Disclosed is an encoded chemical library microbead, which microbead has immobilized thereon and/or therein: (i) an encoding tag; and (ii) a target assay system reporter moiety, wherein the reporter moiety exists in a first state in the absence of activity against the target and in a second state in the presence of said activity, and wherein said microbead further comprises a clonal population of one or more chemical structure(s) releasably linked thereto and encoded by said tag.

Disclosed is an encoded chemical library microbead, which microbead has immobilized thereon and/or therein: (i) an encoding tag; and (ii) a target assay system reporter moiety, wherein the reporter moiety exists in a first state in the absence of activity against the target and in a second state in the presence of said activity, and wherein said microbead further comprises a clonal population of one or more chemical structure(s) releasably linked thereto and encoded by said tag.

Provided in some aspects are methods for light-controlled in situ surface patterning of a substrate. Compositions such as nucleic acid arrays produced by the methods are also disclosed. In some embodiments, a method disclosed herein comprises using photoresist for photocontrollable hybridization and/or ligation of nucleic acid molecules, wherein photoresist removal allows hybridization and/or ligation of nucleic acid molecules at the exposed area. A large diversity of barcodes can be created in molecules on the substrate via sequential rounds of light exposure, hybridization, and ligation.

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 disclosure generally relates to compositions and methods for the production of nucleic acid molecules. In some aspects, the invention allows for the microscale generation of nucleic acid molecules, optionally followed by assembly of these nucleic acid molecules into larger molecules. In some aspects, the invention allows for efficient production of nucleic acid molecules (e.g., large nucleic acid molecules such as genomes).

Memory efficient methods determine corrected color values from image data acquired by a nucleic acid sequencer during a base calling cycle. Such methods may: (a) obtain an image of a substrate (e.g., a portion of a flow cell) including a plurality of sites where nucleic acid bases are read; (b) measure color values of the plurality of sites from the image of the substrate; (c) store the color values in a processor buffer of the sequencer's one or more processors; (d) retrieve partially phase-corrected color values of the plurality of sites, where the partially phase-corrected color values were stored in the sequencer's memory during an immediately preceding base calling cycle; (e) determine a prephasing correction; and (f) determine the corrected color values. In various implementations, these operations are all performed during a single base calling cycle. In certain embodiments, the methods additionally include using the corrected color values to make base calls for the plurality of sites. Sequencers may be designed or configured to implement such methods.

Methods and systems for sample preparation techniques that allow amplification (e.g., whole genome amplification) and sequencing of chromatin accessible regions of single cells are provided. The methods and systems generally operate by forming or providing partitions (e.g., droplets) including a single biological particle and a single bead comprising a barcoded oligonucleotide. The preparation of barcoded next-generation sequencing libraries prepared from a single cell is facilitated by the transposon-mediated transposition and fragmentation of a target nucleic acid sequence. The methods and systems may be configured to allow the implementation of single-operation or multi-operation chemical and/or biochemical processing within the partitions.

The present disclosure is concerned with compositions, methods, and kits for preparing a sequencing library. In one embodiment, methods include producing a library of target nucleic acids having the same adapter at each end and then switching the identity of one adapter to result in target nucleic acids flanked by distinct adapters.

In one aspect, the present invention relates to a method for obtaining structural information about an encoded molecule. The encoded molecule may be produced by a reaction of a plurality of chemical entities and may be capable of being connected to an identifier oligonucleotide containing codons informative of the identity of the chemical entities which have participated in the formation of the encoded molecule. In a certain embodiment, primers are designed complementary to the codons appearing on the identifier oligonucleotide, and the presence, absence or relative abundance of a codon is evaluated by mixing a primer with the identifier oligonucleotide in the presence of a polymerase and substrate (deoxy)ribonucleotide triphosphates measuring the extension reaction. In another aspect, the invention provides a method for selecting compounds which binds to a target. More specifically, the invention relates to a method in which a target associated with an oligonucleotide initially is mixed with a library of complexes, each complex comprising a display molecule and an oligonucleotide identifying said display molecule. Next, due an increased proximity, the target oligonucleotide is coupled to the identifier oligonucleotide of complexes having a display molecule with affinity towards the target. In a final stage the coupled nucleotides are analyzed to deduce at least the identity of the display molecule.

This invention provides sets and libraries of short hairpin ribonucleic acid (shRNA) molecules comprising a double-stranded region of random sequence containing random mismatches, methods of generating same, sets and libraries of expression vectors for same, methods of generating same, and methods for identifying an RNA therapeutic or RNA molecule that has an ability to affect a biological parameter, for identifying a drug target for a disease or disorder of interest, and for identifying a variant of an RNA molecule that has an altered ability to affect a biological parameter of interest.