US 12,203,142 B2
Detecting mutations and ploidy in chromosomal segments
Joshua Babiarz, Castro Valley, CA (US); Tudor Pompiliu Constantin, Berkeley, CA (US); Lane A. Eubank, San Carlos, CA (US); George Gemelos, Portland, OR (US); Matthew Micah Hill, Belmont, CA (US); Huseyin Eser Kirkizlar, Los Angeles, CA (US); Matthew Rabinowitz, San Francisco, CA (US); Onur Sakarya, Redwood City, CA (US); Styrmir Sigurjonsson, San Jose, CA (US); and Bernhard Zimmermann, Manteca, CA (US)
Assigned to Natera, Inc., San Carlos, CA (US)
Filed by Natera, Inc., San Carlos, CA (US)
Filed on May 30, 2024, as Appl. No. 18/678,577.
Application 18/678,577 is a continuation of application No. 17/692,469, filed on Mar. 11, 2022.
Application 17/692,469 is a continuation of application No. 15/898,145, filed on Feb. 15, 2018, granted, now 11,319,595, issued on May 3, 2022.
Application 15/898,145 is a continuation of application No. 14/692,703, filed on Apr. 21, 2015, granted, now 10,179,937, issued on Jan. 15, 2019.
Claims priority of provisional application 61/982,245, filed on Apr. 21, 2014.
Claims priority of provisional application 61/987,407, filed on May 1, 2014.
Claims priority of provisional application 61/994,791, filed on May 16, 2014.
Claims priority of provisional application 62/066,514, filed on Oct. 21, 2014.
Claims priority of provisional application 62/146,188, filed on Apr. 10, 2015.
Claims priority of provisional application 62/147,377, filed on Apr. 14, 2015.
Claims priority of provisional application 62/148,173, filed on Apr. 15, 2015.
Prior Publication US 2024/0309464 A1, Sep. 19, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/6886 (2018.01); C12Q 1/6869 (2018.01); G06N 7/01 (2023.01); G06N 20/00 (2019.01); G16B 15/00 (2019.01); G16B 20/00 (2019.01); G16B 20/10 (2019.01); G16B 20/20 (2019.01); G16B 25/00 (2019.01); G16B 40/00 (2019.01); G16B 40/20 (2019.01); G16H 10/40 (2018.01); G16H 50/20 (2018.01); G16Z 99/00 (2019.01); G16B 25/20 (2019.01)
CPC C12Q 1/6886 (2013.01) [C12Q 1/6869 (2013.01); G06N 7/01 (2023.01); G06N 20/00 (2019.01); G16B 15/00 (2019.02); G16B 20/00 (2019.02); G16B 20/10 (2019.02); G16B 20/20 (2019.02); G16B 25/00 (2019.02); G16B 40/00 (2019.02); G16B 40/20 (2019.02); G16H 10/40 (2018.01); G16H 50/20 (2018.01); G16Z 99/00 (2019.02); C12Q 2539/10 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/16 (2013.01); C12Q 2600/172 (2013.01); G16B 25/20 (2019.02)] 30 Claims
 
1. A method for preparing a sample of a subject having cancer or suspected of having cancer useful for identifying one or more tumor-specific variants in a blood, plasma, serum, or urine sample, the method comprising:
(a) performing whole exome sequencing or whole genome sequencing on nucleic acids derived from a tumor sample of the subject and identifying 100 to 20,000 tumor-specific variants;
(b) selectively enriching 100 to 20,000 target loci from cell-free DNA derived from a blood, plasma, serum, or urine sample of the subject to obtain selectively enriched DNA, wherein the 100 to 20,000 of the target loci each encompasses one of the tumor-specific variants identified in the tumor sample of the subject, wherein the selective enrichment of the target loci is performed using 100 to 20,000 target-specific primers or probes in the same reaction mixture; and
(c) sequencing the selectively enriched DNA and obtaining sequence reads with a depth of read of at least 10,000 per target locus, and identifying one or more of the tumor-specific variants present in the cell-free DNA from the sequence reads.