing fluid comprises a buffering agent. In some embodiments, the buffering agent comprises HEPES (4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid), PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid), MES (2-(N- morpholino)ethanesulfonic acid), MOPS (N-morpholino)propanesulfonic acid), a phosphate buffer (e.g. phosphate buffered saline), or TRIS (Tris(hydroxymethyl)aminomethane). In some embodiments, the dispersing fluid comprises 1 mM to 1M buffering agent. For example, in some embodiments the dispersing fluid comprises 1 mM to 1 M, 100 mM to 900 mM, 200 mM to 800 mM, 300 mM to 700 mM, or 400 mM to 600 mM buffering agent. In some embodiments, the dispersing fluid comprises 1 mM to 1 M, 2.5 mM to 500 mM, 5 mM to 250 mM, 10 mM to 100 mM, 15 mM to 50mM, or 20 mM to 30mM buffering agent. In some embodiments, the dispersing fluid comprises a protein. In some embodiments, the protein comprises albumin (e.g. bovine serum albumin). In some embodiments, the dispersing fluid comprises casein. In some embodiments, the dispersing fluid does not comprise a protein. In some embodiments, the dispersing fluid comprises 0% to 30% protein (w / v). In some embodiments, the dispersing fluid comprises 0% to 30% protein, 0% to 20% protein, or 1% to 15% protein. In some embodiments, the dispersing fluid comprises a protoporphyrin, e.g., a protoporphyrin IX complex. In some embodiments, the protoporphyrin comprises iron, zinc, PATENT Attorney Docket No: EXCT-42343.601 chromium, or cobalt. In some embodiments, the dispersing fluid comprises 0.5 µM to 10 µM of the protoporphyrin, e.g., protoporphyrin IX complex. In some embodiments, the dispersing fluid comprises a nuclease inhibitor. In some embodiments, the nuclease inhibitor is a ribonuclease inhibitor. In some embodiments, the dispersing fluid comprises 0% to 10% nuclease inhibitor. In some embodiments, the dispersing fluid comprises a nuclease. In some embodiments, the dispersing fluid comprises 0% to 10% nuclease. In some embodiments, the pH of the dispersing fluid is 5 to 10. In some embodiments, the pH of the dispersing fluid is 5 to 10, 5.5 to 9, 6 to 8, or 6.5 to 7. In some embodiments, the pH of the dispersing fluid is about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about 9.5, or about 10. Removal of assay inhibitors In some embodiments, the pre-treated fluid sample is further treated with a second inhibitor adsorbent, e.g., polyvinylpyrrolidone (PVP), preferably insoluble polyvinylpolypyrrolidone (PVPP) particles. In preferred embodiments, the PVPP particles are removed, e.g., by centrifugation or filtration, e.g., as set forth in WO 2012 / 155072 (Bruinsma), which is incorporated herein by reference for all purposes. As discussed above, the second inhibitor adsorbent may be used before or after the silica matrix pre-treatment step, or may be used at the same time, in a single-step procedure. Alternatively, in some embodiments, a sample may be treated with an inhibitor adsorbent such as, for example, PVP or PVPP, without silica pre-treatment to help recover a particular analyte and / or improve analyte yield. Quantitation of nucleic acid strands In the examples described herein, nucleic acid yield was measured using flap endonuclease assays. Flap Endonuclease assays The QuARTS and LQAS / TELQAS flap assay technologies combine a polymerase-based target amplification process with an invasive cleavage-based signal amplification process. The PATENT Attorney Docket No: EXCT-42343.601 QuARTS technology is described, e.g., in U.S. Pat. Nos.8,361,720; 8,715,937; 8,916,344; and 9,212,392, a flap assay using probe oligonucleotides having a longer target-specific region (Long probe Quantitative Amplified Signal, “LQAS”) and additional embodiments are described in U.S. Pat.10,648,025, and WO 2021 / 041726, each of which is incorporated herein by reference in its entirety for all purposes. The present technology is not limited to use of flap endonuclease assays for detection, and in different embodiments, any method of analyzing the nucleic acids may be used. For example, in some embodiments, the analysis comprises PCR, direct sequencing, pyrosequencing, methylation-sensitive single-strand conformation analysis (MS-SSCA), high resolution melting analysis, methylation-sensitive single-nucleotide primer extension (MS-SnuPE), base-specific cleavage / mass spectrometry (e.g., by MALDI-TOF), PCR, microarray analysis, restriction digest analysis), INVADER assay, combined bisulfite restriction analysis, or methylated DNA immunoprecipitation (MeDIP), and other method described hereinabove. In some embodiments, DNA target strands are analyzed to examine methylation. Exemplary methods of analyzing methylation in DNA strands are provided in WO 2021 / 041726, which is incorporated herein by reference in its entirety for all purposes. In some embodiments, fluid samples are assayed for amounts of proteins, including but not limited to amounts of hemoglobin. In preferred embodiments, assaying fluid samples for proteins comprises immunochemical assaying. In some embodiments, assaying a fluid sample for proteins comprises assaying amounts of proteins such as calprotectin, complement component 3a (C3a), Fc fragment of IgG binding protein (FCGBP), resistin like beta (RETNLB / RELM), S100 calcium binding protein A12 (S100A12), serpin peptidase inhibitor, clade F member 2 (SERPINF2), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A9 (S100A9), complement component 3 (C3), ceruloplasmin (ferroxidase) (CP), transferrin (TF), catalase (CAT), complement component 9 (C9), lactotransferrin (LTF), hemoglobin, beta (HBB), hemopexin (HPX), hemoglobin, alpha 1(HBAl), haptoglobin (HP), glucose-6-phosphate isomerase (GPI), myeloperoxidase (MPO), hemoglobin, delta (HBD), alpha-2-macroglobulin (A2M), cytidine deaminase (CDA), fibrinogen gamma chain (FGG), azurocidin 1 (AZU1), vitronectin (VTN), retinol binding protein 4 (RBP4), KNG1, proteasome (PSMA5), complement component 5 (C5), fibronectin 1 (FN1), lactate dehydrogenase A (LDHA), proteinase 3 (PRTN3) and glutathione reductase (GSR). See, e.g., PATENT Attorney Docket No: EXCT-42343.601 WO 2018 / 217087 to Bosch, and WO 2021 / 076969 to Fourrier, each of which is incorporated by reference in its entirety for all purposes. In some embodiments, a single sample, e.g., a dispersed sample or other fluid sample is tested for one or more proteins, one or more RNA molecules and one or more DNA molecules. EXPERIMENTAL EXAMPLES EXAMPLE 1 Effect of untreated