191 results about "Base pair" patented technology

The invention discloses a divalent nucleic acid aptamer fluorescence detection method based on an exonuclease I auxiliary target circulation strategy, and belongs to the field of analysis and detection.The divalent nucleic acid aptamer is a repetitive sequence composed of two monovalent nucleic acid aptamers and can form double-stranded DNA through base complementary pairing with complementary strand cDNA of the divalent nucleic acid aptamer, and the divalent nucleic acid aptamer can be used for fluorescence detection of the divalent nucleic acid aptamer. The method comprises the following steps: taking a bivalent nucleic acid aptamer as a template, forming a DNA silver nanocluster (DNA-AgNCs) under the action of silver nitrate and sodium borohydride, and when the target okadaic acid exists, combining the bivalent nucleic acid aptamer with the target, so that cDNA can be replaced from double-stranded DNA by the target. Exonuclease I is added to perform enzyme digestion on the cDNA and the divalent nucleic acid aptamer, so that the fluorescence intensity of the DNA-AgNCs can be rapidly reduced. The content of the okadaic acid can be judged by detecting the change of the fluorescence intensity. The invention provides a simple, convenient, rapid, high-sensitivity and high-specificity detection method for okadaic acid detection based on a divalent nucleic acid aptamer for the first time.

The invention provides a compound for releasing a urine fluorescent biomarker under induction of mitochondrial DNA mutation as well as a preparation method and application of the compound, and belongs to the technical field of medicines. The compound disclosed by the invention is prepared by the following steps: complementarily pairing a hybrid nucleic acid nano-carrier containing single-stranded DNA (Deoxyribose Nucleic Acid), an annular fluorescent reporter molecule and a Cas12a / crRNA compound through bases of DNA or RNA, and then coating polyethyleneimine and hyaluronic acid. A CRISPR / Cas12a system is selected as a converter of tumor specific mitochondrial DNA mutation information and urine fluorescence signals, a nano delivery system which responds to mtDNA single base mutation and is used for tumor progress monitoring and early metastasis warning is designed and synthesized, and the nano delivery system has a good application prospect in tumor progress monitoring and early metastasis sensitive detection.

The present application relates to the technical field of bioinformatics, and particularly relates to a method for constructing a biological age prediction model based on DNA methylation. The method comprises the following steps: obtaining whole genome methylation sequencing data of a human peripheral blood sample; classifying cell subpopulations of the human peripheral blood sample, and performing single-cell RNA sequencing processing on each cell subpopulation to obtain single-cell sequencing data including lymphocytes, neutrophils and monocytes; performing tissue-specific analysis on CpG sites within a range of 2000 base pairs upstream and downstream of each cell subpopulation-specific transcription factor binding site according to the single-cell sequencing data and the whole genome methylation sequencing data to obtain candidate marker site data. The present application can provide strong support for early detection of accelerated aging, prediction of related disease risks and guidance of precision medicine.

The invention relates to the technical field of DNA intercalating agents, in particular to a near-infrared luminous ruthenium (II) complex, a preparation method thereof and application of the complex as a DNA intercalating agent. The preparation method comprises the following steps: firstly, preparing a precursor 4 '-(1H-benzimidazole-2-yl)-2, 2': 6 ', 2' '-terpyridyl; then, preparing a target precursor, namely, 2-(4-(anthracene-10-yl)-6-(pyrazine-2-yl) pyridine-2-yl) pyrazine as a ligand; and finally, synthesizing a complex [Ru (An-di (2-Pz) Py) (Bitpy)]. The complex is inserted into a DNA base pair as an intercalating agent, has very strong interaction with DNA, and provides basic research for researching the interaction mode of the ruthenium (II) polypyridine complex of the tridentate ligand and DNA and taking the ruthenium (II) polypyridine complex as a diagnosis and treatment reagent.

This invention discloses a G4-DNA tetrahedral probe electrode, its preparation method, applications, and application methods. This invention utilizes four DNA strands to self-assemble into a DNA tetrahedral structure based on Watson-Crick hybridization. The DNA tetrahedron and G4 strand can be connected to the electrode based on the interaction between thiol groups and the gold electrode, and complementary base pairing. The addition of the DNA tetrahedron, through the construction of a reasonable probe density, further improves the detection sensitivity. This invention utilizes square wave voltammetry for electrochemical detection of malachite green. The content of malachite green can be determined based on the strength of the current signal of its characteristic peak. Rapid detection of malachite green can be achieved in a short time, with a minimum detection concentration of 3.65 μg / kg, showing potential for on-site detection. Six repeated tests using this electrode yielded almost identical detection signals, indicating that the electrode has good reusability and stability.

