Palladium-catalyzed C(sp3)—H arylation of aliphatic carboxylic acids, amides and ketones with BNA-encoded aryl iodides in water is disclosed, Furthermore, sequential C—H arylation chemistry enabled the on-DNA synthesis of structurally-diverse scaffolds containing enriched C(sp3) character, chiral centers, cyclopropane, cyclobutane, and heterocycles. That new chemistry permits preparation of a DNA—encoded library (BEL) technology that can dramatically expedite hit identification in drug discovery owing to its ability to perform protein affinity selection with millions or billions of molecules in a single experiment. The sequential functionalization of multiple C—H bonds provides an unique avenue for creating diversity and complexity from simple starting materials. The use of water as solvent, the presence of DMA, and the extremely low concentration of DMA-encoded coupling partners (0.001 M) have previously hampered the development DMA-encoded C(sp3)—H activation reactions, but many of those hurdles have now been overcome.

Disclosed herein, inter alia, are methods and compositions for sequencing a plurality of template nucleic acids.

The present invention relates to methods for producing encoded chemical entities. In particular, the oligonucleotides and methods can include encoded chemical entities having wild-type linkages formed through chemical ligation techniques. One strategy that can be utilized that simultaneously takes advantage of chemical ligation as a means to encode chemical history, while also retaining the ability of polymerases to directly recover tag sequence and association information, is to perform chemical ligation in a manner that generates wildtype phosphodiester linkages. Such methods generally utilize condensing agents such as cyanogen bromide or similar along with 5′-phosphate and 3′-hydroxyl oligonucleotides in a double-stranded or templated context. Similarly cyanogen bromide has also been shown to chemically ligate pairs of substrate oligonucleotides that are 5′-hydroxyl and 3′-phosphate. However, these methods suffer from poor efficiency making them ill-suited for use in an iterative process such as tagging DNA-en-coded libraries.

This application provides a bead with a covalently attached chemical compound and a covalently attached DNA barcode and methods for using such beads. The bead has many substantially identical copies of the chemical compound and many substantially identical copies of the DNA barcode. The compound consists of one or more chemical monomers, where the DNA barcode takes the form of barcode modules, where each module corresponds to and allows identification of a corresponding chemical monomer. The nucleic acid barcode can have a concatenated structure or an orthogonal structure. Provided are method for sequencing the bead-bound nucleic acid barcode, for cleaving the compound from the bead, and for assessing biological activity of the released compound.

The present invention provides modified single primer extension-based methods for generating an amplified library of fragments of a target gene or genome of interest from a sample of fragmented DNA, wherein the library is suitable for use in detecting, quantifying and/or sequencing the target gene or genome of interest. The present invention also provides compositions for use in such methods. In some embodiments the present invention provides methods and compositions specifically for detecting, quantifying and/or sequencing circulating tumor derived HPV DNA.

Disclosed are a method and a device for constructing an antibody complementarity determining region (CDR) library. Also disclosed are a method, a device and a computer program product for determining the occurrence frequency of member sequences of an antibody CDR library, by means of which an antibody CDR library with a specific amino acid distribution at one or more positions can be obtained.

Described herein are methods, compositions, and systems derived from uncultivated microorganisms useful for gene editing.

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.

Disclosed is a method for obtaining a bifunctional complex comprising a molecule linked to a single stranded identifier oligonucleotide, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is a) reacted at the chemical reaction site with one or more reactants, and b) reacted enzymatically at the priming site with one or more tag(s) identifying the reactant(s).

The present invention discloses a sequencing library comprising a nucleotide sequence. The sequence comprises a linker sequence and two target sequences. Two ends of the linker sequence are respectively linked to the target sequences and the two target sequences are direct repeat sequences. The present invention further discloses preparation and use of the sequencing library. The present invention overcomes the high error rate problem of current DNA sequencing technologies, especially in a way of very low coverage bias, and can be used to detect low frequency mutations in different kinds of samples.