Patent ID: 11929146
Assignee: SEQUENOM, INC.
Field: Computer technology (Electrical engineering)
Classification: CPC G | IPC G

Claim 27:
28. A system comprising a sequencing apparatus and one or more computing apparatus,
which sequencing apparatus is configured to produce signals corresponding to nucleotide bases of a nucleic acid loaded in the sequencing apparatus, which nucleic acid is circulating cell-free nucleic acid from a test subject sample, or which nucleic acid loaded in the sequencing apparatus is a modified variant of the circulating cell-free nucleic acid; and
which one or more computing apparatus comprise memory and one or more processors,
which memory comprises instructions executable by the one or more processors and which instructions executable by the one or more processors are configured to:
(a) produce paired-end sequence reads from the signals and align the sequence reads to a reference genome;
(b) identify discordant read pairs from the paired-end sequence reads, thereby identifying discordant read mates;
(c) characterize 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;
(d) select a subset of the discordant read mates according to a change in mappability, wherein the subset comprises reads comprising a candidate breakpoint;
(e) compare (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
(f) determine a presence or absence of one or more chromosome alterations for the sample according to the comparison in (d).