Systems and methods for detection of cancer using fatty acids

Abstract

The present disclosure generally relates to systems and methods for detection of cancer or other diseases even, in some cases, before the disease is clinically manifest. In some aspects, reactive oxygen species (e.g., superoxides, hydroxyls, peroxides, etc.) may react with fatty acids or other lipids, e.g., in the blood of a subject. In some cases, the reactive oxygen species may be affected by the presence of cancer cells, or other disease states, which often result in altered metabolic states. Accordingly, by determining or analyzing fatty acids in a subject, e.g., the presence of, concentration of, or metabolic reactions involving fatty acids in the blood of a subject, the health of the subject may be determined. In some cases, such determinations may be augmented, for example, by providing fatty acids to a subject and analyzing any concentrations or reactions that deviates from normative values.

Description

[0001] SYSTEMS AND METHODS FOR DETECTION OF CANCER USING FATTY ACIDS

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 622,467, filed January 18, 2024, entitled “Systems and Methods for Detection of Cancer Using Fatty Acids,” by Fossel, incorporated herein by reference in its entirety.

[0004] FIELD

[0005] The present disclosure generally relates to systems and methods for detection of cancer or other diseases even, in some cases, before the disease is clinically manifest.

[0006] BACKGROUND

[0007] Cancer is what is known as a clonal disease. That is, it starts with a single cell and grows as the cells proliferate. The body is prepared to attack nascent cancers by a mechanism known as immune surveillance. As soon as the immune system recognizes that an abnormal cell is present, it tries to kill it. This happens through a pathway that results in production of Reactive Oxygen Species (ROS), which are highly reactive and short-lived oxygen radicals. These ROS react with many things in the plasma, including the plasma lipids of lipoproteins, which may alter the distribution and composition of these lipoprotein lipids. This activity is thought to begin at the earliest presence of cancer and continue as the cancer is first suppressed by this process. If the cancer cells eventually grow faster than this process can suppress, this may result in clinically manifest cancer.

[0008] SUMMARY

[0009] The present disclosure generally relates to systems and methods for detection of cancer or other diseases even, in some cases, before the disease is clinically manifest. In some cases, these may improve over many known approaches that require the disease being clinically manifest before diagnosis. The subject matter of the present disclosure involves, in some cases, interrelated products, alternative solutions to a particular problem, and / or a plurality of different uses of one or more systems and / or articles. Various embodiments can employ some, all, or any combination of the disclosed features, functions, steps, and / or algorithms.

[0010] One aspect is generally directed to a simple method. In one set of embodiments, the article comprises a system of interactive methods and steps, or a system configured to execute a set of interactive method and steps. In another set of embodiments, the system comprises a group of methods performed sequentially or in a particular pattern of applying the group of methods in a non- sequential manner. Some embodiments are directed to a method with tailored model with a minimal number of classes for identifying cancer cells according to a predicted probability.

[0011] The disclosed functions, steps, and / or algorithms can be executed sequentially, in parallel, according to a pattern, and / or under supervision.

[0012] Several methods are disclosed herein that are directed to diagnose or treat various types of cancer. Other methods are disclosed herein which are particular to an individual type of cancer. It is to be understood that in each such aspect of the invention, some embodiments may use a single analytical method, and in other embodiments, multiple analytical methods may be used, e.g., sequentially or simultaneously. In further embodiments, respective output from individual analysis can be combine or used together to improve the confidence in a prediction identifying cancer cells or to provide an improved probability associated with a cancer diagnosis. In some examples, the predive models are tailored to small and / or incomplete data sets, that return probability determination with a greater degree of accuracy that many conventional systems.

[0013] Several methods are disclosed herein of administering a subject with a compound for prevention or treatment of a particular condition. It is to be understood that in each such aspect of the disclosure, the disclosure specifically includes, also, the compound for use in the treatment or prevention of that particular condition, as well as use of the compound for the manufacture of a medicament for the treatment or prevention of that particular condition.

[0014] One aspect is generally directed to a method. In one set of embodiments, the method is directed to a method of treating a subject suspected of having cancer. In one embodiment, the method comprises administering a plurality of fatty acids to a subject; withdrawing blood from the subject; determining a concentration of each of the plurality of fatty acids in the blood; for each of the plurality of unsaturated fatty acids, determining a cancer probability to the unsaturated fatty acid using a probabilistic classifier; and treating the subject for cancer based on the cancer probabilities.

[0015] The method, in another embodiment, comprises determining a concentration of each of a plurality of fatty acids in the blood; for each of the plurality of unsaturated fatty acids, determining a cancer probability to the unsaturated fatty acid using a probabilistic classifier; and treating the subject for cancer based on the cancer probabilities.

[0016] In another set of embodiments, the method comprises administering a plurality of fatty acids to a subject; withdrawing blood from the subject; determining a concentration of each of the plurality of fatty acids in the blood; and for each of the plurality of fatty acids, determining a cancer probability to the unsaturated fatty acid using a probabilistic classifier. In some cases, some or all of the fatty acids may be saturated fatty acids, or unsaturated fatty acids.

[0017] In some cases, the probability classifier may be trained using data on blood or other biological samples taken from subjects that later develop cancer symptoms, e.g., several months or years after the blood or other biological sample was taken. In some case, relatively small numbers of subjects may be used, e.g., less than 10,000, less than 5,000 less than 1,000, less than 500, or less than 100 subjects.

[0018] In another set of embodiments, the method is an in vitro method. In one set of embodiments, the method comprises determining a concentration of a plurality of fatty acids in an aqueous solution; and for each of the plurality of fatty acids within the aqueous solution, assigning a probability score to the unsaturated acid using a probabilistic classifier. The probability score may reflect the presence or likelihood of cancer or another disease. In some cases, some or all of the fatty acids may be saturated fatty acids, or unsaturated fatty acids.

[0019] Another aspect is generally drawn to a composition. In one set of embodiments, the composition comprises a liquid comprising at least 10 fatty acids, each at a concentration of at least 10 mmol / L, including the fatty acids linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9, 11 -octadecadienoic acid, and 10,12-octadecadienoic acid.

