US 12,590,326 B2 · Methods for fragmentome profiling of cell-free nucleic acids

Abstract

The present disclosure contemplates various uses of cell-free DNA. Methods provided herein may use sequence information in a macroscale and global manner, with or without somatic variant information, to assess a fragmentome profile that can be representative of a tissue of origin, disease, progression, etc. In an aspect, disclosed herein is a method for determining a presence or absence of a genetic aberration in deoxyribonucleic acid (DNA) fragments from cell-free DNA obtained from a subject, the method comprising: (a) constructing a multi-parametric distribution of the DNA fragments over a plurality of base positions in a genome; and (b) without taking into account a base identity of each base position in a first locus, using the multi-parametric distribution to determine the presence or absence of the genetic aberration in the first locus in the subject.

Claims20

Dependent claims

A computer-implemented method for determining a presence or absence of a genetic aberration in deoxyribonucleic acid (DNA) fragments from cell-free DNA obtained from a subject, the method comprising:

(a) obtaining the base sequence of at least 10,000 DNA fragments from the subject, wherein the DNA fragments have been labeled with a unique or non-unique molecular tag, wherein the labeling is performed by ligating sequencing adapters;
(b) constructing, by a computer, a multi-parametric distribution of the DNA fragments over a plurality of base positions in a genome;
and
(c) without taking into account a base identity of each base position in a first locus, using the multi-parametric distribution to determine the presence or absence of the genetic aberration in the first locus in the subject.

1 more element

A computer-implemented method for analyzing cell-free deoxyribonucleic acid (DNA) fragments derived from a subject, the method comprising:

obtaining sequence information representative of the cell-free DNA fragments, wherein the number of DNA fragments is at least 10,000, wherein the DNA fragments have been labeled with a unique or non-unique molecular tag wherein the labeling is performed by ligating sequencing adapters;
and
performing a multi-parametric analysis on a plurality of data sets using the sequence information to generate a multi-parametric model representative of the cell-free DNA fragments, wherein the multi-parametric model comprises three or more dimensions.

Dependencies are inferred from the claim text.

Methods for fragmentome profiling of cell-free nucleic acids

Life of this patent

Methods for fragmentome profiling of cell-free nucleic acids

Life of this patent

Abstract

Claims20