US 11,746,385 B2
Methods of detecting tumor progression via analysis of cell-free nucleic acids
Abhik Shah, San Francisco, CA (US)
Assigned to Lexent Bio, Inc., San Francisco, CA (US)
Filed by Lexent Bio, Inc., San Francisco, CA (US)
Filed on May 18, 2020, as Appl. No. 16/876,533.
Claims priority of provisional application 62/850,808, filed on May 21, 2019.
Prior Publication US 2020/0377960 A1, Dec. 3, 2020
Int. Cl. C12Q 1/6886 (2018.01)
CPC C12Q 1/6886 (2013.01) [C12Q 2600/112 (2013.01); C12Q 2600/156 (2013.01)] 41 Claims
 
1. A method for monitoring tumor progression or tumor non-progression of a tumor of a subject, comprising:
measuring, by a processor, a count of a plurality of cell-free DNA (cfDNA) molecules at each of a plurality of genomic regions, wherein the plurality of cfDNA molecules is obtained or derived from a bodily fluid sample of the subject at a first timepoint;
processing, by the processor, the plurality of cfDNA counts measured at each of the plurality of genomic regions to obtain quantitative measures of deviation of the plurality of counts relative to a plurality of reference values to produce a plurality of deviation scores of the subject, wherein the plurality of reference values comprises an additional plurality of counts obtained from additional cfDNA molecules obtained or derived from additional bodily fluid samples of additional subjects that are unaffected by cancer or without a diagnosis of cancer;
determining, by the processor, a difference between the plurality of deviation scores and a plurality of reference deviation scores to produce a plurality of changes in deviation (CID) values, wherein the reference deviation scores are a baseline set of deviation values generated from additional subjects that are unaffected by cancer or without a diagnosis of cancer, and applying a logarithmic transformation to a sum of the plurality of CID values to produce a CID score;
measuring, by the processor, a second count of a second plurality of cfDNA molecules at each of the plurality of genomic regions, wherein the second plurality of cfDNA molecules is obtained or derived from a bodily fluid sample of the subject at a second timepoint after the first timepoint;
processing, by the processor, the plurality of second counts measured at each of the plurality of genomic regions to obtain second quantitative measures of deviation of the second plurality of counts relative to the plurality of reference values to produce a second plurality of deviation scores;
determining, by the processor, a difference between the second plurality of deviation scores and the second plurality of reference deviation scores to produce a second plurality of changes in deviation (CID) values, and applying a logarithmic transformation to a sum of the second plurality of CID values to produce a second CID score; and
determining, by the processor, a difference between the first and second CID scores, said difference being indicative of tumor progression or tumor non-progression of the tumor of the subject, wherein when the difference between the first and second CID scores is greater than zero, the difference is indicative of tumor progression.