The invention provides methods of isolating a target nucleic acid in a sample. A primer is hybridized to the target. A polymerase and modified nucleotide resistant to nuclease degradation are used to extend the primer to create a modified polynucleotide. The sample is exposed to a nuclease, thereby isolating the modified polynucleotide. Optionally, the target nucleic acid may be further protected by binding a protein in a sequence specific manner to one end of the target nucleic acid to create a protected target nucleic acid resistant to nuclease degradation. Thus, after exposing the sample to a nuclease, the modified polynucleotide and protected target nucleic acid are isolated.

The invention provides methods of isolating a target nucleic acid in a sample. A primer is hybridized to the target. A polymerase and modified nucleotide resistant to nuclease degradation are used to extend the primer to create a modified polynucleotide. The sample is exposed to a nuclease, thereby isolating the modified polynucleotide. Optionally, the target nucleic acid may be further protected by binding a protein in a sequence specific manner to one end of the target nucleic acid to create a protected target nucleic acid resistant to nuclease degradation. Thus, after exposing the sample to a nuclease, the modified polynucleotide and protected target nucleic acid are isolated.

The invention provides methods of isolating a target nucleic acid in a sample. A primer is hybridized to the target. A polymerase and modified nucleotide resistant to nuclease degradation are used to extend the primer to create a modified polynucleotide. The sample is exposed to a nuclease, thereby isolating the modified polynucleotide. Optionally, the target nucleic acid may be further protected by binding a protein in a sequence specific manner to one end of the target nucleic acid to create a protected target nucleic acid resistant to nuclease degradation. Thus, after exposing the sample to a nuclease, the modified polynucleotide and protected target nucleic acid are isolated.

Methods for performing multiplex PCR-based enrichment of a target substrate are provided. Systems and methods for generating a sequencing library are also provided.

Methods for performing multiplex PCR-based enrichment of a target substrate are provided. Systems and methods for generating a sequencing library are also provided.

A method for selectively modifying a target polynucleotide in a sample of polynucleotides, the method comprising contacting a sample of polynucleotides with a guide polynucleotide that binds to a sequence in the target polynucleotide and a polynucleotide-guided effector protein such that the polynucleotide-guided effector protein cuts the target polynucleotide to produce a cut end comprising an overhang; and attaching an adapter to the cut end in the target polynucleotide.

A method for selectively modifying a target polynucleotide in a sample of polynucleotides, the method comprising contacting a sample of polynucleotides with a guide polynucleotide that binds to a sequence in the target polynucleotide and a polynucleotide-guided effector protein such that the polynucleotide-guided effector protein cuts the target polynucleotide to produce a cut end comprising an overhang; and attaching an adapter to the cut end in the target polynucleotide.

This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors.

This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors.

Methods of detecting target polynucleotide sequences may include introducing one or more nucleic acid analytes to a first reaction mixture comprising a single-stranded probe oligonucleotide A.sub.0, a pyrophosphorolysing enzyme, and a ligase. The analyte may anneal to the single-stranded probe oligonucleotide A.sub.0 to create a first intermediate product which is at least partially double-stranded, where the 3′ end of A.sub.0 forms a double-stranded complex with the analyte and where A.sub.0 is pyrophosphorylsed in the 3′-5′ direction from the 3′ end to create at least a partially digested strand A.sub.1. A.sub.1 may undergo ligation to form oligonucleotide A.sub.2. The methods may also include detecting a signal derived from the formed oligonucleotides, and inferring therefrom the presence or absence of the target polynucleotide sequence in the analyte.