US 11,929,146 B2
Systems for non-invasive assessment of chromosome alterations using changes in subsequence mappability
Sung Kim, Glendale, CA (US); Taylor Jacob Jensen, San Diego, CA (US); and Mathias Ehrich, San Diego, CA (US)
Assigned to SEQUENOM, INC., San Diego, CA (US)
Filed by SEQUENOM, INC., San Diego, CA (US)
Filed on Aug. 19, 2019, as Appl. No. 16/544,316.
Application 16/544,316 is a continuation of application No. 15/026,939, granted, now 10,438,691, previously published as PCT/US2014/059156, filed on Oct. 3, 2014.
Claims priority of provisional application 61/887,801, filed on Oct. 7, 2013.
Prior Publication US 2020/0058372 A1, Feb. 20, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. G16B 20/20 (2019.01); G16B 20/00 (2019.01); G16B 20/10 (2019.01); G16B 30/00 (2019.01); G16B 30/10 (2019.01); G16B 30/20 (2019.01)
CPC G16B 20/20 (2019.02) [G16B 20/00 (2019.02); G16B 20/10 (2019.02); G16B 30/00 (2019.02); G16B 30/10 (2019.02); G16B 30/20 (2019.02)] 29 Claims
 
1. A system comprising memory and one or more microprocessors, which memory comprises instructions and which one or more microprocessors are configured to perform, according to the instructions, a process for determining a presence or absence of one or more chromosome alterations in a test sample of nucleic acids, which process comprises:
(a) identifying discordant read pairs from paired-end sequence reads, wherein the paired-end sequence reads are reads of circulating, cell-free nucleic acid from a test subject sample, thereby identifying discordant read mates;
(b) characterizing a mappability of a plurality of sequence read subsequences of each discordant read mate aligned to a reference genome, each of which sequence read subsequences of each discordant read mate is of a different length;
(c) selecting a subset of the discordant read mates according to a change in the mappability, wherein the subset comprises reads comprising a candidate breakpoint;
(d) comparing (i) the number of discordant read mates from the sample associated with the candidate breakpoints and optionally one or more substantially similar breakpoints, to (ii) the number of discordant read mates from a reference associated with the candidate breakpoint and optionally the one or more substantially similar breakpoints, for the discordant read mates in the subset selected in (c), thereby generating a comparison; and
(e) determining the presence or absence of one or more chromosome alterations for the sample according to the comparison in (d).