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.

Provided are a sequencing library and applications thereof. The provided sequencing library includes a first nucleic acid molecule and a second nucleic acid molecule. The first nucleic acid molecule carries a cell index sequence and a droplet index sequence. The second nucleic acid molecule carries an insert fragment and a cell index sequence.

The present disclosure provides for endonuclease enzymes as well as methods of using such enzymes or variants thereof.

The present disclosure relates to systems, compositions and methods for modifying target nucleic acid sequences.

Aspects of the present disclosure relate generally to methods, compositions, and kits for in situ whole cell barcoding. Aspects of the present disclosure also include a computer readable-medium and a processor to carry out the steps of the method described herein. In some embodiments, the disclosure relates to whole cell barcoding performed in situ.

Described is an assay termed Programmable Enzyme-Assisted Selective Exponential Amplification (PASEA) that concurrently amplifies both wild type and mutant alleles while selectively cleaving the former. With time, the rare mutant alleles dominate, and are readily detectable by direct detection, Sanger sequencing, and other readily available methods. Also described are point-of-care assays and microfluidic devices for performing PASEA.

Provided herein are automated apparatus for the identification of microorganisms in various samples. The disclosure solves existing challenges encountered in identifying and distinguishing various types of microorganisms, including viruses and bacteria in a timely, efficient, and automated manner by sequencing.

Described herein are methods for determining a sequence of a region of interest from an mRNA molecule. Sequenced polynucleotides can include a barcode region, a homopolymer region (e.g., a poly-A region), and a target region associated with the mRNA molecule. According to some methods, the barcode region omits the same base present in the homopolymer region. According to some methods, extension of the primer used for sequencing is stalled within the homopolymer region. According to some methods, sequencing flow cycles and the different barcode regions of the polynucleotides configured are such that the primer is extended to the end of the barcode region across the plurality of polynucleotides before being extended into the homopolymer region. According to some methods, two primers or a cleavable primer is used to separately sequence the barcode region and the target region.

This invention relates to a method for the purification of nucleic acids, preferably DNA, from biological samples, comprising the steps (a) optional lysis of said sample, (b) optional heat incubation of said sample, (c) enzymatic digestion of non-nucleic acid components in the product of step (a) or (b), (d) heat inactivation of one or more enzyme(s) used in step (c), (e) transfer of the product of step (d) onto a resin capable of retaining non-nucleic acid components, while the nucleic acids pass through the resin, thereby purifying the nucleic acids.

This invention relates to a method for the purification of nucleic acids, preferably DNA, from biological samples, comprising the steps (a) optional lysis of said sample, (b) optional heat incubation of said sample, (c) enzymatic digestion of non-nucleic acid components in the product of step (a) or (b), (d) heat inactivation of one or more enzyme(s) used in step (c), (e) transfer of the product of step (d) onto a resin capable of retaining non-nucleic acid components, while the nucleic acids pass through the resin, thereby purifying the nucleic acids.