US 12,437,840 B2
Determining cell, tissue, or lesion representations in cell-free DNA
Kahn Rhrissorrakrai, Woodside, NY (US); Filippo Utro, Pleasantville, NY (US); Chaya Levovitz, New York, NY (US); and Laxmi Parida, Mohegan Lake, NY (US)
Assigned to International Business Machines Corporation, Armonk, NY (US)
Filed by International Business Machines Corporation, Armonk, NY (US)
Filed on Jul. 2, 2019, as Appl. No. 16/459,948.
Prior Publication US 2021/0005282 A1, Jan. 7, 2021
Int. Cl. G16B 25/10 (2019.01); C12Q 1/6869 (2018.01); G16B 20/00 (2019.01); G16B 25/20 (2019.01); G16B 30/00 (2019.01)
CPC G16B 25/10 (2019.02) [C12Q 1/6869 (2013.01); G16B 20/00 (2019.02); G16B 25/20 (2019.02); G16B 30/00 (2019.02)] 13 Claims
OG exemplary drawing
 
1. A computer-implemented method to determine a cell, tissue or a lesion representation in cell-free DNA from a patient, the computer-implemented method comprising:
obtaining a first and second fluid biopsy samples from the patient;
inputting, to a processor,
a cell-free DNA (cfDNA) genomic profile from the first and second fluid biopsy samples from the patient and
one or more genomic profiles from one or more cells, tissues or lesions from the patient,
wherein the cfDNA genomic profile comprises one or more cfDNA genetic markers and their corresponding cancer cell fraction (CCF) in the one or more fluid biopsy samples,
wherein the genomic profiles from one or more cells, tissues or lesions from the patient comprise the cfDNA genetic markers and their corresponding CCF in the cells, tissues or lesions, and
wherein the cfDNA genetic markers are single nucleotide polymorphisms;
constructing, by the processor, a plurality of synthetic fluid hypotheses (SFs), wherein the plurality of SFs comprises 100,000 or more SFs, and wherein each SF is a hypothetical weighted population per cell, tissue or lesion of the one or more cfDNA genetic markers, wherein weights are determined by a random process;
comparing, by the processor, each of the plurality of SFs to the cfDNA genomic profile to determine goodness of fit, of each of the plurality of SFs to the cfDNA genomic profile;
selecting, by the processor, a subset of the plurality of SFs, wherein each SF of the subset of the plurality of SFs has a minimum distance in goodness of fit compared to the cfDNA genomic profile;
outputting, by the processor, based on the subset of the plurality of SFs, a cell, tissue or a lesion representation in the cfDNA of the patient, wherein the representation correlates the subset of the plurality of SFs with the one or more genomic profiles from the one or more cells, tissues or lesions from the patient to determine the cell, tissue or the lesion representation in the cfDNA of the patient;
using the cell, tissue or the lesion representation in the cfDNA of the patient to assess patient response to a treatment plan by longitudinal monitoring at a lesion level by identifying an initial response of a lesion to the treatment plan prior to the standard assessment grace period for imaging response evaluation of 3 months, wherein the initial response includes a change in the cell, tissue or a lesion representation in the cfDNA of the patient,
wherein the treatment plan is a cancer treatment regimen including at least one subsequent fluid biopsy, the subsequent fluid biopsy being subsequent to the longitudinal monitoring, and one of administration of a chemotherapeutic agent, radiation therapy, surgery, chemotherapy, targeted therapy, hormone therapy, immunotherapy, stem cell transplant, or a combination thereof;
the initial response including at least one lesion of the one or more cells, tissues or lesions having a representation in the cfDNA below a threshold, and
altering the treatment plan by altering the at least one subsequent fluid biopsy to being at least one subsequent solid tumor biopsy of the lesion of the one or more cells; and
performing the subsequent solid tumor biopsy of the lesion of the one or more cells, tissues or lesions.