Genetic Copy Number Alteration Classifications

A computer-program product tangibly embodied in a non-transitory machine-readable storage medium, including instructions configured to cause one or more data processors to perform actions including:

• selecting a set of genomic portions each coupled to a sequence read quantification for a test sample, wherein:
• the set of genomic portions comprise portions of a reference genome to which sequence reads obtained for sample nucleic acid from the test subject have been mapped,
• the set of genomic portions comprise (i) genomic portions within a candidate region identified as a candidate copy number variation region, and/or (ii) genomic portions outside the candidate region and within a selected region larger than the candidate region that includes the candidate region, and
• the candidate region is a chromosome or sub-chromosome region;
• shifting a quantification of the sequence reads mapped to the genomic portions for the candidate region at or near a quantification of sequence reads mapped to genomic portions outside the candidate region and within the selected region;
• sampling the genomic portions from the selected region, wherein a number of sampled genomic portions is about equal to a number of genomic portions in the candidate region, thereby generating a sampled region, and repeating the sampling to generate a plurality of sampled regions;
• normalizing a sequence read quantification for each of the sampled regions, thereby generating a normalized quantification for each of the sampled regions;
• generating a confidence determination for the candidate region by a process comprising comparing each normalized quantification to a measure of variability of sequence read quantifications for the candidate region for reference samples not having a significant copy number variation in the candidate region;
• and
• providing a classification for presence or absence of the copy number variation for the candidate region for the test sample according to the confidence determination.

A system comprising:

• one or more data processors;
• and
• a non-transitory computer readable storage medium containing instructions which, when executed on the one or more data processors, cause the one or more data processors to perform actions comprising:
• selecting a set of genomic portions each coupled to a sequence read quantification for a test sample, wherein:
• the set of genomic portions comprise portions of a reference genome to which sequence reads obtained for sample nucleic acid from the test subject have been mapped,
• the set of genomic portions comprise (i) genomic portions within a candidate region identified as a candidate copy number variation region, and/or (ii) genomic portions outside the candidate region and within a selected region larger than the candidate region that includes the candidate region, and
• the candidate region is a chromosome or sub-chromosome region;
• shifting a quantification of the sequence reads mapped to the genomic portions for the candidate region at or near a quantification of sequence reads mapped to genomic portions outside the candidate region and within the selected region;
• sampling the genomic portions from the selected region, wherein a number of sampled genomic portions is about equal to a number of genomic portions in the candidate region, thereby generating a sampled region, and repeating the sampling to generate a plurality of sampled regions;
• normalizing a sequence read quantification for each of the sampled regions, thereby generating a normalized quantification for each of the sampled regions;
• generating a confidence determination for the candidate region by a process comprising comparing each normalized quantification to a measure of variability of sequence read quantifications for the candidate region for reference samples not having a significant copy number variation in the candidate region;
• and
• providing a classification for presence or absence of the copy number variation for the candidate region for the test sample according to the confidence determination.