[0020] In another set of embodiments, the composition comprises a liquid comprising at least 10 unsaturated fatty acids, each unsaturated fatty acid having a mass of at least 1 g, including the fatty acids linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9, 11 -octadecadienoic acid, and 10,12-octadecadienoic acid.

[0021] In another aspect, the present disclosure encompasses methods of making one or more of the embodiments described herein. In still another aspect, the present disclosure encompasses methods of using one or more of the embodiments described herein. Other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments of the disclosure when considered in conjunction with the accompanying figures.

[0022] BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Non-limiting embodiments of the present disclosure will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the disclosure shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure. In the figures:

[0024] Fig. 1 illustrates Gaussian Naive Bayes, in accordance with one embodiment;

[0025] Fig. 2 illustrates model evaluation, according to another embodiment;

[0026] Fig. 3 is a schematic illustrating model selection, in another embodiment;

[0027] Figs. 4A-4B illustrate data for subjects having lung or ovarian cancer, in yet another embodiment;

[0028] Fig. 5 illustrates fatty acids with different DOR values, in still another embodiment;

[0029] Fig. 6 is a table listing abbreviations for various fatty acids; and

[0030] Fig. 7 is a block diagram of an example special purpose computer system improved by the functions and / or processes disclosed herein.

[0031] DETAILED DESCRIPTION

[0032] The present disclosure generally relates to systems and methods for detection of cancer or other diseases even, in some cases, before the disease is clinically manifest. In some aspects, reactive oxygen species (e.g., superoxides, hydroxyls, peroxides, etc.) may react with fatty acids or other lipids, e.g., in the blood of a subject. In some cases, the reactive oxygen species may be affected by the presence of cancer cells, or other disease states, which often result in altered metabolic states. Accordingly, by determining or analyzing fatty acids in a subject, e.g., the presence of, concentration of, or metabolic reactions involving fatty acids in the blood of a subject, the health of the subject may be determined. In some cases, such determinations may be augmented, for example, by providing fatty acids to a subject and analyzing any concentrations or reactions that deviates from normative values. The fatty acids within the subject may be assessed, for example, using probabilistic classifiers such as Gaussian Naive Bayesian analysis, to determine the probability that the subject has cancer or another disease, and if warranted, suitable treatments may be applied to the subject. In various embodiments, the disclosed models are specially tailored to generate classification in probabilistic spaces having small data population or limited training data spaces.

[0033] Thus, for example, certain embodiments generally relate to detection or treatment of cancer in a subject, including the detection of cancer prior to clinical presentation. This includes various aspects, which may be used separately or together. In one embodiment, for instance, blood plasma can be obtained from a subject being tested, and procedures to determine the presence or absence of cancer are carried out, e.g., as discussed herein. Any suitable sample may be taken from the subject, including blood, saliva, urine, or the like. In some cases, for example, blood may be obtained from a subject, and analyzed as discussed herein. In other cases, the blood may first be processed, e.g., to produce blood plasma or serum, which can then be analyzed as discussed herein. After analysis, the subject may also be treated for the cancer, e.g., if the subject is determined to have cancer.

[0034] A “subject,” as used herein, means a human, or non-human animal. Examples of subjects include, but are not limited to, a mammal such as a cow, sheep, goat, horse, rabbit, pig, mouse, rat, dog, cat, a primate (e.g., a monkey, a chimpanzee, etc.), or the like. In some cases, the subject is a non-mammal such as a bird, an amphibian, or a fish. In some embodiments, the subject is genetically engineered.

[0035] In some aspects, one or more fatty acids may optionally be administered to a subject, e.g., fed to the subject. Other methods of administration that may be used in various embodiments include parenteral, intramuscular, intranasal, sublingual, intratracheal, inhalation, ocular, vaginal, intravenously, percutaneously, and rectal. In some cases, intramuscular administration is used. In one set of embodiments, intravenous administration is used. However, it should be understood that in other embodiments, additional fatty acids need not be administered to a subject. In some embodiments, the reactivity of fatty acids already present in the blood or fluid can be analyzed to determine the probability of cancer or other diseases.

[0036] The one or more fatty acids may be administered to a subject, e.g., simultaneously and / or sequentially. The fatty acids may be saturated fatty acids and / or unsaturated fatty acids. Typically, the unsaturated fatty acid may include at least one double bond and / or at least one triple bond within a fatty acid chain of the fatty acid. For example, the unsaturated fatty acid may include one, two, or more double bonds; the unsaturated fatty acid may include one, two, or more triple bonds; or a combination of these. In some cases, the fatty acids may be a relatively small-chain fatty acid. For example, a fatty acid may have 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms.

[0037] Non-limiting examples of such unsaturated fatty acids include C3, C4, Cs, Ce, C7, and Cs fatty acids. These may include monounsaturated and / or polyunsaturated fatty acids. Specific examples include, but are not limited to, CH2=CHCOOH, CH3CH=CHCOOH, CH3CH2CH=CHCOOH, CH3CH2CH2CH=CHCOOH, CH2=CHCH2COOH, CH2=CH CH2CH2COOH, CH2=CHCH2CH2CH2COOH, CH2=CHCH2CH=CHCOOH, CH2=CHCH=CHCOOH, etc. In addition, in some cases, the fatty acids may come from naturally occurring sources, such as krill oil, fish oil, safflower oil, soybean oil, flaxseed oil, canola oil, algal oil, etc.

[0038] Other examples of unsaturated fatty acids includes one or more of octanoic acid, decanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, docosanoic acid, tricosanoic acid, tetracosanoic acid, 9c-tetradecenoic acid, 10c- pentadecenoic acid, 9c-hexadecenoic acid, 9c-octadecenoic acid, llc-octadecenoic acid, 11c- eicosenoic acid, 15c-tetrasenoic acid, 9c,12c,15c-octadecatrienoic acid, 5c,8c,llc,14cl7c- eicosapentaenoic acid, 7c,10c,13c,16c,19c-docosapentaenoic acid, 4c,7c,10c,13c,16c,19c- docosahexaenoic acid, 9c,12c-octadecadienoic acid, 6c,9c,12c-octadecatrienoic acid, llc,14c-eicosadienoic acid, 8c,llc,14c-eicosatrienoic acid, 5c, 8c, 111c, 14c -eicosatetraenoic acid, 13c,16c-docosadienoic acid, 7c,10c,13c,16c-docosatetraenoic acid, 9t-tetadecenoic acid, 9t-hexadecenoic acid, 6t-octadecenoic acid, 9t-octadecenoic acid, llt-octadecenoic acid, 9t,12t-octadecadienoic acid, 9c,12t-octadecadienoic acid, 9t,12c-octadecadienoic acid, llt- eicosenoic acid, or 9c,llt-octadecadienoic acid. One, more than one, or all of these may be used in various embodiments.

