US 12,435,368 B2
Methods and systems for detecting genetic variants
AmirAli Talasaz, Atherton, CA (US); Helmy Eltoukhy, Atherton, CA (US); and Stefanie Ann Ward Mortimer, Morgan Hill, CA (US)
Assigned to Guardant Health, Inc., Palo Alto, CA (US)
Filed by GUARDANT HEALTH, INC., Palo Alto, CA (US)
Filed on Mar. 6, 2025, as Appl. No. 19/072,459.
Application 19/072,459 is a continuation of application No. 18/813,477, filed on Aug. 23, 2024, granted, now 12,286,672.
Application 18/813,477 is a continuation of application No. 18/812,385, filed on Aug. 22, 2024, granted, now 12,258,626.
Application 18/812,385 is a continuation of application No. 18/538,986, filed on Dec. 13, 2023, granted, now 12,098,422, issued on Sep. 25, 2024.
Application 18/538,986 is a continuation of application No. 18/535,485, filed on Dec. 11, 2023, granted, now 12,024,746, issued on Jul. 2, 2024.
Application 18/535,485 is a continuation of application No. 18/491,071, filed on Oct. 20, 2023, granted, now 12,024,745, issued on Jul. 2, 2024.
Application 18/491,071 is a continuation of application No. 18/317,550, filed on May 15, 2023, granted, now 12,098,421, issued on Sep. 24, 2024.
Application 18/317,550 is a continuation of application No. 17/512,587, filed on Oct. 27, 2021, granted, now 11,767,556, issued on Sep. 26, 2023.
Application 17/512,587 is a continuation of application No. 17/410,903, filed on Aug. 24, 2021, granted, now 11,434,531, issued on Sep. 6, 2022.
Application 17/410,903 is a continuation of application No. 17/167,974, filed on Feb. 4, 2021, granted, now 11,149,307, issued on Oct. 19, 2021.
Application 17/167,974 is a continuation of application No. 16/945,124, filed on Jul. 31, 2020, granted, now 11,149,306, issued on Oct. 19, 2021.
Application 16/945,124 is a continuation of application No. 16/601,168, filed on Oct. 14, 2019, granted, now 10,801,063, issued on Oct. 13, 2020.
Application 16/601,168 is a continuation of application No. 15/892,178, filed on Feb. 8, 2018, granted, now 10,883,139, issued on Jan. 5, 2021.
Application 15/892,178 is a continuation of application No. 14/861,989, filed on Sep. 22, 2015, granted, now 9,920,366, issued on Mar. 20, 2018.
Application 14/861,989 is a continuation of application No. PCT/US2014/072383, filed on Dec. 24, 2014.
Claims priority of provisional application 61/948,509, filed on Mar. 5, 2014.
Claims priority of provisional application 61/921,456, filed on Dec. 28, 2013.
Prior Publication US 2025/0230495 A1, Jul. 17, 2025
Int. Cl. C12Q 1/6869 (2018.01); C12Q 1/6886 (2018.01); G16B 15/00 (2019.01)
CPC C12Q 1/6869 (2013.01) [C12Q 1/6886 (2013.01); C12Q 2535/122 (2013.01); C12Q 2600/158 (2013.01); G16B 15/00 (2019.02)] 30 Claims
 
1. A method of monitoring a patient's disease status, wherein the method comprises:
(a) providing a sample comprising double-stranded polynucleotide molecules from the patient, wherein a double-stranded polynucleotide molecule includes first and second complementary strands;
(b) attaching adapters to a plurality of the polynucleotide molecules to generate tagged double-stranded polynucleotide molecules, wherein attaching adapters comprises ligation using more than a 10× excess of adapters as compared to the double-stranded polynucleotide molecules, wherein at least 20% of the double-stranded polynucleotide molecules are attached with adapters;
(c) amplifying a plurality of the tagged double-stranded polynucleotide molecules to produce amplified polynucleotides;
(d) sequencing at least some of amplified polynucleotides to produce a set of sequence reads;
(e) determining an amount of one or more epigenetic modifications from the set of sequence reads, wherein the set of sequence reads comprise paired reads and/or unpaired reads, wherein (i) each paired read corresponds to sequence reads generated from a first tagged strand and a second tagged complementary strand derived from a double-stranded polynucleotide molecule in said set, and (ii) each unpaired read represents a first tagged strand having no second tagged complementary strand derived from a double-stranded polynucleotide molecule represented among said sequence reads in said set of sequence reads; and
(f) repeating (a)-(e) at one or more time points and determining whether there is a difference in the amounts of epigenetic modifications between two or more time points, thereby monitoring a patient's disease status.