US 12,437,838 B2
Methods and processes for non-invasive analysis of cell-free fetal nucleic acid according to sequence read quantifications for chromosomes 13, 18, and 21
Cosmin Deciu, San Diego, CA (US); and Zeljko Dzakula, San Diego, CA (US)
Assigned to SEQUENOM, INC., San Diego, CA (US)
Filed by Sequenom, Inc., San Diego, CA (US)
Filed on Oct. 25, 2019, as Appl. No. 16/664,265.
Application 16/664,265 is a continuation of application No. 13/933,935, filed on Jul. 2, 2013, granted, now 10,497,462.
Application 13/933,935 is a continuation of application No. 13/779,638, filed on Feb. 27, 2013, abandoned.
Claims priority of provisional application 61/756,953, filed on Jan. 25, 2013.
Prior Publication US 2020/0168296 A1, May 28, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. G16B 20/10 (2019.01); G16B 20/00 (2019.01); G16B 20/20 (2019.01); G16B 25/00 (2019.01); G16B 25/10 (2019.01); G16B 30/00 (2019.01); G16B 30/10 (2019.01); G16B 30/20 (2019.01)
CPC G16B 20/10 (2019.02) [G16B 20/00 (2019.02); G16B 20/20 (2019.02); G16B 25/00 (2019.02); G16B 25/10 (2019.02); G16B 30/00 (2019.02); G16B 30/10 (2019.02); G16B 30/20 (2019.02)] 8 Claims
 
1. A method comprising:
(a) sequencing circulating cell-free nucleic acid from a test sample from a pregnant subject bearing a fetus by targeted sequencing of chromosomes consisting of chromosome 13, chromosome 18, and chromosome 21, thereby generating sequence reads;
(b) mapping, using a microprocessor, the sequence reads to portions of a reference genome;
(c) counting, using a microprocessor, the sequence reads mapped to the portions;
(d) calculating, using a microprocessor, three ratios from the counts, wherein the three ratios comprise:
(i) a ratio between counts mapped to chromosome 13, or segment thereof, to counts mapped to chromosome 21, or segment thereof,
(ii) a ratio between counts mapped to chromosome 13, or segment thereof, to counts mapped to chromosome 18, or segment thereof, and
(iii) a ratio between counts mapped to chromosome 18, or segment thereof, to counts mapped to chromosome 21, or segment thereof;
(e) comparing the three ratios calculated in (d) with one or more corresponding ratios from one or more euploid reference samples to generate a comparison, wherein the comparing comprises plotting the three ratios calculated in (d) in three dimensions, which dimensions are the ratios, and the comparison is a point for the subject on a three-dimensional plot; and
(f) reporting, based on the comparison, a classification of a presence or absence of a chromosome aneuploidy for the test sample.