[0039] In some cases, fatty acids supplied to a subject may include one or more of dodecanoic acid, lOc-pentadecenoic acid, arachidonic acid, 6t-octadecenoic acid, l lc- octadecenoic acid, linalolinic acid, nonadecanoic acid, 9t,12t-octadecadienoic acid, 11c- eicosenoic acid, 13c,16c-docosadienoic acid, and 4c,7c,10c,13c,16c,19c-docosahexanenoic acid. In some cases, fatty acids supplied to a subject may include one or more of tetradecanoic acid, 9t,12c-octadecadienoic acid, 9c,12c,15c-octadecatrienoic acid, linolaic acid, 5c,8c,l lc,14c,17c-eicosapentaenoic acid, 7c,10c,13c,16c-docosatetraenoic acid, and 7c,10c,13c,16c,19c-docosapentaenoic acid. Additional non-limiting examples of fatty acids are discussed in more detail herein.

[0040] A wide range of dosing of fatty acids may be used. In some embodiments, fatty acids may be given to a subject, such as a human, at a dosage of at least 0.1 g, at least 0.2 g, at least 0.3 g, at least 0.4 g, at least 0.5 g, at least 0.6 g, at least 0.7 g, at least 0.8 g, at least 0.9 g, at least 1 g, at least 2 g, at least 3 g, at least 4 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g, at least 10 g, at least 11 g, at least 12 g, at least 13 g, at least 14 g, or at least 15 g. In some embodiments, the fatty acids may be given at a dosage of no more than 15 g, no more than 14 g, no more than 13 g, no more than 12 g, no more than 11 g, no more than 10 g, no more than 9 g, no more than 8 g, no more than 7 g, no more than 6 g, no more than 5 g, no more than 4 g, no more than 3 g, no more than 2 g, no more than 1 g, no more than 0.9 g, no more than 0.8 g, no more than 0.7 g, no more than 0.6 g, no more than 0.5 g, no more than 0.4 g, no more than 0.3 g, no more than 0.2 g, or no more than 0.1 g. Combinations of any of these are also possible in some embodiments, e.g., the dosage may be between 1 and 15 g, between 1 and 10 g, between 5 and 10 g, between 0.5 and 1 g, etc. If more than one fatty acid is present, then some or all of the fatty acids may each independently be present in any of the above ranges.

[0041] In some embodiments, the fatty acids may be given to a subject, such as a human, at a dosage of at least 1 mg / kg, at least 2 mg / kg, at least 3 mg / kg, at least 5 mg / kg, at least 10 mg / kg, at least 20 mg / kg, at least 30 mg / kg, at least 50 mg / kg, at least 100 mg / kg, at least 200 mg / kg, at least 300 mg / kg, at least 500 mg / kg, at least 1 g / kg, or at least 2 mg / kg. In some cases, the fatty acids may be given at a dosage of no more than 2 g / kg, no more than 1 g / kg, no more than 500 mg / kg, no more than 300 mg / kg, no more than 200 mg / kg, no more than 100 mg / kg, no more than 50 mg / kg, no more than 30 mg / kg, no more than 20 mg / kg, no more than 10 mg / kg, no more than 5 mg / kg, no more than 3 mg / kg, no more than 2 mg / kg, or no more than 1 mg / kg. Combinations of any of these are also possible in some embodiments, e.g., the dosage may be 1 g / kg to 2 g / kg, 500 mg / kg to 1 g / kg, 400 mg / kg to 800 mg / kg, etc. If more than one fatty acid is present, then some or all of the fatty acids may each independently be present in any of the above ranges. In some embodiments, the fatty acids may be given to a subject, such as a human, in a composition, such as a liquid, tablet, pill, capsule, or the like. In some cases, the fatty acids may each independently be present within the composition administered to the subject at a concentration of at least 1 mmol / L, at least 2 mmol / L, at least 3 mmol / L, at least 5 mmol / L, at least 10 mmol / L, at least 20 mmol / L, at least 30 mmol / L, at least 50 mmol / L, at least 100 mmol / L, at least 200 mmol / L, at least 300 mmol / L, at least 500 mmol / L, at least 1 mol / L, at least 2 mol / L, at least 3 mol / L, at least 5 mol / L, or at least 10 mol / L. In some cases, the fatty acids may be given at a dosage of no more than 10 mol / L, no more than 5 mol / L, no more than 3 mol / L, no more than 2 mol / L, no more than 1 mol / L, no more than 500 mmol / L, no more than 300 mmol / L, no more than 200 mmol / L, no more than 100 mmol / L, no more than 50 mmol / L, no more than 30 mmol / L, no more than 20 mmol / L, no more than 10 mmol / L, no more than 5 mmol / L, no more than 3 mmol / L, no more than 2 mmol / L, or no more than 1 mmol / L. Combinations of any of these are also possible in some embodiments, e.g., the concentration may be 10 mmol / L to 20 mmol / L, 500 mmol / L to 1 mol / L, 400 mmol / L to 800 mmol / L, etc. If more than one fatty acid is present, then some or all of the fatty acids may each independently be present in any of the above ranges.

