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.

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.

Compositions and methods are provided for peptide sequences that are ligands for a T cell receptor (TCR) of interest, in a given MHC context.

Disclosed herein is a method of generating a combinatorial library of products having a diverse array of properties. In particular, the method comprises: (a) selecting one or more pairs of reactants comprising complementary functional groups; (b) mapping all possible bond arrangements between the complementary functional groups of each pair to provide a library of possible products; (c) analyzing one or more properties of each possible product to select one or more products with desired properties (desired products); and (d) synthesizing the one or more desired products. Further disclosed herein is a method that involves the retrosynthetic reduction of a complex molecule into simple starting materials.

Methods of producing compounds and combinatorial compound libraries, the compounds and libraries produced via the methods are provided, and methods of using the libraries to identify compounds having a desired property, such as a desired biological activity and the compounds identified using these methods are provided.

Methods of producing compounds and combinatorial compound libraries, the compounds and libraries produced via the methods are provided, and methods of using the libraries to identify compounds having a desired property, such as a desired biological activity and the compounds identified using these methods are provided.

This invention relates to the synthesis of nucleic acid-encoded chemical libraries using common adaptor sequences. Nucleic acid strands coupled to chemical moieties may be contacted with identifier oligonucleotides comprising coding sequences encoding the chemical moieties and an adaptor oligonucleotides, such that the adaptor oligonucleotide hybridizes to both the nucleic acid strands and the identifier oligonucleotides to allow ligation of the identifier oligonucleotides to the nucleic acid strands. The adaptor oligonucleotide is then removed. Nucleic acid-encoded chemical libraries, and methods of producing or screening such libraries are provided.

This invention relates to the synthesis of nucleic acid-encoded chemical libraries using common adaptor sequences. Nucleic acid strands coupled to chemical moieties may be contacted with identifier oligonucleotides comprising coding sequences encoding the chemical moieties and an adaptor oligonucleotides, such that the adaptor oligonucleotide hybridizes to both the nucleic acid strands and the identifier oligonucleotides to allow ligation of the identifier oligonucleotides to the nucleic acid strands. The adaptor oligonucleotide is then removed. Nucleic acid-encoded chemical libraries, and methods of producing or screening such libraries are provided.

Disclosed are a method for providing a DNA-encoding library, the DNA-encoding library and a method of decoding a DNA-encoded library. Many different DNA molecules are synthesized which differ from each other in DNA barcode sequences. Each DNA molecule is bonded to a specific substance forming different DNA-substance conjugates. The DNA-encoded library has the advantage that, for example after an enrichment experiment performed with the library, the library may be decoded in a faster and less expensive manner than known DNA-encoded libraries.

Disclosed are a method for providing a DNA-encoding library, the DNA-encoding library and a method of decoding a DNA-encoded library. Many different DNA molecules are synthesized which differ from each other in DNA barcode sequences. Each DNA molecule is bonded to a specific substance forming different DNA-substance conjugates. The DNA-encoded library has the advantage that, for example after an enrichment experiment performed with the library, the library may be decoded in a faster and less expensive manner than known DNA-encoded libraries.