This disclosure describes methods and compositions for protein and peptide sequencing.

The present disclosure provides, in some embodiments, methods and compositions for single-molecule detection.

Described is a method for screening an encoded chemical library, which library comprises a plurality of different chemical structures each releasably linked to an encoding tag, the method comprising the steps of: (a) providing said library of tagged chemical structures; (b) releasing each chemical structure from its tag to produce a plurality of free, tagless chemical structures (TCSs); (c) screening the TCSs by contacting them with a assay system under conditions whereby a spatial association between each TCS and its tag is maintained, to produce a plurality of different screened TCSs each spatially associated with its tag; and (d) identifying a screened TCS by decoding a tag that is spatially associated therewith.

Described is a method for screening an encoded chemical library, which library comprises a plurality of different chemical structures each releasably linked to an encoding tag, the method comprising the steps of: (a) providing said library of tagged chemical structures; (b) releasing each chemical structure from its tag to produce a plurality of free, tagless chemical structures (TCSs); (c) screening the TCSs by contacting them with a assay system under conditions whereby a spatial association between each TCS and its tag is maintained, to produce a plurality of different screened TCSs each spatially associated with its tag; and (d) identifying a screened TCS by decoding a tag that is spatially associated therewith.

The invention is directed to methods for synthesizing oligonucleotides directly on biomolecules or cells living or fixed. In some embodiments, template-free enzymatic synthesis is implemented under biological conditions with successive cycles of (i) enzymatic addition of a 3′-O-blocked nucleoside triphosphate and (ii) enzymatic deblocking of the incorporated nucleotide to regenerate a free 3′ hydroxyl. The invention has applications in single-cell cDNA library construction and analysis.

The invention is directed to methods for synthesizing oligonucleotides directly on biomolecules or cells living or fixed. In some embodiments, template-free enzymatic synthesis is implemented under biological conditions with successive cycles of (i) enzymatic addition of a 3′-O-blocked nucleoside triphosphate and (ii) enzymatic deblocking of the incorporated nucleotide to regenerate a free 3′ hydroxyl. The invention has applications in single-cell cDNA library construction and analysis.

The present disclosure provides shuttle vectors for editing exogenous polynucleotides in heterologous live cells, as well as automated methods, modules, and multi-module cell editing instruments and systems for performing the editing methods.

The present disclosure provides shuttle vectors for editing exogenous polynucleotides in heterologous live cells, as well as automated methods, modules, and multi-module cell editing instruments and systems for performing the editing methods.

Provided herein are encoded split pool libraries useful, inter alia, for forming highly diverse and dense arrays for screening and detection of a variety of molecules.

Provided herein are encoded split pool libraries useful, inter alia, for forming highly diverse and dense arrays for screening and detection of a variety of molecules.