Disclosed herein, inter alia, are methods and compositions for detecting a plurality of nucleic acids in a sample.

A method for constructing a library of cell-free DNAs in body fluids, comprising directly acting a transposase or an endonuclease on a body fluid sample, fragmenting the cell-free DNAs within, and performing amplification to obtain a library. Also provided is a test kit using the present method for prenatal diagnosis or early detection of cancer.

Provided herein are compositions and methods for the incorporation of unnatural nucleotides using mutant polymerases, such as reverse transcriptases. Further provided herein are methods of detection and sequencing of polynucleotide sequences. In some aspects, the compositions and methods are used enhance the efficiency and speed of detecting nucleotide bases. The methods and compositions described herein may further reduce time, cost, or scale of devices for next generation sequencing platforms.

Provided herein are methods and composition for processing samples that contain nucleic acids, or cells containing nucleic acids, of a microbiome, using amounts of primers within a range of mole values and rounds of polymerase chain reaction (PCR) within a range of numbers of rounds.

Provided herein are compositions, devices, systems and methods for generation and use of biomolecule-based information for storage. Further provided are devices-having addressable electrodes controlling polynucleotide synthesis (deprotection, extension, or cleavage, etc.) The compositions, devices, systems and methods described herein provide improved storage, density, and retrieval of biomolecule-based information.

Provided is a method for amplifying a nucleic acid from RNA with high sensitivity and a high yield. The method for amplifying a nucleic acid comprises: synthesizing cDNA from sample RNA through reverse transcription reaction; and amplifying the cDNA by multiplex PCR, wherein the reverse transcription and the multiplex PCR are performed in the presence of a single-stranded nucleic acid-binding protein, and the single-stranded nucleic acid-binding protein is T4GP32 or a mutant thereof.

The present invention provides methods for large-scale production of a composition enriched for full-length mRNA molecules using an SP6 RNA polymerase and compositions produced using such methods and uses thereof.

Provided herein are various methods for enriching a target fragment that is present in randomly sheared genomic DNA. In some embodiments, the method may involve hybridizing randomly sheared genomic DNA to a halo probe to produce a first circular complex, and then enzymatically digesting the overhanging ends of the genomic fragment. Other embodiments may include hybridizing randomly sheared genomic DNA to an RNA oligonucleotide that comprises a region that hybridizes to a fragment of the randomly sheared genomic DNA to produce an RNA/DNA duplex. The overhanging ends of the genomic fragment in the RNA/DNA duplex can then be enzymatically digested.

A nucleic acid patch method for amplifying target nucleic acid sequences in circulating free DNA or residual DNA samples where the defining ends of the target nucleic acid sequences are unknown.

The invention combines the advantages of split and mix synthesis with the advantages of template directed synthesis. The method comprises the steps of: a) adding a linker molecule L to one or more reaction wells; b) adding a molecule fragment to each of said reaction wells; c) adding an oligonucleotide identifier to each of said reaction wells; d) subjecting said wells to conditions sufficient to allow said molecule fragments and said oligonucleotide identifiers to become attached to said linker molecule, or conditions sufficient for said molecule fragments to bind to other molecule fragments and sufficient for said oligonucleotide identifiers to bind to other oligonucleotide identifiers; e) combining the contents of said one or more reaction wells; and f) contacting the resulting bifunctional molecule(s) of step e) with one or more (oligonucleotide) templates each capable of hybridizing to at least one of the oligonucleotide identifiers added in step c).