Disclosed are methods, assays, and kits for identifying a ligand to a biological molecule, such as a protein, a lipid, a carbohydrate, or a nucleic acid. The disclosed methods may be a quantitative binding assay against targets, which sidesteps the challenge of target purification, and may provide a systematic approach to discover and target allosteric binding sites.

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.

The present disclosure provides methods of processing or analyzing a sample. A method for processing a sample may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule), barcoding the probe-nucleic acid molecule complex, and performing extension, denaturation, and amplification processes. A method for processing a sample may comprise hybridizing first and second probes to adjacent or non-adjacent target regions of a nucleic acid molecule (e.g., an RNA molecule), linking the first and second probes to provide a probe-linked nucleic acid molecule, and barcoding the probe-linked nucleic acid molecule. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well. One or more processes of the methods described herein may be performed on a cell, such as a permeabilized cell.

The present invention relates to methods of selecting, screening, engineering, making and modifying antibodies that have improved bioavailability upon subcutaneous administration to a human. Antibodies and variant antibodies with improved bioavailability upon subcutaneous administration to a human are also described.

The present invention relates to the analysis of complex single cell sequencing libraries. Disclosed are methods for enrichment of library members based on the presence of cell-of origin barcodes to identify and concentrate DNA that is relevant to interesting cells or components that would be expensive or difficult to study otherwise. Also, disclosed are methods of capturing cDNA library molecules by use of CRISPR systems, hybridization or PCR. The present invention allows for identifying the properties of rare cells in single cell RNA-seq data and accurately profile them through clustering approaches. Further information on transcript abundances from subpopulations of single cells can be analyzed at a lower sequencing effort. The methods also allow for linking TCR alpha and beta chains at the single cell level.

The present invention relates to the analysis of complex single cell sequencing libraries. Disclosed are methods for enrichment of library members based on the presence of cell-of origin barcodes to identify and concentrate DNA that is relevant to interesting cells or components that would be expensive or difficult to study otherwise. Also, disclosed are methods of capturing cDNA library molecules by use of CRISPR systems, hybridization or PCR. The present invention allows for identifying the properties of rare cells in single cell RNA-seq data and accurately profile them through clustering approaches. Further information on transcript abundances from subpopulations of single cells can be analyzed at a lower sequencing effort. The methods also allow for linking TCR alpha and beta chains at the single cell level.

[Problem] Provided are a production method for a multi-input/multi-output-type genetic switch or a transcription factor, and a multi-input/multi-output-type genetic switch or a transcription factor. [Solving Means] The inventors of the present invention have completed a production method for a multi-input/multi-output-type genetic switch or a transcription factor, essentially including the steps of “fusing two or more transcription factor genes to each other” and “introducing mutations into the fusion-type transcription factor gene,” and have further succeeded in obtaining a multi-input/multi-output-type genetic switch or a transcription factor by the method.

[Problem] Provided are a production method for a multi-input/multi-output-type genetic switch or a transcription factor, and a multi-input/multi-output-type genetic switch or a transcription factor. [Solving Means] The inventors of the present invention have completed a production method for a multi-input/multi-output-type genetic switch or a transcription factor, essentially including the steps of “fusing two or more transcription factor genes to each other” and “introducing mutations into the fusion-type transcription factor gene,” and have further succeeded in obtaining a multi-input/multi-output-type genetic switch or a transcription factor by the method.

Provided herein are methods for labeling input DNA with oligonucleotide barcode sequences, and selective PCR amplification of DNA sequence variants across the targeted regions for variant quantitation.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.