To provide a chimeric ligase having improved discrimination ability to a mismatched base pair.SOLUTION: The present invention provides a chimeric ligase, wherein an OB-fold domain or an adenylation domain in a ligase derived from a thermophilic bacterium is substituted with a corresponding domain of a different species derived from a thermophilic bacterium, and the ability to discriminate a mismatched base pair is improved as compared with the ligase before substitution.SELECTED DRAWING: None

The invention provides a DNA frame confinement probe, a preparation method thereof and application of the DNA frame confinement probe in drawing micromolecular mercaptan fluctuation in endolysosome. The probe comprises a frame and a functional component, the functional component comprises a small molecule mercaptan response unit and a fluorescent unit, and the functional component is connected to the frame. The framework is of a regular tetrahedral structure and is formed by an S1-8th chain, an S2 chain, an S3 chain and an S4 chain through base complementary pairing and self-assembly. The small molecule thiol response unit is a fluorescent probe CyS2 and is coupled with the S1-8th chain through a copper-free click chemical reaction. The fluorescent unit is marked at the 3'end of the S2 chain by Alexa Fluor 488 fluorescent molecules. The DNA frame confinement probe is accurate and stable in targeting, outstanding in anti-interference capability, high in clinical applicability and high in detection specificity.

Methods and systems are provided that include measuring the size of a plurality of nucleic acid molecules using multiplex digital amplification reactions. In various embodiments, a digital amplification reaction uses multiple separate forward and reverse primer pairs to amplify targeted regions of the nucleic acid molecule, where the targeted regions are separated by a specified number of base pairs. In other embodiments, the digital amplification reaction uses a plurality of primer pairs that share a universal pair to amplify target regions that overlap each other. The methods and systems are particularly useful for determining the size distribution of nucleic acid molecules, or classifying the pathology of a subject from which nucleic acid molecules are sampled. Advantageously, the methods and systems can measure the size of long nucleic acid molecules without relying on inefficient amplification of very long amplicons.

The application discloses a kind of preparation and application of multi-target small nucleic acid drug based on small activation RNA technology, and is related to the field of biotechnology.The preparation method of the multi-target small nucleic acid drug includes the following steps: (1) selecting at least two anti-disease genes according to target disease;(2) intercepting the sequence of 1000 base pairs of the promoter region upstream of the coding region of the anti-disease gene;(3) according to the promoter sequence, avoid CpG island and locate the segment of species conservation, and cut a sequence containing 19 base length as a sense strand;(4) design an antisense strand according to the sense strand, and the 19 base of the antisense strand and the sense strand are completely complementary;(5) add two deoxythymine or uracil to the 3' end of each chain.The multi-target small nucleic acid drug has good therapeutic effect on heart failure, and has strong cancer cell killing ability and inhibition ability of cancer cell migration, and has wide application prospect.

Methods are provided for detecting gene deletions and driver mutations using tumor-specific methylation patterns from cell-free DNA and tissue biopsies. The methods exploit the mutual exclusivity between tumor-specific methylation and homozygous gene deletion, enabling detection through absence of expected methylation signals. Applications include detection of MTAP, PTEN, and RB1 deletions, as well as prediction of EGFR single nucleotide (SNV) and small (up to 50 base pair) insertions and deletions (indel) driver mutations, enabling identification of patients eligible for targeted therapies.

This invention relates to the interdisciplinary field of smart healthcare and digital twin technology, specifically to a dynamic medical twin system and interactive prediction method based on a physiological double helix driven and four-dimensional linkage modalities. The system continuously collects and fuses multi-source biophysical data through a physical entity helix, while a digital virtual helix solves a network of physiological equations coupled with metabolic and stress fields in real time. Both systems achieve endogenous synchronous mapping of gene loci and expressed proteins through a built-in base pairing engine. The four modalities of mirroring, deduction, intervention, and knowledge are responsible for high-fidelity real-time presentation, disease progression prediction, virtual intervention deduction, and clinical knowledge accumulation, respectively, forming a complete closed loop of "observation-deduction-intervention-learning." This invention elevates the system architecture from a static hierarchical stack to a dynamic life-body metaphor, supporting users to perform virtual operations on the twin and receive real-time feedback on multi-scale physiological responses across the entire system, achieving a leap from "morphological simulation" to "life mechanism simulation."