[0042] In certain cases, the fatty acids may each independently be present within the composition administered to the subject at a mass of at least 1 mg, at least 2 mg, at least 3 mg, at least 5 mg, at least 10 mg, at least 20 mg, at least 30 mg, at least 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 500 mg, at least 1 g, at least 2 g, at least 3 g, at least 5 g, at least 10 g, at least 20 g, at least 30 g, at least 50 g, at least 100 g, at least 200 g, at least 300 g, at least 500 g, etc. In some cases, the fatty acids may be given at a dosage of no more than 500 g, no more than 300 g, no more than 200 g, no more than 100 g, no more than 50 g, no more than 30 g, no more than 20 g, no more than 10 g, no more than 5 g, no more than 3 g, no more than 2 g, no more than 1 g, no more than 500 mg, no more than 300 mg, no more than 200 mg, no more than 100 mg, no more than 50 mg, no more than 30 mg, no more than 20 mg, no more than 10 mg, no more than 5 mg, no more than 3 mg, no more than 2 mg, or no more than 1 mg. Combinations of any of these are also possible in some embodiments, e.g., the mass may be 10 g to 20 g, 50 g to 100 g, 400 g to 800 g, etc. If more than one fatty acid is present, then some or all of the fatty acids may each independently be present in any of the above ranges. After such administration to a subject, a biological sample may be obtained from the subject in accordance with certain aspects, e.g., after a predetermined amount of time, and analyzed as discussed herein, for example, to determine the presence or absence of cancer or other disease, etc. In some cases, the subject may also be treated for the cancer or other disease.

[0043] In some cases, the time between administration of the fatty acids and withdrawal of a biological sample from a subject may be, for example, at least 1 minute, at least 1 hour, at least 12 hours, at least 18 hours, at least 1 day, at least 36 hours, at least 2 days, at least 2.5 days, at least 3 days, etc. This may, for example, allow the fatty acids to interact with reactive oxygen species within the subject.

[0044] In some aspects, one or more fatty acids may be determined within a fluid sample, such as a biological sample, as reactive oxygen species (e.g., superoxides, hydroxyls, peroxides, etc.) may react with fatty acids or other lipids. The fluid sample may be one taken from a subject (e.g., a biological fluid, such as blood), or in some cases, the fluid sample may be artificially created. For example, the fluid sample may be an aqueous solution.

[0045] In some embodiments, certain types of fatty acids are more susceptible to reactive oxygen species than others. Thus, each of the fatty acid concentrations may be individually determined in the sample to determine the probability that a particular fatty acid is indicative of the subject having cancer (or another disease). The fatty acids to be determined may include saturated fatty acids and / or unsaturated fatty acids. In some cases, the concentrations of the fatty acids are determined within the fluid sample, e.g., using techniques such as GC / MS, HPLC, or other techniques known to those of ordinary skill in the art. In some cases, the concentrations of at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, or at least 50 fatty acids may be determined, e.g., in the fluid sample. It should be understood that the concentration determined need not be absolute concentrations, and may be relative (e.g., having arbitrary units) in some embodiments. In addition, in some cases, other characteristics of fatty acids, such as reactivities, may be determined, e.g., in addition to or instead of concentration.

[0046] For example, in some embodiments, a probabilistic classifier may be used to determine probabilities based on some or all of the fatty acids determined in the sample (e.g., blood or other biological fluid). Fatty acids may be determined, for example, as a presence, as a concentration, as reactivity, etc. The probabilistic classifier, in some embodiments, may compare the concentration of the unsaturated fatty acid to a model prediction to determine a cancer probability. In general, a probabilistic classifier produces a probability or correlation that the fatty acid concentration is indicative of a subject having cancer. Examples of probabilistic classifiers include, but are not limited to, Gaussian Naive Bayesian (GNB) analysis, logistic regression analysis, or the like. For example, the model may be used to predict whether a given fatty acid concentration is from an individual with the disease (e.g., cancer), or an individual without the disease.

[0047] In some embodiments, a probabilistic classifier, such as a GNB classifier, may be pretrained on the presence and / or concentration of one or more fatty acids (e.g., such as any of those described herein) for subjects having cancer (or another disease) and control subjects. The GNB model or other probabilistic classifiers can be specially tailored to work with small training data sets and still accurately return predictions or classifications on whether a subject has cancer or another disease. Various embodiments may allow accurate predictions to be returned on test data with relatively small training sample sizes. For example, the data set for training may include less than 10,000, less than 5,000 less than 1,000, less than 500, or less than 100 subjects having cancer. This is an improvement over conventional approaches that require clinically manifest cancer for data sets used for training.

[0048] In some cases, this process may be repeated for more than one fatty acid, allowing a plurality of individual probabilities to determined for the various fatty acids. These probabilities may be combined in order to determine an overall probability, e.g., of a subject having cancer or another disease. These probabilities may combined, linearly or nonlinearly, for example, using various weighting metrics, such as a Diagnostic Odds Ratio (DOR). The Diagnostic Odds Ratio for a fatty acid may be indicative of how predictive a particular fatty acid is of a subject having cancer (or another disease). Multiple models can be trained on individual fatty acids, combinations of fatty acids, and the output probabilities or classifications combined into a binary evaluation / classification, e.g., whether cancer or another disease is present or not present. A weighting function, such as a DOR, may correlate the concentration of a specific fatty acid with a disease state (for example, cancer) or a normal state, and different fatty acids may exhibit different weight functions. A weighing function of “0” may indicate that a particular fatty acid is not correlated to either a disease state of a normal state. A higher weighing function (e.g., greater than 1) may indicate a positive correlation with a disease state, while a lower weighing function (e.g., less than 1) may indicate a negative correlation with a disease state. In a negative correlation, the lower the concentration of the fatty acid, the higher the probability of cancer. Without wishing to be bound by any theory, it is believed that this may be due in some embodiments to the presence of cancer producing reactive oxygen species, which may interact with fatty acids, and thus lower the concentration.

[0049] The Diagnostic Odds Ratio may be determined as a ratio of positive results in subjects with a disease (e.g., cancer) to a ratio of positive results in subjects without the disease. For instance, in some embodiments, a DOR may be determined by using a series of test subjects having a disease, and control subjects not having the disease, and measuring a ratio of those with the disease having a positive test to those without the disease having a positive test.

[0050] Thus, in some cases, specific fatty acids may be used, e.g., fatty acids exhibiting a DOR of greater than 1, or less than 1 in some embodiments. In some cases, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more fatty acids, each having a DOR greater than 1, and / or less than 1, may be determined in a biological sample, e.g., blood, taken from a subject, and used to determine whether or not the subject has a disease (e.g., cancer).

