Method for determining copy number variations in sex chromosomes

A system for evaluation of copy number of a genetic sequence of interest in a test sample, the system comprising:

• a sequencer for receiving nucleic acids from the test sample providing nucleic acid sequence information from the sample;
• a processor;
• and
• one or more computer-readable storage media having stored thereon instructions for execution on said processor to evaluate the copy number of the Y chromosome in the test sample using a reference sequence of the Y chromosome filtered by a mask,
• wherein
• the mask comprises bins of specific size on the reference sequence of the Y chromosome,
• the bins have more than a threshold number of training sequence tags aligned thereto, and
• the training sequence tags comprise genomic reads from a first plurality of female individuals aligned to the reference sequence of the Y chromosome.

A computer program product comprising one or more computer-readable non-transitory storage media having stored thereon computer-executable instructions that, when executed by one or more processors of a computer system, cause the computer system to implement a method for evaluation of copy number of the Y chromosome in a test sample comprising fetal and maternal cell-free nucleic acids, the method comprising:

• providing, on the computer system, a training set comprising genomic reads measured from nucleic acid samples of a first plurality of female individuals;
• aligning, by the computer system, at least about 100,000 genomic reads per individual of the training set to a reference sequence of the Y-chromosome, thereby providing training sequence tags comprising aligned genomic reads and their locations on the reference sequence of the Y chromosome;
• dividing, by the computer system, the reference sequence of the Y chromosome into bins of a specific size;
• determining, by the computer system, counts of training sequence tags located in each bin;
• masking, by the computer system, bins that exceed a masking threshold, the masking threshold being based on the counts of training sequence tags in each bin, thereby providing a masked reference sequence of the Y chromosome for evaluation of copy number of the Y chromosome in the test sample comprising fetal and maternal cell-free nucleic acids.