This invention provides a multivalent protein-targeting degradation system based on a programmable nucleic acid template, its preparation method, and its applications, belonging to the fields of biomedicine and molecular engineering. The system includes monovalent nucleic acid degradation units and a nucleic acid template. The monovalent degradation unit is formed by hybridization of two nucleic acid chains coupled with a target protein ligand and an E3 ubiquitin ligase ligand. The nucleic acid template has n loading sites, which assemble into multivalent nucleic acid degraders through complementary base pairing. This invention achieves precise control over the spacing and configuration of monovalent units by regulating the template spacer sequence length and topology, resulting in a spatially ordered multivalent synergistic degradation effect and significantly improving the degradation efficiency of target proteins. This system is highly modular and programmable, providing a new technological platform for the development of targeted protein degradation drugs.

Some embodiments relate to methods, systems, uses, or software for identification of structural variants (SVs) for regions of deoxynucleic acid (DNA) sequences. A device may receive, at a processor, a dataset comprising base pair data output from a sequencing by expansion process. A device may extract, at the processor, soft-clipped reads from the received dataset. A device may group, at the processor, the extracted soft-clipped reads based at least on their respective breakpoint. A device may determine, at the processor, a presence or an absence of a somatic structural variant by k-mer matching the grouped and extracted soft-clipped reads. A device may provide, at the processor, at least one determined somatic structural variant responsive to determining the presence of the somatic structural variant

The invention relates to the technical field of biological medicines, and particularly provides a hair follicle regeneration nano activator as well as a preparation method and application thereof. The activator comprises a first coupling monomer and a second coupling monomer, an oligonucleotide sequence of the first coupling monomer and an oligonucleotide sequence of the second coupling monomer are at least partially complementary and form a double-chain structure through base pairing, the first coupling monomer is formed by coupling a first polypeptide and a first ssDNA, and the second coupling monomer is formed by coupling a second polypeptide and a second ssDNA. The second coupling monomer is formed by coupling a second polypeptide and a second ssDNA; wherein the first polypeptide and the second polypeptide are both specifically targeted to beta-catenin protein. The polypeptide-DNA-polypeptide dimer has a polypeptide-DNA-polypeptide sandwich-type dimer structure, can be specifically combined with beta-catenin in stem cells, only regulates and controls a Wnt / beta-catenin pathway, does not generate non-specific influence on other pathways, and can efficiently activate a hair follicle regeneration related signal pathway and promote a hair follicle development biological process.

The invention relates to the technical field of variety cultivation and identification in molecular biology, in particular to a molecular marker, a primer and a kit for identifying a rubber tree variety 'Yunnan research 621' and application of the molecular marker, the primer and the kit. The molecular marker is positioned on 66751525-66751724 basic groups of a No.10 chromosome, and the nucleotide sequence of the molecular marker is shown as SEQ ID No.1. The invention provides a molecular marker primer and a kit for a rubber tree variety 'Yunnan research 621', the technology can specifically identify and amplify a DNA sequence of the 'Yunnan research 621' variety, realizes accurate identification of the 'Yunnan research 621' variety, is helpful for improving the accuracy of variety identification, optimizes variety selection and regional suitability evaluation, and has the advantages of high specificity, high sensitivity, high sensitivity and the like. Therefore, a scientific basis is provided for planting and breeding of rubber trees, and healthy development of the rubber industry is promoted. The molecular marker, the primer pair or the kit can be used for distinguishing and identifying rubber tree varieties' Yunnan research 621 ', Yunnan research 651 and Yunnan research 98-305, and is simple and convenient to operate and suitable for large-scale application.

Disclosed herein are improved methods and compositions of de novo synthesis of nucleic acids by cyclic extension using nucleotides that have an N-linked or O-linked scar or protecting group, and subsequent removal of the scar or protecting group. During polymerase-nucleotide conjugate-based polynucleotide synthesis or after the synthesis is completed, nucleobases having a scar from linker cleavage can be converted back into native form by removal of the scars from the nucleobases. Secondary structure formation in the nascent chain, which may inhibit extension reactions, is suppressed by the use of monomers with protected nucleobases that prevent Watson-Crick base pairing and / or other structures. After the synthesis is completed, the nucleobases can be converted back into native form by palladium-based removal of the protecting groups.