[0051] In some embodiments, various models may be pre-trained on data specifically correlated to fatty acids and cancers (or other diseases). These models can be used alone, together, and / or in various combination to provide a classification of the presence or absence of cancer or another disease. In some embodiments, a model determination of presence of cancer can be used to generate an additive overall probability, and the overall probability used in the final classification result.

[0052] Examples of fatty acids having a DOR of greater than 1 include, but are not limited to, dodecanoic acid, lOc-pentadecenoic acid, arachidonic acid, 6t-octadecenoic acid, 11c- octadecenoic acid, linalolinic acid, nonadecanoic acid, 9t,12t-octadecadienoic acid, 11c- eicosenoic acid, 13c,16c-docosadienoic acid, and 4c,7c,10c,13c,16c,19c-docosahexanenoic acid. As mentioned, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc., of these may be determined in various embodiments.

[0053] Examples of fatty acids having a DOR of greater than 1 include, but are not limited to, tetradecanoic acid, 9t,12c-octadecadienoic acid, 9c,12c,15c-octadecatrienoic acid, linolaic acid, 5c,8c,l lc,14c,17c-eicosapentaenoic acid, 7c,10c,13c,16c-docosatetraenoic acid, and 7c,10c,13c,16c,19c-docosapentaenoic acid. As mentioned, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc., of these may be determined in various embodiments.

[0054] Based on such probabilities, in certain aspects, a subject may optionally be treated for the cancer or other disease. A variety of cancer treatments are known, and include, but are not limited to, surgery, chemotherapy, radiation therapy, hormonal therapy, antibody therapy, cancer inhibitors, hyperthermia, immunotherapy, photodynamic therapy, stem-cell therapy, or the like.

[0055] As used herein, “treat” to either therapeutic treatment or prophylactic or preventative measures, wherein the object is to prevent or lessen the targeted pathologic condition or disorder as described herein (e.g., cancer). Thus, in some embodiments, treating may include directly affecting or curing, suppressing, inhibiting, preventing, reducing the severity of, delaying the onset of, reducing symptoms associated with the disease, disorder or condition, or a combination thereof. In some embodiments, “treating” refers inter alia to delaying progression, expediting remission, inducing remission, augmenting remission, speeding recovery, increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof.

[0056] Non-limiting examples of cancers that can be determined or treated include lung cancer or ovarian cancer. Other examples include, but is not limited to: biliary tract cancer; bladder cancer; brain cancer including glioblastomas and medulloblastomas; breast cancer; cervical cancer; choriocarcinoma; colon cancer; endometrial cancer; esophageal cancer; gastric cancer; hematological neoplasms including acute lymphocytic and myelogenous leukemia; multiple myeloma; AIDS-associated leukemias and adult T-cell leukemia lymphoma; intraepithelial neoplasms including Bowen’s disease and Paget’s disease; liver cancer; lung cancer; lymphomas including Hodgkin’s disease and lymphocytic lymphomas; neuroblastomas; oral cancer including squamous cell carcinoma; ovarian cancer including those arising from epithelial cells, stromal cells, germ cells and mesenchymal cells; pancreatic cancer; prostate cancer; rectal cancer; sarcomas including leiomyosarcoma, rhabdomyosarcoma, liposarcoma, fibrosarcoma, and osteosarcoma; skin cancer including melanoma, Kaposi’s sarcoma, basocellular cancer, and squamous cell cancer; testicular cancer including germinal tumors such as seminoma, non- seminoma, teratomas, choriocarcinomas; stromal tumors and germ cell tumors; thyroid cancer including thyroid adenocarcinoma and medullar carcinoma; and renal cancer including adenocarcinoma and Wilms’ tumor. Commonly encountered cancers include breast, prostate, lung, ovarian, colorectal, and brain cancer. In general, an effective amount of the one or more compositions of the invention for treating cancer will be that amount necessary to inhibit mammalian cancer cell proliferation in situ. Those of ordinary skill in the art are well-schooled in the art of evaluating effective amounts of anti-cancer agents.

[0057] Other examples of diseases that involve changes in reactive oxygen species include, but are not limited to, diseases such as airway inflammation, Acute Respiratory Distress Syndrome (ARDS), aging, asthmas, emphysema, rheumatoid arthritis, atherosclerosis, alcohol addition, certain types of cardiovascular disease, certain types of chronic inflammatory diseases, or certain types of neurodegenerative diseases, such as Lou Gehrig’s Disease, Parkinson’s Disease, Alzheimer’s Disease, sporadic amytrophic lateral sclerosis, or Huntington’s Disease. Such diseases often may be characterized by chronic altered metabolic states in which there are elevated concentrations of certain reactive oxygen species. In some embodiments, higher reactive oxygen species may be caused by inflammation.

[0058] In some aspects, a composition may additionally comprise one or more adjunct ingredients. For example, a composition may include additional ingredients such as salts, buffering agents, diluents, excipients, chelating agents, fillers, drying agents, antioxidants, antimicrobials, preservatives, binding agents, bulking agents, silicas, solubilizers, or stabilizers. Non-limiting examples include species such as calcium carbonate, sodium carbonate, lactose, kaolin, calcium phosphate, or sodium phosphate; granulating and disintegrating agents such as com starch or algenic acid; binding agents such as starch, gelatin or acacia; lubricating agents such as magnesium stearate, stearic acid, or talc; timedelay materials such as glycerol monostearate or glycerol distearate; suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone; dispersing or wetting agents such as lecithin or other naturally-occurring phosphatides; thickening agents such as cetyl alcohol or beeswax; buffering agents such as acetic acid and salts thereof, citric acid and salts thereof, boric acid and salts thereof, or phosphoric acid and salts thereof; or preservatives such as benzalkonium chloride, chlorobutanol, parabens, or thimerosal. Suitable concentrations can be determined by those of ordinary skill in the art, using no more than routine experimentation. Those of ordinary skill in the art will know of other suitable formulation ingredients, or will be able to ascertain such, using only routine experimentation. Preparations can include sterile aqueous or nonaqueous solutions, suspensions and emulsions, which can be isotonic with the blood of the subject in certain embodiments. Examples of nonaqueous solvents are polypropylene glycol, polyethylene glycol, vegetable oil such as olive oil, sesame oil, coconut oil, arachis oil, peanut oil, mineral oil, organic esters such as ethyl oleate, or fixed oils including synthetic mono or di-glycerides. Aqueous solvents include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, 1,3- butandiol, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, antioxidants, chelating agents and inert gases and the like. Those of skill in the art can readily determine the various parameters for preparing and formulating the compositions of the invention without resort to undue experimentation .

