Compositions and methods for identifying antigen-specific T cells, including determining paired T cell receptor sequences for a specific antigen, are described. Compositions and methods for identifying neoantigen-specific T cells are also described. Microfluidic devices useful for identifying antigen-specific T cells, and methods of using the same, are also described.

The disclosure relates to barcoded polymer nanoparticles for in vivo screening and for in vivo therapeutic delivery, and methods therefor. More particularly, the invention relates to polymer nanoparticles, such as reversible addition-fragmentation chain transfer (RAFT) polymer compositions, associated with polynucleotide barcodes, for therapeutic delivery, and for high throughput in vivo screening of drug delivery nanoparticles.

The present invention relates, in part, to methods for selecting subjects for and treating subjects with a type of immunotherapy based on certain biomarkers from the subjects.

Provided herein are methods of determining a surgical margin and the site and size of a tissue to be resected from a subject, and methods of use thereof.

The present disclosure provides methods, systems, and kits for processing nucleic acid molecules. A method may comprise providing a template nucleic acid fragment (e.g., within a cell, cell bead, or cell nucleus) within a partition (e.g., a droplet or well) and subjecting the template nucleic acid fragment to one or more processes including a barcoding process and a single primer extension or amplification process. The processed template nucleic acid fragment may then be recovered from the partition and subjected to further amplification to provide material for subsequent sequencing analysis. The methods provided herein may permit simultaneous processing and analysis of both DNA and RNA molecules originating from the same cell, cell bead, or cell nucleus.

Provided are methods for preparing a library of target nucleic acid sequences, as well as compositions and uses therefor. Methods comprise contacting a nucleic acid sample with a plurality of adaptors capable of amplification of one or more target nucleic acid sequences under conditions wherein the target nucleic acid(s) undergo a first amplification; digesting the resulting first amplification products; repairing the digested target amplicons; and amplifying the repaired products in a second amplification, thereby producing a library of target nucleic acid sequence. Each of the plurality of adaptor compositions comprise a handle and a targeted nucleic acid sequence and optionally one or more tag sequences. Provided methods may be carried out in a single, addition only workflow reaction, allowing for rapid production of highly multiplexed targeted libraries, optionally including unique tag sequences. Resulting library compositions are useful for a variety of applications, including sequencing applications.

Reagents and methods for the analysis of cell free biomolecules (e.g. cell free nucleic acid molecules and cell free polypeptides) of microparticles (e.g. cell-free microparticles originating from blood, or cell-free microparticles originating from an embryo generated by in vitro fertilisation) are provided. Also provided are reagents and methods for the analysis of biomolecules (e.g. nucleic acid molecules and polypeptides) of cells (e.g. cells originating from blood, or cells originating from an embryo generated by in vitro fertilisation). The methods comprise analysing a sample that comprises a microparticle (or cell) or a sample derived from a microparticle (or cell). The methods include methods of measuring at least two linked signals, each signal corresponding to the presence, absence and/or level of a biomolecule of a microparticle (or cell). The methods also include methods of determining the presence, absence and/or level of a biomolecule of a microparticle (or cell) using a barcoded affinity probe. In certain methods both nucleic acid biomolecules and non-nucleic acid biomolecules of a microparticle (or cell) are analysed together. Reagents for use in the methods are also provided.

Provided herein are systems and sets of oligonucleotides for labeling and analyzing nucleic acid molecules that include index barcodes with pre-determined numbers of index positions. Also provided herein are methods for labeling and analyzing nucleic acid molecules, as well as methods of identifying erroneous sequence reads using the sample and molecular barcodes described herein.

Described herein are compositions defective SARS-CoV-2 constructs and particles that can interfere with or block infection of uninfected cells and methods for generating such defective SARS-CoV-2 constructs and particles. The compositions and methods described herein are useful for treatment of SARS-CoV-2 infections.

Methods of uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs, cDNAs, DNAs, proteins, peptides, and/or antigens.