clarified supernatant sample size on nucleic acid yield and on detection assay signal Nucleic acids were captured directly from different volumes of clarified stool supernatant without silica gel pre-treatment to assess the effect of input sample volume on the total yield of DNA from a standard silica-DNA binding procedure and from a commercial kit procedure. The effect of the amount of input sample on the amounts of specific gene targets detectable in the extracted DNA was also examined. Samples used in the following included a pool comprising 12 stool homogenates from human subjects that were negative for colorectal cancer-associated marker DNAs, and a pool comprising 12 stool homogenates from human subjects that were positive for colorectal cancer- associated marker DNAs. To produce the homogenates, stool samples were homogenized in a buffer comprising 500 mM Tris HCl pH 9.0, 150 mM EDTA, and 10 mM NaCl, at approximately 4 mLs of buffer per gram of stool. Homogenates were centrifuged for 45 min. at 4500g to separate suspended solids from a fluid fraction and 20 mL of each supernatant was decanted to a fresh tube comprising PVPP particles in tablet form. After incubation with shaking at room temp. for 15 min, the PVPP particles were removed by filtration to produce clarified stool supernatants. It was determined that treatment of the supernatant with PVPP to remove assay inhibitors did not increase total nucleic acid extraction yield (data not shown). Nucleic acids were extracted from 0.1mL, 0.2mL, 0.5mL, 1.0mL, 2.0mL, and 3.0mL aliquots of the clarified stool supernatants. Each aliquot was combined with 200 µL binding beads (16 mg / mL paramagnetic silica beads) and brought to a total volume of 19.8 mL with a PATENT Attorney Docket No: EXCT-42343.601 binding buffer resulting in final concentrations of 2.03M guanidine thiocyanate and 13.9% isopropyl alcohol. The mixtures were incubated at room temperature for 1 hour with shaking at 400 rpm. The tubes were placed on a magnet to separate the beads and the supernatant fluid was discarded. The beads were resuspended in 900 µL of a binding buffer (3.09M guanidine thiocyanate and 21.21% isopropanol), incubated with shaking for 2 min., then separated from the buffer. After separation, the beads were washed 4 times with a buffer comprising 20 mM Tris-HCl, 0.0125% sodium azide, and 75% isopropanol. After separation from the final wash, the beads were dried for 20 min. at 55°C and the nucleic acid was eluted with 100 µL of 10 mM Tris-HCl pH 8.0, 0.1 mM EDTA. In parallel, 0.1 mL of each clarified supernatant was extracted using a QIAamp® Fast DNA Stool Mini Kit in accordance with the manufacturer’s instructions and eluted in 100 µL of 10 mM Tris-HCl pH 8.0, 0.1 mM EDTA. The resulting samples were analyzed for DNA concentration using Qubit fluorometric quantification (ThermoFisher Scientific). Amounts of specific target DNAs were assayed using the LQAS assay (Exact Sciences) as described in WO 2021 / 041726, which is incorporated herein by reference in its entirety, for all purposes. The results are shown in Fig.4 and 5. The Qubit analysis showed that the method using magnetic silica beads described above produced more total DNA that the Qiagen kit applied to the same volume of input sample (100µL), and that doubling the input sample to 200 µL of clarified supernatant approximately doubled the yield of total DNA from the magnetic silica beads method. Further, the LQAS assays showed a proportional increase in signal from the doubled input sample, suggesting that use of up to 200 µL of clarified supernatant in this procedure did not saturate the magnetic silica beads with interfering substances. Further, as shown in Fig.5, for purifications from 0.1 mL of stool supernatant, the use of the magnetic silica bead method for the final extraction of the DNA, as described above, produced both a higher yield of total DNA and produced stronger signals in the downstream LQAS assays. However, when the sample amounts were further increased to use 0.5mL, 1.0mL, 2.0mL, and 3.0mL aliquots of the clarified stool supernatants, both the total DNA yield and the specific target signals were reduced, indicating that the larger samples volumes carried quantities of PATENT Attorney Docket No: EXCT-42343.601 substances sufficient to interfere with both the total DNA capture and with the downstream LQAS assay reactions. EXAMPLE 2 Effect of pre-treating clarified fluid fraction with silica PVPP-treated clarified fluid fractions as described in Example 1 were used to assess the effect of treating the fluid fraction with silica gel prior to the magnetic silica bead-binding extractions described above. For each pre-treating test, 1 mL of clarified supernatant was combined with 100 mg of silica gel (non-magnetic) in a total volume of 7.2 mL of one of the binding buffers, resulting in final concentrations of 0.5M, 1.0M, 1.5M, or 2.03M guanidine thiocyanate, with 5%, 10%, or 13.9% isopropanol. The samples were incubated at room temperature with shaking at 400 rpm for 1 hour. The silica gel was removed by centrifugation for 6 min. at 3,300xg and the pre-treated supernatants were removed to fresh tubes. To determine whether nucleic acid was lost to the silica gel binding at this step, the removed silica gel was washed 4X with wash buffer comprising 20 mM Tris, 0.0125% sodium azide, and 75% isopropanol, dried, and eluted with 100 µL 10 mM Tris HCl pH 8.0, 0.1 mM EDTA. Nucleic acids were extracted from 1.0 mL aliquots of the silica gel pre-treated stool supernatants mixed with 6.0 mL of 3.09M guanidine thiocyanate and 21.21% isopropanol. Each 7 mL mixture was then combined with 300 µL magnetic binding beads (16 mg / mL paramagnetic silica beads) and brought to a total volume of 19.8 mL with a binding buffer, resulting in final concentrations of 2.03M guanidine thiocyanate and 13.9% isopropyl alcohol. Aliquots of untreated clarified supernatant were included as controls. The mixtures were incubated at room temperature for 1 hour with shaking at 400 rpm. The tubes were placed on a magnet to separate the beads and the supernatant fluid was discarded. The beads were resuspended in 900 µL of a binding buffer (2.83M guanidine thiocyanate and 27.9% isopropanol) and incubated with shaking for 2 min. The beads were collected, then washed 4 times with a wash buffer comprising 20 mM Tris, 0.0125% sodium azide, and 75% isopropanol, then dried for 20 min. at 55°C. The nucleic acid was eluted with 100 µL of 10 mM Tris-HCl pH 