The invention discloses an InDel molecular marker for detecting black spot resistance of broccoli, a method and application, and relates to the field of molecular biology. The site is located at 56724071bp-56724089bp of a broccoli chromosome 5, and the site has insertion / deletion variation of 18bp basic groups (the nucleotide sequence is as shown in SEQ ID NO. 1). When the site has a 18bp basic group (the sequence of an amplification product is shown as SEQ ID NO.2), the broccoli is a black spot resistant plant; otherwise, the plants are black spot sensitive plants. The invention also discloses a pair of specific primers for detecting the InDel molecular marker, and the nucleotide sequences of the specific primers are respectively shown as SEQ ID NO. 4 and SEQ ID NO. 5. The InDel molecular marker can rapidly and accurately detect the black spot resistance of broccoli germplasm resources at low cost, does not need field inoculation identification, can be used for early screening of broccoli black spot resistance varieties and molecular marker-assisted breeding, significantly improves the breeding efficiency, and shortens the breeding period.

The present invention is related to the field of gene editing. In particular, the gene editing is directed toward single nucleotide base editing. For example, such single nucleotide base editing results in a conversion of a OG base pair to a T*A base pair. The high accuracy and precision of the presently disclosed single nucleotide base gene editor is accomplished by an NmeCas9 nuclease that is fused to a nucleotide deaminase protein. The compact nature of the NmeCas9 coupled with a larger number of compatible protospacer adjacent motifs provide the Cas9 fusion constructs contemplated herein to have a gene editing window that can edit sites that are not targetable by other conventional SpyCas9 base editor platforms.

The present invention relates to a recombinant nucleic acid molecule for preparing a circular RNA comprising, from the 5'end to the 3 'end: a) an internal guide sequence (IGS), b) a ribozyme, c) a first portion of an extended anticodon arm (eACA) sequence, d) a gene of interest, and e) a second portion of the eACA sequence. One nucleotide in the second part of the eACA sequence and one nucleotide in the IGS form a swinging base pair. Recombinant nucleic acid molecules, circular RNAs, and methods of making and using the circular RNAs are provided.

The present invention relates to a modified U1 snRNA configured to rescue exon skipping in a mutant ABCA4 gene. In one aspect of the invention, there is provided a modified U1 small nuclear RNA (snRNA) configured to retain exon 40 in a mature mRNA transcript of a mutant ABCA4 gene comprising a mutation that induces exon 40 skipping wherein the mutation is located between 3 base pairs upstream and 8 base pairs downstream of a donor splice site of exon 40, wherein the modification comprises replacing a portion of the single-stranded nucleotide sequence of the 5'region of the wild-type U1 snRNA with a single-stranded binding nucleotide sequence capable of hybridizing to a target sequence present on the precursor mRNA transcript of the mutant ABCA4 gene, and wherein the target sequence is located in a region between 13 base pairs upstream and 15 base pairs downstream of the donor splice site of exon 40. In another aspect, there is provided a nucleic acid construct comprising a polynucleotide sequence encoding a modified U1 snRNA as described herein.

This invention relates to recombinant nucleic acid molecules and their use in producing circular RNA. The recombinant nucleic acid molecules comprise in the 5' to 3' direction: a) an internal guide sequence (IGS), b) a ribozyme, c) a first portion of an extended anticodon arm (eACA) sequence, d) a gene of interest, and e) a second portion of the eACA sequence. The 3' nucleotide in the second portion of the eACA sequence forms a canonical base pair with a nucleotide in the IGS or does not form a base pair with a nucleotide in the IGS. Recombinant nucleic acid molecules, methods for producing circular RNA and circular RNA thus produced are provided.

The invention belongs to the technical field of gene detection, and particularly relates to a nucleic acid detection system and method based on rewriting RPA and an RPA amplification primer, the-4--1 site base sequence of the 3'end of an upstream primer in the RPA amplification primer is TTNN, and NN represents that-1 site and-2 site bases are paired with a target gene according to the Watson-Cick principle. The atypical PAM of Cas12a enzyme obtained through experiments is TTNN, and an RPA amplification primer is correspondingly designed based on the atypical PAM structure, so that the atypical PAM is artificially introduced, Cas12a protein can accurately recognize and cut a PAM-free target gene sequence, finally, PAM non-dependent nucleic acid detection is realized, the detection application range of a CRISPR technology is remarkably expanded, and the application prospect is wide. Meanwhile, the detection specificity and the detection sensitivity are high.

