Guardant Health, Inc.
METHODS, COMPOSITIONS AND SYSTEMS FOR IMPROVING THE BINDING OF METHYLATED POLYNUCLEOTIDES

Abstract:

In an aspect, a method for detecting the presence or absence of tumor in a polynucleotide sample obtained from a subject comprising: (i) adding carrier nucleic acid molecules to the polynucleotide sample to generate a first sample; wherein the set of carrier nucleic acid molecules comprises at least one subset of unmethylated carrier nucleic acid molecules and/or at least one subset of methylated carrier nucleic acid molecules and at least one end of the carrier nucleic acid molecules is modified to prevent ligation; (ii) partitioning the first sample into at least two partitioned sets using capturing agent that binds selectively to methylated polynucleotides; (iii) processing the partitioned sample to generate processed sample, wherein the processing comprises: tagging, amplifying and enriching; (iv) sequencing the processed sample to generate a set of sequencing reads; and (v) analyzing a plurality of sequencing reads to detect the presence or absence of tumor.