8.0, 0.1 mM EDTA. PATENT Attorney Docket No: EXCT-42343.601 The resulting samples were analyzed for total DNA concentration using Qubit fluorometric quantification (ThermoFisher Scientific). Amounts of the same specific target DNAs were assayed using the LQAS assay (Exact Sciences) as described in Example 1. The results shown in Figs.6-9. Fig.6 shows the total amounts of DNA measured for each binding condition in the pre- treatment step, and for DNA eluted from the pre-treating silica gel. Fig.7 shows the amounts of Marker DNAs 1-3 measured for each binding condition in the pre-treatment step, and for DNA eluted from the pre-treating silica gel. Fig.8 shows the effect of a 1:10 dilution of the extracted DNA prior to the LQAS assay measurement, and shows amounts of Marker DNAs 1-3 measured for each binding condition in the pre-treatment step, and for DNA eluted from the pre-treating silica gel. These data show that the combination of 1.0M GTC with 13.9% isopropanol in the pre- treating step resulted in the highest number of detected DNA strands, and that essentially no strands were detected in the eluate from the silica used in the pre-treating step. Dilution of the extracted DNA showed that some DNA was detectable in the silica eluates, suggesting that the DNA content may be higher but signal may be suppressed by co- eluting assay inhibitors. At the lower GTC concentrations no significant loss of total DNA was apparent in the Qubit measurements. Some loss was observed at the higher GTC + isopropanol combinations, e.g., .1.5M GTC with 13.9% isopropanol; 2.03M GTC with 10% isopropanol; and 2.03M GTC with 13.9% isopropanol. EXAMPLE 3 Silica titration PVPP-treated clarified supernatants as described in Example 1 were used to assess the effect of treating the clarified supernatant with different amounts of silica prior to the Qiagen or magnetic bead-binding extractions described above. For each pre-treating test, 1 mL of clarified stool supernatant was combined with 25, 50, 100, or 200 mg of silica gel (non-magnetic) in a volume of 7.2 mL of a pre-treating buffer at PATENT Attorney Docket No: EXCT-42343.601 final concentrations of 1M guanidine thiocyanate with 13.9% isopropanol. For comparison, a pre-treating step was conducted on another 1 mL aliquot of clarified stool supernatant but using 600 µL of the paramagnetic binding beads (16 mg / mL paramagnetic silica beads) in a volume of 12.7 mL of a binding solution having final concentrations of 2.03M guanidine thiocyanate with 10% isopropanol. The samples were incubated at room temperature with shaking at 400 rpm for 1 hour. The silica gel was removed by centrifugation as described above, and the magnetic beads were removed using a magnet, with the supernatants transferred to fresh tubes. The removed silica gel and magnetic beads were washed 4X with wash buffer comprising 20 mM Tris, 0.0125% sodium azide, and 75% isopropanol, dried, and eluted with 200 µL 10 mM Tris HCl pH 8.0, 0.1 mM EDTA to determine whether nucleic acid was lost to the silica gel or magnetic particle binding during the pre-treatment step. Nucleic acids were extracted from 1.0 mL aliquots of the pre-treated stool supernatants. Each aliquot was combined with 6.0 mL of 3.09M guanidine thiocyanate and 21.21% isopropanol and 300 µL magnetic binding beads (16 mg / mL paramagnetic silica beads) and brought to a total volume of 19.8 mL with a binding buffer resulting in final concentrations of 2.03M guanidine thiocyanate and 20% isopropyl alcohol. Aliquots of untreated clarified supernatant were included as controls. The mixtures were incubated at room temperature for 1 hour with shaking at 400 rpm. The tubes were placed on a magnet to separate the beads, and the supernatant fluid was discarded. The beads were resuspended in 900 µL of 2.83M guanidine thiocyanate and 27.9% isopropanol, incubated with shaking for 2 min., then washed 4 times with a wash buffer comprising 20 mM Tris, 0.0125% sodium azide, and 75% isopropanol. The washed beads were dried for 20 min. at 55°C, and the nucleic acid was then eluted with 100 µL of 10 mM Tris-HCl pH 8.0, 0.1 mM EDTA. The resulting samples were analyzed for DNA concentration using Qubit fluorometric quantification (ThermoFisher Scientific). Amounts of the same specific target DNAs used in Example 1 were assayed using the LQAS assay (Exact Sciences) as described in Example 1. The results shown in Figs.9-12. PATENT Attorney Docket No: EXCT-42343.601 These data show that increasing the amount of silica used in the pre-treating step increased both the total DNA yield as measured by Qubit, and the yield of the individual marker DNAs, as detected using the LQAS assays. Additionally, the higher amounts of silica gel gave higher yields of DNA than the magnetic binding beads. Referring to the lower half of Fig.9, it is notable that the magnetic beads also exhibited greater loss of DNA to pre-treatment under these conditions than did the silica gel, as measured by LQAS. In particular, the eluates from the magnetic beads (BND BDS) used in the pre- treatment showed greater signals from Marker DNAs 1, 2, and 3 in the LQAS assay. However, the Qubit measurements showed similar amounts of total DNA eluted from the magnetic beads and the silica gel, suggesting that the apparent difference in DNA in LQAS assays of these eluates may also be due to greater inhibition of LQAS from the silica gel eluates, rather than reflecting less DNA bound to the silica gel during the pre-treatment step. EXAMPLE 4 Detection of Nucleic Acid Markers in Stool Dispersed stool samples were obtained and nucleic acid recovery was evaluated with and without a silica pre-clearing step. The pre-clearing step was conducted at room temperature and elevated temperatures (e.g. greater than 30°C) to determine the effect of temperature on nucleic acid recovery. Nucleic acid recovery was evaluated by LQAS. For Marker 1, Marker 2, and Marker 3, low recovery was observed when the silica pre-clearing step was not performed. Recovery was significantly improved after silica pre-clearing performed at both room temperature and elevated temperatures, with the greatest recovery seen when silica pre-clearing was performed at elevated temperatures (data not shown). EXAMPLE 5 Methods for Parallel Detection of DNA Markers and RNA Markers in Stool Dispersed stool samples may be evaluated in parallel for DNA markers and RNA markers. For example, separate aliquots from the stool sample (e.g., separate fluid fractions from PATENT Attorney