[0059] Additionally, an illustrative implementation of a special purpose computer system 300 that may be specially programmed to be used in connection with any of the embodiments of the disclosure provided herein is shown in Fig. 3. The computer system 300 may include one or more processors 310 and one or more articles of manufacture that comprise non-transitory computer-readable storage media (e.g., memory 320 and one or more non-volatile storage media 330). The processor 310 may control writing data to and reading data from the memory 320 and the non-volatile storage device 330 in any suitable manner. To perform any of the functionality described herein (e.g., build predictive models, provide inputs to the predictive models, and return probabilistic outputs indicating presence of cancer / cancer cells, select pre-trained models based on a respective input, combine outputs from pre-trained models to generate a combined probability of cancer presence, construct combined models for various fatty acid metrics and / or combinations of specific fatty acids measurements, return a single output probability for combined fatty acid metric inputs from the combined predictive model (e.g., pre-trained on a plurality of fatty acid targets, various combinations of the fatty acid targets, etc.), among other options), the processor 310 may execute one or more processor-executable instructions stored in one or more non-transitory computer-readable storage media (e.g., the memory 320), which may serve as non-transitory computer-readable storage media storing processor-executable instructions for execution by the processor 310. The terms “program” or “software” or “app” are used herein in a generic sense to refer to any type of computer code or set of processor-executable instructions that can be employed to program a computer or other processor to implement various aspects of embodiments as discussed above. Additionally, it should be appreciated that according to one aspect, one or more computer programs that when executed perform methods of the disclosure provided herein need not reside on a single computer or processor, but may be distributed in a modular fashion among different computers or processors to implement various aspects of the disclosure provided herein.

[0060] Processor-executable instructions may be in many forms, such as program modules, executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically, the functionality of the program modules may be combined or distributed as desired in various embodiments.

[0061] Also, data structures may be stored in one or more non-transitory computer-readable storage media in any suitable form. For simplicity of illustration, data structures may be shown to have fields that are related through location in the data structure. Such relationships may likewise be achieved by assigning storage for the fields with locations in a non-transitory computer-readable medium that convey relationships between the fields. However, any suitable mechanism may be used to establish relationships among information in fields of a data structure, including through the use of pointers, tags or other mechanisms that establish relationships among data elements.

[0062] Also, various inventive concepts may be embodied as one or more processes, of which examples have been provided. The acts performed as part of each process may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.

[0063] U.S. Provisional Patent Application Serial No. 63 / 622,467, filed January 18, 2024, entitled “Systems and Methods for Detection of Cancer Using Fatty Acids,” by Fossel, is incorporated herein by reference in its entirety.

[0064] The following examples are intended to illustrate certain embodiments of the present disclosure, but do not exemplify the full scope of the disclosure.

[0065] EXAMPLE 1 In this example, a blood sample is obtained from a subject being tested, and fatty acid analysis is carried out using an analytic method such as GC / MS. The analysis may include one or more fatty acids (for example, 48 fatty acids, or other numbers such as those described herein).

[0066] An analytical technique, such as Gaussian Naive Bayesian analysis, can be used to determine individual probabilities of cancer for some or all of the fatty acids. See, e.g., Fig. 1 for an example of Gaussian Naive Bayesian analysis. One example methodology to produce a suitable training model for such analysis is shown in Fig. 2

[0067] These may be combined in some cases, resulting in an overall probability of cancer in the subject based on the blood sample. For example, a Diagnostic Odds Ratio (DOR) for each individual fatty acid may be determined, and fatty acids with DOR greater than one are included in the subsequent analysis. The DOR is the ratio of those with disease having a positive test to those without disease having a positive test. This is shown schematically in Fig. 3.

[0068] To explore the contribution of individual fatty acids to overall model performance, models such as Gaussian Naive Bayesian analysis may be used, with only one fatty acid as an input. In some cases, this may reduce the model to just 2 Gaussians, e.g., one for cancer subjects and one for control subjects.

[0069] EXAMPLE 2

[0070] This example illustrates various experiments in which lung cancer subjects versus control subjects, and ovarian cancer subjects versus control subjects, were performed. Fig. 4 shows the results of these studies.

[0071] This example illustrates the prediction of cancers in accordance with one embodiment. A large panel of -80,000 female subjects had their blood drawn, persevered using EDTA, and frozen. After 1-2 years, those subjects that developed lung cancer (nonsmall cell lung cancer) or ovarian cancer were selected for analysis, and matched with similarly-aged subjects that did not develop cancer. Approximately 25 test subjects were identified and matched against control subjects.

[0072] The blood of the test and control groups was analyzed for fatty acids. Fatty acids were determined using HPLC. Concentrations of the following unsaturated fatty acids were determined for each sample: 9c-tetradecenoic acid, 10c -pentadecenoic acid, 9c-hexadecenoic acid, 9c-octadecenoic acid, l lc-octadecenoic acid, l lc-eicosenoic acid, 15c-tetrasenoic acid, 9c,12c,15c-octadecatrienoic acid, 5c,8c,l lc,14cl7c-eicosapentaenoic acid, 7c,10c,13c,16c,19c-docosapentaenoic acid, 4c,7c,10c,13c,16c,19c-docosahexaenoic acid, 9c,12c-octadecadienoic acid, 6c,9c,12c-octadecatrienoic acid, l lc,14c-eicosadienoic acid, 8c,l lc,14c-eicosatrienoic acid, 5c,8c,l l lc,14c-eicosatetraenoic acid, 13c,16c-docosadienoic acid, 7c,10c,13c,16c-docosatetraenoic acid, 9t-tetadecenoic acid, 9t-hexadecenoic acid, 6t- octadecenoic acid, 9t-octadecenoic acid, l lt-octadecenoic acid, 9t,12t-octadecadienoic acid, 9c,12t-octadecadienoic acid, 9t,12c-octadecadienoic acid, l lt-eicosenoic acid, and 9c,l lt- octadecadienoic acid. Each fatty acid was then compared for the control and test groups using Gaussian Naive Bayesian analysis to produce a Diagnostic Odds Ratio (DOR) to determine a probability of cancer based on each fatty acid.