The subject of the invention is a computer implemented method for constructing profile of a tissue or a cell, the profile being based on pairs of adjacent epigenetically modified bases, based on epigenetic modification information derived from nucleic acid containing epigenetically modified bases-contained in a sample relating to said tissue or a cell, the method comprising the following steps: a) providing digital data on values of epigenetic modification level measurements for epigenetically modified bases contained in said nucleic acid in said sample relating to said tissue or said cell b) determining a set of pairs of adjacent epigenetically modified bases in said nucleic acid contained in said sample relating to said tissue or said cell, each pair of adjacent epigenetically modified bases consisting of two adjacent epigenetically modified bases localized within one nucleic acid molecule so as to generate a map of adjacent epigenetically modified bases containing genomic coordinates of each identified pair of adjacent epigenetically modified bases; c) compressing information on epigenetic modification level value, iteratively for each pair of adjacent epigenetically modified bases among the determined set of pairs of adjacent epigenetically modified bases, by converting two values of epigenetic modification level associated with two epigenetically modified bases in each pair, into one single numerical value, said single value representing compressed epigenetic modification information for a pair of adjacent epigenetically modified bases and being indicative of epigenetic modification status in each pair of adjacent epigenetically modified bases; d) saving genomic coordinates of adjacent epigenetically modified bases for each pair in said determined set of pairs and compressed epigenetic modification information in the form of one single numerical value for said each pair of adjacent epigenetically modified bases in said sample, so as to generate a profile based on pairs of adjacent epigenetically modified bases of said tissue or said cell.

The invention belongs to the technical field of gene engineering and crop breeding, and particularly relates to a brassica campestris ALS natural variant gene, a mutant protein and application thereof. The Brassica campestris ALS mutant gene BrALS3R is found in rapes for the first time, consists of 1959 bases, is naturally mutated and encodes rape acetolactate synthetase III (ALS3), and compared with a wild ALS3 gene, the 1074th base of the Brassica campestris ALS mutant gene BrALS3R mutates from C to A, so that the 358th amino acid of mutant protein encoded by the Brassica campestris ALS mutant gene BrALS3R mutates from aspartic acid to glutamic acid (D358E). A plant containing the BrALS3R gene has ALS herbicide resistance, so that the gene is introduced into a plant without ALS herbicide resistance by utilizing a crossbreeding or transgenosis method, and the resistance of a receptor plant to the ALS herbicide can be improved.

The present application relates to an animal or cell having a myostatin gene in which 12 base pairs of the second exon are deleted. The present application may also comprise a composition capable of manipulating the deletion of 12 base pairs of a myostatin gene to construct the animal or the cell. The present application also relates to use of the composition for increasing muscle.

The invention discloses application of a rice OsME5 gene and a molecular marker thereof in regulation and control of rice dry direct seeding seedling emergence, the nucleotide sequence of the rice OsME5 gene is as shown in SEQ ID No.1, and the coding sequence of OsME5 protein coded by the rice gene OsME5 is as shown in SEQ ID No.2; the method comprises the following steps: knocking out an OsME5 gene by adopting a CRISPR / Cas9 method, and designing a molecular marker by utilizing natural nucleotide polymorphism (SNP) of an OsME5 promoter region SEQ ID No: 3; the OsME5 has a key SNP OsME5-578G / A at 578 base pairs on the upstream of an initiation codon, the seedling emergence ability of the germplasm carrying the OsME5-578G is relatively strong when the germplasm carrying the OsME5-578G is covered with soil and the seedling emergence ability of the germplasm carrying the OsME5-578A is relatively weak when the germplasm carrying the OsME5-578G is covered with The OsME5 gene disclosed by the invention can be applied to the field of agriculture, and a candidate gene is provided for improving the seedling emergence capability of rice soil-covering dry direct seeding.