Docket No: EXCT-42343.601 the stool sample) may be used for assessment of DNA markers and assessment of RNA markers. Parallel methods for DNA and RNA markers may be conducted by treating portions of stool in dispersing fluid with a silica adsorption matrix and a chaotropic agent, followed by removing or separating the silica adsorption matrix to produce pre-treated fluid samples comprising the nucleic acids. In some embodiments, the conditions of the incubation step (e.g., incubation time, temperature, type(s) of adsorbents, etc.) may be separately optimized for recovery of DNA and RNA. EXAMPLE 6 Methods for Parallel Detection of RNA Markers and Protein Markers in Stool Dispersed stool samples may be evaluated in parallel for RNA markers and protein markers. For example, separate aliquots from the stool sample (e.g., separate aliquots of dispersed sample) may be used for assessment of RNA markers and assessment of protein markers, respectively. Evaluation of RNA markers may be conducted by treating fluid samples, e.g., a stool homogenate as described above or a fluid fraction thereof, with a silica adsorption matrix in a binding solution comprising a chaotropic agent to produce a pre-treated fluid sample comprising RNA. Evaluation of protein markers may be conducted by collecting a supernatant or filtrate from a stool homogenate as described above, e.g., by centrifugation or filtration, treating the supernatant or filtrate with insoluble PVPP particles, and filtering to remove the particles and any residual stool solids, as described in Example 1. The resulting fluid sample is tested for one or more protein markers, e.g., by immunochemical assay. Optionally, the treated fluid sample is diluted, e.g., 1:4, prior to assaying the fluid sample for proteins. In another embodiment, assaying protein markers may be conducted by collecting a supernatant or filtrate from a stool homogenate and testing the supernatant or filtrate for one or more protein markers, e.g., by immunochemical assay. EXAMPLE 7 Methods for Parallel Detection of RNA, DNA, and Protein Markers in Stool PATENT Attorney Docket No: EXCT-42343.601 Dispersed stool samples may be evaluated in parallel for RNA, DNA, and protein markers. For example, aliquots from the stool sample (e.g., multiple dispersed samples) may be used for assessment of RNA, DNA, and protein markers, as described above in Examples 1 and 6. Optionally, the sample may be treated with a methylation-specific reagent prior to assaying the DNA for a methylation state of a target DNA analyte. All literature and similar materials cited in this application, including but not limited to, patents, patent applications, articles, books, treatises, and internet web pages are expressly incorporated by reference in their entirety for any purpose. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which the various embodiments described herein belongs. When definitions of terms in incorporated references appear to differ from the definitions provided in the present teachings, the definition provided in the present teachings shall control. Various modifications and variations of the described compositions, methods, and uses of the technology will be apparent to those skilled in the art without departing from the scope and spirit of the technology as described. Although the technology has been described in connection with specific exemplary embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in pharmacology, biochemistry, medical science, or related fields are intended to be within the scope of the following claims. The scope of the present disclosure is not intended to be limited by the specific disclosures of preferred embodiments in this section or elsewhere in this specification, and may be defined by claims as presented in this section or elsewhere in this specification or as presented in the future. The language of the claims is to be interpreted broadly based on the language employed in the claims and not limited to the examples described in the present specification or during the prosecution of the application, which examples are to be construed as non-exclusive. Features, materials, characteristics, or groups described in conjunction with a particular aspect, embodiment, or example are to be understood to be applicable to any other aspect, embodiment or example described in this section or elsewhere in this specification unless PATENT Attorney Docket No: EXCT-42343.601 incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The protection is not restricted to the details of any foregoing embodiments. The protection extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. Furthermore, certain features that are described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations, one or more features from a claimed combination can, in some cases, be excised from the combination, and the combination may be claimed as a subcombination or variation of a subcombination. Moreover, while operations may be depicted in the drawings or described in the specification in a particular order, such operations need not be performed in the particular order shown or in sequential order, or that all operations be performed, to achieve desirable results. Other operations that are not depicted or described can be incorporated in the example methods and processes. For example, one or more additional operations can be performed before, after, simultaneously, or between any of the described operations. Further, the operations may be rearranged or reordered in other implementations. Those skilled in the art will appreciate that in some embodiments, the actual steps taken in the processes illustrated and / or disclosed may differ from those shown in the figures. Depending on the embodiment, certain of the steps described above may be removed, others may be added. Furthermore, the features and attributes of the specific embodiments disclosed above may be combined in different ways to form additional embodiments, all of which fall within the scope of the present disclosure. For purposes of this disclosure, certain aspects, advantages, and novel features are described herein. Not necessarily all such advantages may be achieved in accordance with any particular embodiment. Thus, for example, those skilled in the art will recognize that the PATENT Attorney Docket No: EXCT-42343.601 disclosure may be embodied or carried out in a manner that achieves one advantage or a group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.

