Guardant Health, Inc.

Ariel Jaimovich

Andrew Kennedy

Darya Chudova

William J Greenleaf

Marcin Sikora

Yupeng He

Stephen Fairclough

Oscar Westesson

Sven Jeffrey Duenwald

Charbel Said Eid

Haley Dara Axelrod

Peter Vilem Grauman

Matthew Schultz

Disclosed herein are methods for isolating DNA, such as cell-free DNA (cfDNA) or DNA from a tissue sample, e.g., in which the DNA is partitioned into hypermethylated and hypomethylated partitions. After differential tagging of the partitions, portions of the hypomethylated partition are pooled with the hypermethylated partition or pooled separately. Epigenetic and sequence-variable target regions are captured from the pool comprising DNA from the hypermethylated and hypomethylated partitions, and sequence-variable target regions are captured from the pool comprising DNA from the hypomethylated partition. This approach can reduce costs and/or bandwidth by limiting sequencing of epigenetic target regions from the hypomethylated partition, which may be less informative than other DNA.

Methods for isolating cell-free DNA

In an aspect, a method for detecting the presence or absence of cancer in a subject comprises: (a) obtaining samples from the subject from different time points, wherein a first sample obtained at first time point is a polynucleotide sample from a tumor tissue specimen and a second sample obtained at second time point is a cell-free polynucleotide sample from a blood sample; (b) processing polynucleotides from each of the samples, comprising: i) tagging at least a portion of the polynucleotides, thereby generating tagged parent polynucleotides; ii) amplifying at least a portion of the tagged parent polynucleotides to generate progeny polynucleotides; iii) enriching at least a portion of the progeny polynucleotides for target genomic regions; thereby generating enriched polynucleotides; and iv) sequencing at least a portion of the enriched polynucleotides to generate sequencing reads; and (c) analyzing genomic regions for at least one epigenetic feature from the sequencing reads.

Methods and systems for improving patient monitoring after surgery

Sequencing nucleic acids can identify variations associated with presence, susceptibility or prognosis of disease. However, the value of such information can be compromised by errors introduced by or before the sequencing process including preparing nucleic acids for sequencing. Blunting single-stranded overhangs on nucleic acids in a sample can introduce deamination-induced sequencing errors. The disclosure provides methods of identifying and correcting for such deamination-induced sequencing errors and distinguishing them from real sequence variations.

Correcting for deamination-induced sequence errors

Disclosed herein are compositions and methods for isolating DNA, such as cell-free DNA (cfDNA). In some embodiments, the cell-free DNA is from a subject having or suspected of having cancer and/or the cell-free DNA comprises DNA produced by a tumor. In some embodiments, the DNA isolated by the method is captured using a sequence-variable target region set and an epigenetic target region set, wherein the sequence-variable target region set is captured with a greater capture yield than the epigenetic target region set. In some embodiments, captured cfDNA of the sequence-variable target region set is sequenced to a greater depth of sequencing than captured cfDNA of the epigenetic target region set.

Compositions and methods for isolating cell-free DNA

Growing community of inventors

Redwood City, CA, United States of America

Ariel Jaimovich