[0073] It was found that the fatty acids with the highest DOR’s were dodecanoic acid, 10c- pentadecenoic acid, arachadonic acid, 6t-octadecenoic acid, l lc-octadecenoic acid, linalolinc acid, nonadecanoic acid, 9t,12t-octadecenoic acid, l lc-eicosenoic acid, 13c, 16c- docosadienoic acid, and 4c,7c,10c,13c,16c,19c-docosahexaenoic acid. The fatty acids with the lowest DOR’s were tetradecanoic acid, 9t,12c-octadecadienoic acid, 9c, 12c, 15c- octadecatrienoic acid, linolaic acid, 5c,8c,l lc,14cl7c-eicosapentaenoic acid, 7c, 10c, 13c, 16c- docosatetraenoic acid, and 7c,10c,13c,16c,19c-docosapentaenoic acid. These are shown in Fig. 5 with different DOR values, with the abbreviations shown in Fig. 6.

[0074] While several embodiments of the present disclosure have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present disclosure. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present disclosure is / are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the disclosure described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the disclosure may be practiced otherwise than as specifically described and claimed. The present disclosure is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present disclosure.

[0075] In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, then the document having the later effective date shall control.

[0076] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0077] The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.”

[0078] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0079] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”

[0080] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0081] When the word “about” is used herein in reference to a number, it should be understood that still another embodiment of the disclosure includes that number not modified by the presence of the word “about.”

[0082] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0083] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

What is claimed is:CLAIMS1. A method of treating a subject suspected of having cancer, comprising: administering a plurality of fatty acids to a subject; withdrawing blood from the subject; determining a concentration of each of the plurality of fatty acids in the blood; for each of the plurality of unsaturated fatty acids, determining a cancer probability to the unsaturated fatty acid using a probabilistic classifier; and treating the subject for cancer based on the cancer probabilities.

2. The method of claim 1, wherein the fatty acids are unsaturated.

3. The method of any one of claims 1 or 2, comprising determining the concentration using GC / MS.

4. The method of any one of claims 1-3, comprising determining the concentration using HPLC.

5. The method of any one of claims 1-4, wherein the probabilistic classifier comprises Gaussian Naive Bayesian analysis.

6. The method of any one of claims 1-5, wherein the probabilistic classifier comprises comparing the concentration of the fatty acid to a model prediction to determine a cancer probability.

7. The method of any one of claims 1-6, wherein the probabilistic classifier comprises logistic regression analysis.

8. The method of any one of claims 1-7, wherein the probabilistic classifier is pretrained on fatty concentration and positive cancer samples.

9. The method of any one of claims 1-8, comprising determining a concentration of at least 10 fatty acids in the blood.

10. The method of any one of claims 1-9, comprising determining a concentration of at least 20 fatty acids in the blood.

11. The method of any one of claims 1-10, comprising determining a concentration of at least 40 fatty acids in the blood.

12. The method of any one of claims 1-11, wherein the subject suspected of having lung cancer.

13. The method of any one of claims 1-12, wherein the subject suspected of having ovarian cancer.

14. The method of any one of claims 1-13, comprising orally administering the plurality of fatty acids to the subject.

15. The method of any one of claims 1-14, comprising injecting the plurality of fatty acids into the subject.

16. The method of any one of claims 1-15, wherein the plurality of fatty acids includes one or more of linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9,11- octadecadienoic acid, or 10,12-octadecadienoic acid.

17. The method of any one of claims 1-16, wherein the plurality of fatty acids includes one or more of octanoic acid, decanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, docosanoic acid, tricosanoic acid, tetracosanoic acid, 9c-tetradecenoic acid, lOc-pentadecenoic acid, 9c- hexadecenoic acid, 9c-octadecenoic acid, llc-octadecenoic acid, llc-eicosenoic acid, 15c-tetrasenoic acid, 9c,12c,15c-octadecatrienoic acid, 5c,8c,llc,14cl7c-eicosapentaenoic acid, 7c,10c,13c,16c,19c-docosapentaenoic acid, 4c,7c,10c,13c,16c,19c-docosahexaenoic acid, 9c,12c-octadecadienoic acid, 6c, 9c, 12c- octadecatrienoic acid, llc,14c-eicosadienoic acid, 8c,llc,14c-eicosatrienoic acid, 5c,8c,lllc,14c-eicosatetraenoic acid, 13c,16c-docosadienoic acid, 7c, 10c, 13c, 16c- docosatetraenoic acid, 9t-tetadecenoic acid, 9t-hexadecenoic acid, 6t-octadecenoic acid, 9t-octadecenoic acid, llt-octadecenoic acid, 9t,12t-octadecadienoic acid, 9c,12t- octadecadienoic acid, 9t,12c-octadecadienoic acid, llt-eicosenoic acid, or 9c,llt- octadecadienoic acid.

18. The method of any one of claims 1-17, wherein the plurality of fatty acids includes one or more of dodecanoic acid, lOc-pentadecenoic acid, arachidonic acid, 6t- octadecenoic acid, l lc-octadecenoic acid, linalolinic acid, nonadecanoic acid, 9t,12t- octadecadienoic acid, l lc-eicosenoic acid, 13c,16c-docosadienoic acid, and 4c,7c,10c,13c,16c,19c-docos ahexanenoic acid.

19. The method of any one of claims 1-18, wherein the plurality of fatty acids includes one or more of tetradecanoic acid, 9t,12c-octadecadienoic acid, 9c, 12c, 15c- octadecatrienoic acid, linolaic acid, 5c,8c,l lc,14c,17c-eicosapentaenoic acid, 7c,10c,13c,16c-docosatetraenoic acid, and 7c,10c,13c,16c,19c-docosapentaenoic acid.