Claims

PATENT Attorney Docket No: EXCT-42343.601 CLAIMS What is claimed is:

1. A method of removing at least one interfering compound from a fluid sample comprising or suspected of comprising nucleic acids, the method comprising: a) combining at least a portion of a fluid sample with a silica adsorption matrix and a chaotropic agent in a mixture, wherein an interfering compound, if present in the fluid sample, is bound to the silica adsorption matrix; and b) removing or separating the silica adsorption matrix from the mixture to produce a pre-treated fluid sample comprising nucleic acids.

2. The method of claim 1, wherein the mixture further comprises at least one alcohol.

3. The method of claim 1, wherein the chaotropic agent comprises one or more of guanidine thiocyanate, guanidine isothiocyanate, and guanidine HCl.

4. The method of claim 1, wherein the chaotropic agent is present in the mixture in a concentration of about 2M, preferably ≤ 2M, preferably ≤ 1.9M, preferably ≤ 1.8M, preferably ≤ 1.7M, preferably ≤ 1.6M, preferably ≤ 1.5M, preferably ≤ 1.4M, preferably ≤ 1.3M, preferably ≤ 1.2M, preferably ≤ 1.1M.

5. The method of claim 1, wherein the chaotropic agent is present in the mixture in a concentration of ≥ 0.1M, preferably ≥ 0.2M, preferably ≥ 0.3M, preferably ≥ 0.4M, preferably ≥ 0.5M, preferably ≥ 0.6M, preferably ≥ 0.7M, preferably ≥ 0.8M, preferably ≥ 0.9M, preferably about 1.0M.

6. The method of claim 2, wherein the alcohol is selected from short-chain branched or unbranched alkanols having from 1 to 5 carbon atoms, preferably comprising methanol, ethanol, propanol, isopropanol, butanols or pentanols, or mixtures thereof.PATENT Attorney Docket No: EXCT-42343.601 7. The method of claim 2, wherein the alcohol is present in the mixture in a concentration of ≥1% (v / v), preferably ≥2% (v / v), preferably ≥3% (v / v), preferably ≥4% (v / v), preferably ≥5% (v / v) preferably ≥6% (v / v) preferably ≥7% (v / v) preferably ≥8% (v / v) preferably ≥9% (v / v) preferably ≥10% (v / v) preferably ≥11% (v / v) preferably ≥12% (v / v) preferably ≥13% (v / v) preferably ≥14% (v / v).

