US 11,913,065 B2
Systems and methods to detect rare mutations and copy number variation
AmirAli Talasaz, Atherton, CA (US); and Stefanie Ann Ward Mortimer, Morgan Hill, CA (US)
Assigned to Guardent Health, Inc., Palo Alto, CA (US)
Filed by GUARDANT HEALTH, INC., Redwood City, CA (US)
Filed on Dec. 12, 2019, as Appl. No. 16/711,892.
Application 16/711,892 is a continuation of application No. 15/669,779, filed on Aug. 4, 2017, granted, now 10,894,974.
Application 15/669,779 is a continuation of application No. 15/076,565, filed on Mar. 21, 2016, granted, now 9,902,992, issued on Feb. 27, 2018.
Application 15/076,565 is a continuation of application No. 14/855,301, filed on Sep. 15, 2015, abandoned.
Application 14/855,301 is a continuation of application No. PCT/US2014/000048, filed on Mar. 15, 2014.
Application PCT/US2014/000048 is a continuation in part of application No. 13/969,260, filed on Aug. 16, 2013, abandoned.
Application PCT/US2014/000048 is a continuation in part of application No. PCT/US2013/058061, filed on Sep. 4, 2013.
Claims priority of provisional application 61/948,530, filed on Mar. 5, 2014.
Claims priority of provisional application 61/845,987, filed on Jul. 13, 2013.
Claims priority of provisional application 61/793,997, filed on Mar. 15, 2013.
Claims priority of provisional application 61/704,400, filed on Sep. 21, 2012.
Claims priority of provisional application 61/696,734, filed on Sep. 4, 2012.
Prior Publication US 2020/0224254 A1, Jul. 16, 2020
Prior Publication US 2022/0170082 A9, Jun. 2, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/6827 (2018.01); G16B 30/00 (2019.01); C12Q 1/6806 (2018.01); C12Q 1/6869 (2018.01)
CPC C12Q 1/6827 (2013.01) [C12Q 1/6806 (2013.01); G16B 30/00 (2019.02); C12Q 1/6869 (2013.01)] 20 Claims
 
1. A method for sequencing polynucleotides derived from a population of cell-free nucleic acids from a sample of a subject, the method comprising:
(a) ligating a plurality of the cell-free nucleic acids with molecular barcodes from a set of molecular barcodes to produce tagged parent polynucleotides,
wherein ligating comprises using more than a 10X molar excess of molecular barcodes as compared to the cell-free nucleic acids in the population, and
wherein at least 20% of the cell-free nucleic acids from the population are attached to molecular barcodes at both ends of a molecule of the cell-free nucleic acids;
(b) amplifying a plurality of the tagged parent polynucleotides to generate amplified progeny polynucleotides; and
(c) sequencing at least a subset of the amplified progeny polynucleotides to generate sequencing reads representing sequences of the amplified progeny polynucleotides, wherein a plurality of the sequencing reads comprises sequences of the molecular barcodes and of the cell-free nucleic acids.