Methods and processes for non-invasive assessment of genetic variations

A computer-implemented method for classifying nucleic acid for a fetal aneuploidy, comprising:

• (a) identifying a subset of genomic sections of a reference genome consisting essentially of genomic sections to which an enriched amount of reads from fetal nucleic acid fragments are mapped by a process comprising:
• (i) sequencing circulating cell-free nucleic acid from each sample from a group of pregnant females by a sequencer that generates sequence reads for each of the samples of the group;
• (ii) measuring, for each of the samples of the group, the length of each fragment in the circulating cell-free nucleic acid from which each of the sequence reads originated using a microprocessor;
• (iii) computing, using a microprocessor, a fragment length ratio X/Y for each genomic section for each sample, wherein:
• (1) X is the sum of reads that (i) map to the genomic section, and (ii) are from nucleic acid fragments that are shorter than a first selected fragment length;
• and
• (2) Y is the sum of reads that (i) map to the genomic section, and (ii) are from nucleic acid fragments that are shorter than a second selected fragment length, wherein the second selected fragment length is longer than the first selected fragment length;
• (iv) computing an average fragment length ratio for each genomic section;
• (v) determining a median fragment length ratio for a plurality of genomic sections;
• and
• (vi) selecting the subset of genomic sections based on each genomic section of the subset having an average fragment length ratio that is greater than the median fragment length ratio;
• (b) sequencing circulating cell-free nucleic acid from a test sample from a pregnant female bearing a fetus by a sequencer that generates sequence reads for the test sample;
• (c) mapping, using a microprocessor, the test sample sequence reads to the subset of genomic sections selected in (a)(vi);
• (d) calculating, using a microprocessor, the amount of test sample sequence reads mapped to the subset of genomic sections;
• (e) outputting a classification of presence or absence of a fetal aneuploidy according to the amount determined in (d).