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.

The present invention relates to a utilizing method of a nucleic acid compound containing a selectively cleavable site. Also, the present invention relates to a DNA-encoded library containing the selectively cleavable site, a composition for synthesis therefor and a method of use thereof.

The present invention relates to a utilizing method of a nucleic acid compound containing a selectively cleavable site. Also, the present invention relates to a DNA-encoded library containing the selectively cleavable site, a composition for synthesis therefor and a method of use thereof.

Methods for preparing sequencing libraries from a DNA-containing test sample, as well as methods for correcting sequencing-derived errors, are provided.

The invention provides a chemical compound comprising a chemical moiety (p) capable of performing a binding interaction with a target molecule, and an oligonucleotide (b) or functional analogue thereof. The oligonucleotide (b) or functional analogue comprises at least one self-assembly sequence (b1) capable of performing a combination reaction with at least one self-assembly sequence (b1′) of a complementary oligonucleotide or functional analogue bound to another chemical compound comprising a chemical moiety (q). In some embodiments, the chemical compound comprises a coding sequence (b1) coding for the identification of the chemical moiety (p) and further comprises at least one self-assembly moiety (m) capable of performing a combination reaction with at least one self-assembly moiety (m′) of a similar chemical compound comprising a chemical moiety (q). The invention also provides corresponding libraries of chemical compounds as well as methods of biopanning of for target molecules and of identifying such targets.

Methods for preparing sequencing libraries from a DNA-containing test sample, as well as methods for correcting sequencing-derived errors, are provided.

Methods for preparing sequencing libraries from a DNA-containing test sample, as well as methods for correcting sequencing-derived errors, are provided.

Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.

This disclosure describes compositions, methods, and systems for constructing defined variation in a contiguous functional genetic unit in association with a unique sequence identifier (“a barcode”) in a combinatorial manner.

The present invention provides a low-frequency mutation enrichment sequencing method for free target DNA in plasma, comprising plasma DNA extraction and library construction, general library TT COLD PCR amplification enrichment, probe enrichment capture, PCR and sequencing of captured products, and positive and negatice double-strand error-correction low-frequency information analysis.