The application belongs to but is not limited to the technical field of molecular breeding, and discloses a molecular marker for rapid detection of apple fruit hardness and ripening period and application thereof. The molecular marker for rapid detection of apple fruit hardness and ripening period comprises: SNP base A / A at the 517th position of the coding region of MdNAC5 corresponds to early maturity or small hardness germplasm, and SNP base A / T or T / T corresponds to late maturity or extremely hard germplasm. The application verifies the significant SNP on the coding region of MdNAC5 through resequencing and KASP technology, SNP base A / A at the 517th position corresponds to early maturity or small hardness germplasm, and SNP base A / T or T / T corresponds to late maturity or extremely hard germplasm. The SNP site can be used to develop a molecular marker for detecting apple fruit hardness and ripening period. The method for product typing after PCR amplification by designing specific primers at the site is fast, efficient and accurate, and can effectively improve the breeding efficiency of apples and shorten the breeding process.

An object of the present invention is to provide RNA aptamers capable of binding to ASP7967 or analogs thereof. The RNA aptamer of the present invention is an RNA aptamer that binds to ASP7967 or an analog thereof, and has the sequence: -X1-L1-X2-L2-X3- (wherein X1 has the sequence Y1GY2GY3Y4Y5; L1 is a first stem-loop nucleotide sequence comprising a first stem region, a first loop region, and a second stem region, wherein the first stem region and the second stem region are two or more base pairs in length and are substantially complementary to each other; X2 is A, G, C, or U; L2 is a second stem-loop nucleotide sequence comprising a third stem region, a second loop region, and a fourth stem region, wherein the third stem region and the fourth stem region are two or more base pairs in length and are substantially complementary to each other; the first base in the third stem region is G and the last base in the fourth stem region is C; and X3 has the sequence UY6). , Y1, Y2, Y3, Y4, Y5, and Y6 are each independently A, G, C, or U), or a third stem loop region comprising the sequence: -S1-X2-L2-X3-L3-X1-S2- (wherein S1 and S2 are each independently A, G, C, or U, and S1 and S2 can form base pairs or wobble base pairs with each other, and L3 comprises a fifth stem region, a third loop region, and a sixth stem region). the fifth stem region and the sixth stem region are one or more base pairs in length and are substantially complementary to each other, and X1, X2, X3, and L2 are as defined above), or the sequence: -S3-X3-L3-X1-L1-X2-S4- (wherein S3 is C, S4 is G, and X1, X2, X3, L1, and L3 are as defined above).

The present application belongs to the field of biological sequencing technology, and discloses a MIP probe and its application in urine free DNA capture and library construction. The MIP probe includes, from 5'-3', a 5' capture arm, an F-terminal adapter containing 10nt hypoxanthine, an R-terminal adapter, and a 3' capture arm. The present method prepares a DNA library by complementary base pairing, extension, and connection of the capture arm, is compatible with DNA fragments of different lengths and single-stranded DNA, improves template utilization, and thus facilitates the detection of low-frequency mutations in urine free DNA. The present method fixes the length of the library insert fragment by controlling the span length of the chromosomal DNA to be tested between the capture arms on both sides of the probe, making the DNBSEQ platform sequencing fluorescence signal more uniform, and the data output and quality higher. The present method combines the three steps of capture, library construction, and machine library preparation, eliminating the operations such as intermediate library quality control and pre-capture drying and concentration in conventional methods, and the operation time is shorter; there is no PCR amplification during the capture and library construction process of the present method, which reduces the error accumulation due to PCR amplification, reduces background noise, and improves the sensitivity and specificity of low-frequency mutation detection.

To provide a method for analyzing the higher-order structure of a nucleic acid.SOLUTION: Detecting a peak of imino proton within a range of chemical shift values of 10.0 to 16. 0ppm in a proton nuclear magnetic resonance spectrum; Determining the types of base pairs, optionally performing principal component and clustering analyses of the circular dichroism spectra, and optionally performing circular dichroism temperature shift measurements at single wavelengths in the range of 220 to 320nm; A step of performing curve fitting using a thermodynamic equilibrium model and performing evaluation, a step of performing ultraviolet temperature change measurement at a single wave length within a range of 290 to 300nm in some cases, and a step of determining that two or more types of nucleic acid higher-order structures including a guanine quadruplex structure are formed in a case where fitting to a state model indicating equilibrium of two or more states is shown, A step of determining that a guanine quadruplex structure is not formed when no fit to any state model indicating an equilibrium of two or more states is shown.SELECTED DRAWING: None