8. The method of claim 1, wherein the silica adsorption matrix in the mixture is at least 0.1 mg / mL, preferably ≥0.2 mg / mL, preferably ≥0.3 mg / mL, preferably ≥0.4 mg / mL, preferably ≥0.5 mg / mL, preferably ≥0.6 mg / mL, preferably ≥0.7 mg / mL, preferably ≥0.8 mg / mL, preferably ≥0.9 mg / mL, preferably ≥1.0 mg / mL, preferably ≥1.1 mg / mL, preferably ≥1.2 mg / mL, preferably ≥1.3 mg / mL, preferably ≥1.4 mg / mL, preferably ≥1.5 mg / mL, preferably ≥1.6 mg / mL, preferably ≥1.7 mg / mL, preferably ≥1.8 mg / mL, preferably ≥1.9 mg / mL, preferably ≥2.0 mg / mL, preferably ≥2.1 mg / mL, preferably ≥2.2 mg / mL, preferably ≥2.3 mg / mL, preferably ≥2.4 mg / mL, preferably ≥2.5 mg / mL, preferably ≥2.6 mg / mL, preferably ≥2.7 mg / mL, preferably ≥2.8 mg / mL, preferably ≥2.9 mg / mL, preferably ≥3.0 mg / mL, preferably ≥3.1 mg / mL, preferably ≥3.2 mg / mL, preferably ≥3.3 mg / mL, preferably ≥3.4 mg / mL, preferably ≥3.5 mg / mL, preferably ≥3.6 mg / mL, preferably ≥3.7 mg / mL, preferably ≥3.8 mg / mL, preferably ≥3.9 mg / mL, preferably ≥4.0 mg / mL, preferably ≥4.1 mg / mL, preferably ≥4.2 mg / mL, preferably ≥4.3 mg / mL, preferably ≥4.4 mg / mL, preferably ≥4.5 mg / mL, preferably ≥4.6 mg / mL, preferably ≥4.7 mg / mL, preferably ≥4.8 mg / mL, preferably ≥4.9 mg / mL, preferably ≥5.0 mg / ml, preferably ≥10 mg / ml, preferably ≥15 mg / ml, preferably ≥20 mg / ml, preferably ≥25 mg / ml, preferably ≥30 mg / mL, preferably ≥35 mg / mL, preferably ≥40 mg / mL, preferably ≥45 mg / mL, preferably ≥50 mg / mL, preferably ≥55 mg / mL, preferably ≥60 mg / mL, preferably ≥65 mg / mL, preferably ≥70 mg / mL, preferably ≥75 mg / mL, preferably ≥80 mg / mL, preferably ≥85 mg / mL, preferably ≥90 mg / mL, preferably ≥95 mg / mL, preferably ≥100 mg / mL, or any fractional concentration therebetween.

9. The method of any one of claims 1-8, wherein prior to step a) the fluid sample has an amount of total nucleic acid, and wherein the silica adsorption matrix removed or separated from the mixture comprises less than half the amount of total nucleic acid present in the fluid sample,PATENT Attorney Docket No: EXCT-42343.601 preferably less than 40%, preferably less than 30%, preferably less than 20%, preferably less than 10%, preferably less than 5%, preferably less than 1% present in the fluid sample.

10. The method of claim 9, wherein the silica adsorption matrix removed or separated from the mixture is substantially free of nucleic acid.

11. The method of claim 1, wherein the silica adsorption matrix comprises beads or particles composed of or coated with silica.

12. The method of any one of claims 1-11, wherein the silica adsorption matrix comprises one or more of SiO2crystals, skeletons of diatoms built up from SiO2, amorphous silicon oxide, glass powder, silica gel, glass, zeolite, silica-coated beads, particles, paramagnetic particles, boron silicates, aluminum silicates, phosphosilicates, silica carbonyl, silica sulfonyl and silica phosphonyl surfaces.

13. The method of any one of claims 1-12, wherein the removing or separating comprises at least one of filtration and centrifugation.

14. The method of any one of claims 1-13, further comprising, prior to step a), providing a fluid sample.

15. The method of claim 14, wherein providing the fluid sample comprises dispersing a sample in a dispersing fluid.

16. The method of claim 15, wherein the dispersing fluid and the sample are combined in a ratio, wherein the ratio of dispersing fluid-to-sample is no more than 1:1 (v:v or v:w).

17. The method of claim 15, wherein the dispersing fluid and the sample are combined in a ratio, wherein the ratio of dispersing fluid-to-sample is between 1:1 and 1000:1 (v:v or v:w).PATENT Attorney Docket No: EXCT-42343.601 18. The method of claim 17, wherein the ratio of dispersing fluid-to-sample is 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, 200:1, 300:1, 400:1, 500:1, or 1000:1, including any fractional amount therebetween.

19. The method of any one of claims 1-18, wherein the fluid sample has a volume between 0.1 mL and 1000 mL.

20. The method of claim 19, wherein the volume of the fluid sample is from 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8.1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, to 1000 mL, including any fractional amount therebetween.

