The quality of cell-free DNA for analysis is improved by techniques described herein. Cell-free DNA may include DNA with defects that do not allow for analysis of those DNA with techniques such as sequencing and targeted capture enrichment. These defects may be defects within the strands of the DNA and not present at the ends of the DNA. These intrastrand defects in cell-free DNA can be repaired. The repair of the defects in cell-free DNA may then allow for these repaired cell-free DNA to be analyzed by techniques, including sequencing and targeted capture enrichment.

Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof for sequencing a nucleic acid.

Compositions comprising covalently modified and mutated biotin-binding proteins, particularly biotin-binding proteins having a negative charge at physiological pH, are provided. Methods of producing such proteins are also provided, as are methods of immobilizing, sequencing, and making nucleic acids employing such proteins.

This disclosure provides methods for monitoring an immune response. Methods comprise linking a polynucleotide sequence encoding a heavy chain variable region and a polynucleotide sequence encoding a light chain variable region from a single lymphocyte from a biological sample obtained before an immune response and linking a polynucleotide sequence encoding a heavy chain variable region and a polynucleotide sequence encoding a light chain variable region from a single lymphocyte from a biological sample obtained during or after an immune response. Methods further comprise performing high-throughput sequencing of the linked (paired) sequences from before the immune response and from during or after the immune response, and comparing the resulting sequence reads.

Compositions comprising covalently modified and mutated biotin-binding proteins, particularly biotin-binding proteins having a negative charge at physiological pH, are provided. Methods of producing such proteins are also provided, as are methods of immobilizing, sequencing, and making nucleic acids employing such proteins.

The present invention relates to a method of identifying a target genomic nucleic acid sequence including hybridizing a set of probes to the target genomic nucleic acid sequence, wherein the set of probes has a unique associated barcode sequence for identification of the target genomic nucleic acid sequence, wherein each probe of the set includes (1) a complementary sequence complementary to a first strand of the target genomic nucleic acid sequence and (2) the associated barcode sequence or a portion of the associated barcode sequence, sequencing the associated barcode sequence from probes hybridized to the target genomic nucleic acid sequence using a fluorescence-based sequencing method, and identifying the target genomic nucleic acid sequence by the sequenced barcode sequence.

The present invention relates to a method of identifying a target genomic nucleic acid sequence including hybridizing a set of probes to the target genomic nucleic acid sequence, wherein the set of probes has a unique associated barcode sequence for identification of the target genomic nucleic acid sequence, wherein each probe of the set includes (1) a complementary sequence complementary to a first strand of the target genomic nucleic acid sequence and (2) the associated barcode sequence or a portion of the associated barcode sequence, sequencing the associated barcode sequence from probes hybridized to the target genomic nucleic acid sequence using a fluorescence-based sequencing method, and identifying the target genomic nucleic acid sequence by the sequenced barcode sequence.

Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof for sequencing a nucleic acid.

Disclosed herein include methods and systems for identifying multiplet expression profiles. A plurality of synthetic multiplet expression profiles can be generated from a plurality of expression profiles. An expression profile can be identified as an expression for a singlet or a multiplet using a machine learning model trained using the plurality of synthetic multiplet (e.g., doublet) expression profiles.

Disclosed herein include methods and systems for identifying multiplet expression profiles. A plurality of synthetic multiplet expression profiles can be generated from a plurality of expression profiles. An expression profile can be identified as an expression for a singlet or a multiplet using a machine learning model trained using the plurality of synthetic multiplet (e.g., doublet) expression profiles.