20. A composition, comprising: a liquid comprising at least 10 fatty acids, each at a concentration of at least 10 mmol / L, including the fatty acids linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9, 11 -octadecadienoic acid, and 10,12-octadecadienoic acid.

21. The composition of claim 20, wherein the fatty acids are saturated.

22. The composition of any one of claims 20 or 21, wherein the liquid is an aqueous solution.

23. The composition of any one of claims 20-22, wherein the liquid comprises blood.

24. The composition of any one of claims 20-23, wherein the plurality of unsaturated fatty acids includes one or more of linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9, 11 -octadecadienoic acid, or 10,12-octadecadienoic acid.

25. The composition of any one of claims 20-24, wherein the plurality of unsaturated fatty acids includes one or more of octanoic acid, decanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, docosanoic acid, tricosanoic acid, tetracosanoic acid, 9c-tetradecenoic acid, 10c- pentadecenoic acid, 9c-hexadecenoic acid, 9c-octadecenoic acid, llc-octadecenoic acid, llc-eicosenoic acid, 15c-tetrasenoic acid, 9c,12c,15c-octadecatrienoic acid, 5c,8c,llc,14cl7c-eicosapentaenoic acid, 7c,10c,13c,16c,19c-docosapentaenoic acid, 4c,7c,10c,13c,16c,19c-docosahexaenoic acid, 9c,12c-octadecadienoic acid, 6c, 9c, 12c- octadecatrienoic acid, llc,14c-eicosadienoic acid, 8c,llc,14c-eicosatrienoic acid, 5c,8c,lllc,14c-eicosatetraenoic acid, 13c,16c-docosadienoic acid, 7c, 10c, 13c, 16c- docosatetraenoic acid, 9t-tetadecenoic acid, 9t-hexadecenoic acid, 6t-octadecenoic acid, 9t-octadecenoic acid, llt-octadecenoic acid, 9t,12t-octadecadienoic acid, 9c,12t- octadecadienoic acid, 9t,12c-octadecadienoic acid, llt-eicosenoic acid, or 9c,llt- octadecadienoic acid.

26. The composition of any one of claims 20-25, wherein the plurality of fatty acids includes one or more of dodecanoic acid, 10c -pentadecenoic acid, arachidonic acid, 6t-octadecenoic acid, l lc-octadecenoic acid, linalolinic acid, nonadecanoic acid, 9t,12t-octadecadienoic acid, l lc-eicosenoic acid, 13c,16c-docosadienoic acid, and 4c,7c,10c,13c,16c,19c-docos ahexanenoic acid.

27. The composition of any one of claims 20-26, wherein the plurality of fatty acids includes one or more of tetradecanoic acid, 9t,12c-octadecadienoic acid, 9c, 12c, 15c- octadecatrienoic acid, linolaic acid, 5c,8c,l lc,14c,17c-eicosapentaenoic acid, 7c,10c,13c,16c-docosatetraenoic acid, and 7c,10c,13c,16c,19c-docosapentaenoic acid.

28. A composition, comprising: a liquid comprising at least 10 unsaturated fatty acids, each unsaturated fatty acid having a mass of at least 1 g, including the fatty acids linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9, 11 -octadecadienoic acid, and 10,12- octadecadienoic acid.

29. The composition of claim 28, wherein the fatty acids are saturated.

30. The composition of any one of claims 28 or 29, wherein the plurality of unsaturated fatty acids includes one or more of linoleic acid, linolenic acid, arachidonic acid, oleic acid, 9, 11 -octadecadienoic acid, or 10,12-octadecadienoic acid.

31. The composition of any one of claims 28-30, wherein the plurality of unsaturated fatty acids includes one or more of octanoic acid, decanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, docosanoic acid, tricosanoic acid, tetracosanoic acid, 9c-tetradecenoic acid, 10c- pentadecenoic acid, 9c-hexadecenoic acid, 9c-octadecenoic acid, llc-octadecenoic acid, llc-eicosenoic acid, 15c-tetrasenoic acid, 9c,12c,15c-octadecatrienoic acid, 5c,8c,llc,14cl7c-eicosapentaenoic acid, 7c,10c,13c,16c,19c-docosapentaenoic acid, 4c,7c,10c,13c,16c,19c-docosahexaenoic acid, 9c,12c-octadecadienoic acid, 6c, 9c, 12c- octadecatrienoic acid, llc,14c-eicosadienoic acid, 8c,llc,14c-eicosatrienoic acid, 5c,8c,lllc,14c-eicosatetraenoic acid, 13c,16c-docosadienoic acid, 7c, 10c, 13c, 16c- docosatetraenoic acid, 9t-tetadecenoic acid, 9t-hexadecenoic acid, 6t-octadecenoic acid, 9t-octadecenoic acid, llt-octadecenoic acid, 9t,12t-octadecadienoic acid, 9c,12t- octadecadienoic acid, 9t,12c-octadecadienoic acid, llt-eicosenoic acid, or 9c,llt- octadecadienoic acid.

32. The composition of any one of claims 28-31, wherein the plurality of fatty acids includes one or more of dodecanoic acid, 10c -pentadecenoic acid, arachidonic acid, 6t-octadecenoic acid, l lc-octadecenoic acid, linalolinic acid, nonadecanoic acid,9t,12t-octadecadienoic acid, l lc-eicosenoic acid, 13c,16c-docosadienoic acid, and 4c,7c,10c,13c,16c,19c-docos ahexanenoic acid.

33. The composition of any one of claims 28-32, wherein the plurality of fatty acids includes one or more of tetradecanoic acid, 9t,12c-octadecadienoic acid, 9c, 12c, 15c- octadecatrienoic acid, linolaic acid, 5c,8c,l lc,14c,17c-eicosapentaenoic acid, 7c,10c,13c,16c-docosatetraenoic acid, and 7c,10c,13c,16c,19c-docosapentaenoic acid.

34. The composition of any one of claims 28-33, wherein the composition comprises a pharmaceutically acceptable carrier.

35. A method of treating a subject suspected of having cancer, comprising: determining a concentration of each of a plurality of fatty acids in the blood; for each of the plurality of unsaturated fatty acids, determining a cancer probability to the unsaturated fatty acid using a probabilistic classifier; and treating the subject for cancer based on the cancer probabilities.

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