21. The method of any one of claims 1-18, wherein the fluid sample has a volume of more than 1000 mL.

22. The method of any one of claims 14-21, further comprising prior to step a), partitioning a dispersed sample into a solids fraction and a fluid fraction, wherein the fluid sample comprises at least a portion of the fluid fraction from the dispersed sample.

23. The method of claim 22, wherein the fluid in the dispersed sample is a dispersing fluid.

24. The method of claim 22, wherein the dispersed sample is selected from a bodily fluid, a homogenate, and a suspension.

25. The method of claim 22, further wherein providing the dispersed sample comprises dispersing sample material that is at least partially solid or semisolid in a dispersing fluid.PATENT Attorney Docket No: EXCT-42343.601 26. The method of claim 25, wherein the sample material comprises one or more of: human or animal tissues, bone marrow, plants, plant parts and extracts, fungi, microorganisms, fossil or mummified specimens, soil samples, sewage sludge, wastewater, stool, or foodstuffs.

27. The method of any one of claims 23-26, wherein the dispersing fluid comprises one or more of: i) a chaotropic agent; ii) an alcohol; iii) a detergent; iv) a salt; v) a preservative; vi) a buffering agent; vii) a protein; viii) a protoporphyrin IX complex; ix) a nuclease inhibitor; x) a nuclease; xi) a chelating agent; xii) a protease; and xiii) a protease inhibitor.

28. The method of claim 27, wherein the dispersing fluid comprises a buffering agent, and one or more of i)-v) and vii)-xiii).

29. The method of claim 27 or 28, wherein the dispersing fluid comprises one or more buffering agents selected from HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (N-morpholino)propanesulfonic acid), a phosphate buffer, and TRIS (Tris(hydroxymethyl)aminomethane).PATENT Attorney Docket No: EXCT-42343.601 30. The method of any one of claims 27-29, wherein the dispersing fluid comprises three or more of i)-xiii).

31. The method of claim 30, wherein the dispersing fluid comprises three or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex.

32. The method of claim 30, wherein the dispersing fluid comprises four or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex.

33. The method of claim 30, wherein the dispersing fluid comprises a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex.

34. The method of any one of claims 1-33, wherein the interfering compound comprises one or more of a polyphenol, a polysaccharide, a humic substance, an enzymatic inhibitor from soil, a humic polymer, an organic compound from compost, a decomposing plant material, a plant pigment, a plant cell wall, a chitin, a photosynthetic pigment, a humic acid, a fulvic acid, a phenolic polymer and / or phenolic oligomer, a tannin, a humic, and a phenolic compound.

35. The method of any one of claims 1-34, characterized by at least one of: a) the fluid sample comprising or suspected of comprising nucleic acids comprises DNA and RNA; b) the fluid sample comprising or suspected of comprising nucleic acids comprises DNA; c) the fluid sample comprising or suspected of comprising nucleic acids comprises RNA; d) the fluid sample comprising or suspected of comprising nucleic acids comprises single stranded nucleic acids; e) the fluid sample comprising or suspected of comprising nucleic acids comprises double-stranded nucleic acids; f) the fluid sample comprising or suspected of comprising nucleic acids comprises double-stranded DNA and / or double-stranded RNA;PATENT Attorney Docket No: EXCT-42343.601 g) the fluid sample comprising or suspected of comprising nucleic acids comprises heteroduplexed DNA and RNA; h) the fluid sample comprising or suspected of comprising nucleic acids comprises cell-free nucleic acids; and i) the fluid sample comprising or suspected of comprising nucleic acids comprises a protein analyte.

36. The method of any one of claims 1-35, further comprising extracting nucleic acids from the pre-treated fluid sample.

37. The method of claim 36, further comprising measuring an expression level of an RNA molecule of the extracted nucleic acids.

38. The method of claim 36, further comprising assaying a nucleic acid for one or more sequence variations selected from a sequence polymorphism, an insertion, a deletion, and a nucleotide mutation.

39. The method of claim 36, further comprising treating the nucleic acids with a methylation- specific reagent.

40. The method of claim 39, further comprising measuring a methylation state of a DNA molecule of the treated nucleic acids.

41. The method of any one of claims 1-40, further comprising treating the fluid sample or the pre-treated fluid sample with an assay inhibitor adsorbant.

42. The method of claim 41, wherein the assay inhibitor adsorbant comprises polyvinylpyrrolidone.

43. The method of claim 42, wherein the polyvinylpyrrolidone is in an insoluble form.PATENT Attorney Docket No: EXCT-42343.601 44. The method of claim 43, wherein the insoluble form comprises polyvinylpolypyrrolidone.

45. The method of any one of claims 41-44, wherein treating the fluid sample or the pre- treated fluid sample with an assay inhibitor adsorbant comprises removing the assay inhibitor adsorbant from the fluid sample or the pre-treated fluid sample.

46. The method of claim 45, wherein the removing comprises centrifugation and / or filtration.

47. The method of any one of claims 41-46, wherein the assay inhibitor adsorbant is added to and removed from the fluid sample prior to step a).

48. The method of any one of claims 41-46, wherein step a) further comprises adding the assay inhibitor adsorbant to the fluid sample in the mixture, and wherein step b) further comprises removing or separating the assay inhibitor adsorbant from the mixture.

