Abstract: The present disclosure provided methods and compositions for nucleic acid sequencing. In particular, the disclosure provides for detection of multiple different nucleotides in a sample utilizing fewer detection moieties than the number of nucleotides being detected and using two imaging events per sequencing cycle.

Abstract: The invention provides compositions and methods for sequencing nucleic acids and other applications. In sequencing by synthesis, unlabeled reversible terminators are incorporated by a polymerase in each cycle, then labeled after incorporation by binding to the reversible terminator a directly or indirectly labeled antibody or other affinity reagent.

Abstract: Provided herein are compositions, methods, and kits for enriching for one or more nucleic acid sequences of interest in a sample. The methods include providing a circular ligase, one or more 5? hook probes and/or one or more 3? hook probes and contacting the sample comprising the nucleic acids with the circular ligase and one or more 5? hook probes and/or one or more 3? hook probes under conditions to allow the hook probes to selectively bind to the one or more nucleic acid sequences of interest, and under conditions to form one or more hook products, each hook product comprising the hook probes and the one or more nucleic acid sequences of interest.

Abstract: Reversibly blocked nucleoside analogues and methods of using such nucleoside analogues for sequencing of nucleic acids are provided.

Abstract: This application relates to methods and compositions used for paired-end sequencing. The method comprises providing a DNA array comprising a surface immobilized with DNA concatemers. For each of the plurality of DNA concatemers on the array, the method comprises annealing first read primers to primer binding sites on the DNA concatemer, extending at least some of the first read primers to incorporate dNTPs or dNTP analogs, thereby producing first read strands. Each of the dNTPs or dNTP analogs being incorporated is identified to produce first reads, performing controlled MDA by extending at least some of the first read strands with a polymerase having strand-displacement activity to generate a plurality of partially hybridized second strands. Second read primers are then annealed to the single-stranded branches of the plurality of second strands to generate the second reads.

Abstract: Provided are a hooked probe, a method for ligating a nucleic acid and a method for constructing a sequencing library. The hooked probe comprises a target specific area and a hooked area ligated thereto; the target specific area comprises a sequence complementarily paired with at least part of the single chain of the nucleic acid fragment to be ligated; the hooked area comprises a sequence unpaired with the nucleic acid fragment; the end of the hooked area is a ligatable end; and the ligatable end can ligate the end of the single chain of the nucleic acid fragment.

Abstract: Provided are an adaptor element in a bubble shape, a method of constructing a sequencing library with such an adapter element. The adaptor element is a hybrid formed with a long-chain nucleic acid A and a short-chain nucleic acid B. The hybrid is in the bubble shape with paired regions at two terminals and a non-paired region in the middle.

Abstract: Provided are a vesicular adaptor and a single-chain cyclic library constructed by using the adaptor. The library can be used for RNA sequencing and other sequencing platforms dependent on a single-stranded cyclic library, and has the advantage of high throughput sequencing, high accuracy and simple operations.

Abstract: Reversibly blocked nucleoside analogues and methods of using such nucleoside analogues for sequencing of nucleic acids are provided.

Abstract: Provided are an adaptor element in a bubble shape, a method of constructing a sequencing library with such an adapter element. The adaptor element is a hybrid formed with a long-chain nucleic acid A and a short-chain nucleic acid B. The hybrid is in the bubble shape with paired regions at two terminals and a non-paired region in the middle.

Abstract: The invention provides methods and kits for ordering sequence information derived from one or more target polynucleotides. In one aspect, one or more tiers or levels of fragmentation and aliquoting are generated, after which sequence information is obtained from fragments in a final level or tier. Each fragment in such final tier is from a particular aliquot, which, in turn, is from a particular aliquot of a prior tier, and so on. For every fragment of an aliquot in the final tier, the aliquots from which it was derived at every prior tier is known, or can be discerned. Thus, identical sequences from overlapping fragments from different aliquots can be distinguished and grouped as being derived from the same or different fragments from prior tiers. When the fragments in the final tier are sequenced, overlapping sequence regions of fragments in different aliquots are used to register the fragments so that non-overlapping regions are ordered.

Abstract: Random arrays of single molecules are provided for carrying out large scale analyses, particularly of biomolecules, such as genomic DNA, cDNAs, proteins, and the like. In one aspect, arrays of the invention comprise concatemers of DNA fragments that are randomly disposed on a regular array of discrete spaced apart regions, such that substantially all such regions contain no more than a single concatemer.

Abstract: The invention provides compositions and methods for sequencing nucleic acids and other applications. In sequencing by synthesis, unlabeled reversible terminators are incorporated by a polymerase in each cycle, then labeled after incorporation by binding to the reversible terminator a directly or indirectly labeled antibody or other affinity reagent.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences. In particular, the present invention provides methods and compositions for improving the efficiency of sequencing reactions by using fewer labels to distinguish between nucleotides and by detecting nucleotides at multiple detection positions in a target sequence.

Abstract: Techniques perform de novo assembly. The assembly can use labels that indicate origins of the nucleic acid molecules. For example, a representative set of labels identified from initial reads that overlap with a seed can be used. Mate pair information can be used. A sequence read that aligns to an end of a contig can lead to using the other sequence read of a mate pair, and the other sequence read can be used to determine which branch to use to extend, e.g., in an external cloud or helper contig. A kmer index can include labels indicating an origin of each of the nucleic acid molecules that include each kmer, memory addresses of the reads that correspond to each kmer in the index, and a position in each of the mate pairs that includes the kmer. Haploid seeds can also be determined using polymorphic loci identified in a population.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences. In particular, the present invention provides methods and compositions for improving the efficiency of sequencing reactions by using fewer labels to distinguish between nucleotides and by detecting nucleotides at multiple detection positions in a target sequence.

Abstract: Random arrays of single molecules are provided for carrying out large scale analyses, particularly of biomolecules, such as genomic DNA, cDNAs, proteins, and the like. In one aspect, arrays of the invention comprise concatemers of DNA fragments that are randomly disposed on a regular array of discrete spaced apart regions, such that substantially all such regions contain no more than a single concatemer.

Abstract: Provided are a vesicular adaptor and a single-chain cyclic library constructed by using the adaptor. The library can be used for RNA sequencing and other sequencing platforms dependent on a single-stranded cyclic library, and has the advantage of high throughput sequencing, high accuracy and simple operations.

Abstract: The present invention provides methods and compositions for tagging long fragments of a target nucleic acid for sequencing and analyzing the resulting sequence information in order to reduce errors and perform haplotype phasing, for example.

Abstract: Provided are a vesicular linker and a single-chain cyclic library constructed by using the linker. The library can be used for RNA sequencing and other sequencing platforms dependent on a single-stranded cyclic library, and has the advantages of high throughput sequencing, high accuracy and simple operations.