49. The method of any one of claims 41-46, wherein the assay inhibitor adsorbant is added to and removed from the pre-treated fluid sample after step b).

50. The method of any one of claims 1-49, wherein the pH of a binding solution comprising the chaotropic agent and / or of the mixture is from about 2 to 10, preferably from about 7-9, more preferably from about 7-8.

51. The method of any one of claims 1-50, further comprising assaying at least a portion of the fluid sample for one or more proteins.

52. The method of claim 51, wherein the one or more proteins comprise hemoglobin.

53. The method of any one of claims 1-52, further comprising one or both of: a) heating at least a portion of the fluid sample prior to step a); and b) heating the mixture prior to step b).PATENT Attorney Docket No: EXCT-42343.601 54. A method for assaying analytes in a stool sample, the method comprising: a) treating a first portion of a dispersed sample to produce a solids fraction and a first fluid fraction, and assaying the first fluid fraction for one or more proteins; and b) assaying nucleic acid extracted from a second portion of the dispersed sample for one or more nucleic acid marker analytes.

55. The method of claim 54, comprising before step b), treating a second portion of the dispersed sample with silica to form a treated second portion, wherein assaying nucleic acid extracted from a second portion of the dispersed sample comprises assaying nucleic acid extracted from the treated second portion.

56. The method of claim 55, wherein treating the second portion of the dispersed sample with silica comprises: a) combining the second portion of the dispersed sample with a silica adsorption matrix and a chaotropic agent in a mixture, wherein an interfering compound, if present in the dispersed sample, is bound to the silica adsorption matrix; and b) removing or separating the silica adsorption matrix from the mixture to produce a pre-treated fluid sample comprising nucleic acids.

57. The method of claim 56, further comprising treating one or more of the dispersed sample, the first portion of the dispersed sample, the first fluid fraction, the second portion of the dispersed sample and / or the pre-treated fluid sample with an assay inhibitor adsorbant.

58. The method of claim 57, wherein the assay inhibitor adsorbant comprises polyvinylpyrrolidone.

59. The method of claim 58, wherein the polyvinylpyrrolidone is in an insoluble form.

60. The method of claim 59, wherein the insoluble form comprises polyvinylpolypyrrolidone.PATENT Attorney Docket No: EXCT-42343.601 61. The method of any one of claims 57-60, wherein treating the dispersed sample, the first portion of the dispersed sample, the first fluid fraction, the second portion of the dispersed sample and / or the pre-treated fluid sample with an assay inhibitor adsorbant comprises removing the assay inhibitor adsorbant from the dispersed sample, the first portion of the dispersed sample, the first fluid fraction, the second portion of the dispersed sample and / or the pre-treated fluid sample.

62. The method of claim 61, wherein the removing comprises centrifugation and / or filtration.

63. A reagents kit for extraction of nucleic acids contained in samples, comprising one or more of: (a) a solution suitable for taking up a sample to form a homogenate, (b) a silica matrix for binding interfering compounds in a fluid fraction from the homogenate; and optionally (c) reagents and / or devices for extracting nucleic acid from a pre-treated fluid sample.

64. The reagents kit of claim 63, further comprising instructions for extracting the nucleic acids, optionally wherein the nucleic acids are DNA, RNA, or both.

65. The reagents kit of claim 63 or 64, wherein the solution comprises a dispersing fluid.

66. The reagents kit of claim 65, wherein the dispersing fluid comprises one or more of: i) a chaotropic agent; ii) an alcohol; iii) a detergent; iv) a salt; v) a preservative; vi) a buffering agent; vii) a protein; viii) a protoporphyrin IX complex; ix) a nuclease inhibitor;PATENT Attorney Docket No: EXCT-42343.601 x) a nuclease; xi) a chelating agent; xii) a protease; and / or xiii) a protease inhibitor.

67. The reagents kit of claim 66, wherein the dispersing fluid comprises a buffering agent, and one or more of i)-v) and vii)-xiii).

68. The reagents kit of claim 66 or 67, wherein the dispersing fluid comprises one or more buffering agents selected from HEPES, PIPES, MES, MOPS, a phosphate buffer, and TRIS.

69. The reagents kit of any one of claims 66-68, wherein the dispersing fluid comprises three or more of i)-xiii).

70. The reagents kit of claim 69, wherein the dispersing fluid comprises three or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex.

71. The reagents kit of claim 69, wherein the dispersing fluid comprises four or more of a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex.

72. The reagents kit of claim 66, wherein the dispersing fluid comprises a detergent, a salt, a preservative, a buffering agent, a protein, and a protoporphyrin IX complex.

73. The reagents kit of any one of claims 63-72, further comprising an assay inhibitor adsorbant.

74. The reagents kit of claim 73, wherein the assay inhibitor adsorbant comprises polyvinylpyrrolidone.

75. The reagents kit of claim 74, wherein the polyvinylpyrrolidone is in an insoluble form.PATENT Attorney Docket No: EXCT-42343.601 76. The reagents kit of claim 75, wherein the insoluble form comprises polyvinylpolypyrrolidone.

77. A system for removing at least one interfering compound from a fluid sample comprising or suspected of comprising nucleic acids, the system comprising the reagents kit of any one of claims 63-76.

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