Analyzing copy number variation in the detection of cancer

A computer-implemented method comprising, by one or more processors of a computer system:

• receiving sequence reads of nucleic acids in a test sample from a mammal, the test sample comprising both genomic nucleic acids from cancerous or precancerous cells and genomic nucleic acids from constitutive cells;
• aligning the sequence reads to one or more chromosome reference sequences, thereby providing sequence tags corresponding to the sequence reads;
• identifying a number of sequence tags for one or more sequences of interest amplification of which or deletions of which are associated with cancers, wherein the one or more sequences of interest are on chromosomes 1-22, X, or Y sequences;
• identifying a number of sequence tags for at least one normalizing sequence for each of the one or more sequences of interest;
• wherein the at least one normalizing sequence is a sequence that yields sequence doses for a sequence of interest having:
• (a) the smallest variability among unaffected samples, (b) the greatest differentiability between affected and unaffected samples, (c) the smallest variability and the greatest differentiability, or (d) an optimal combination of small variability and large differentiability;
• determining, based on the number of sequence tags identified for each of the one or more sequences of interest and the number of sequence tags identified for the at least one normalizing sequence, a sequence dose for each of the one or more sequences of interest;
• and
• determining, based on the sequence dose and a corresponding threshold value for each of the one or more sequences of interest, a presence or absence of copy number variations (CNVs) of the one or more sequences of interest in the test sample, the presence of the CNVs being an indicator of a presence and/or increased risk of a cancer.

A system comprising:

• one or more processors;
• and
• one or more processor-readable media storing instructions which, when executed by the one or more processors, cause performance of operations including:
• receiving sequence reads of nucleic acids in a test sample from a mammal, the test sample comprising both genomic nucleic acids from cancerous or precancerous cells and genomic nucleic acids from constitutive cells;
• aligning the sequence reads to one or more chromosome reference sequences, thereby providing sequence tags corresponding to the sequence reads;
• identifying a number of sequence tags for one or more sequences of interest amplification of which or deletions of which are associated with cancers, wherein the one or more sequences of interest are on chromosomes 1-22, X, or Y sequences;
• identifying a number of sequence tags for at least one normalizing sequence for each of the one or more sequences of interest;
• wherein the at least one normalizing sequence is a sequence that yields sequence doses for a sequence of interest having:
• (a) the smallest variability among unaffected samples, (b) the greatest differentiability between affected and unaffected samples, (c) the smallest variability and the greatest differentiability, or (d) an optimal combination of small variability and large differentiability;
• determining, based on the number of sequence tags identified for each of the one or more sequences of interest and the number of sequence tags identified for the at least one normalizing sequence, a sequence dose for each of the one or more sequences of interest;
• and
• determining, based on the sequence dose and a corresponding threshold value for each of the one or more sequences of interest, a presence or absence of copy number variations (CNVs) of the one or more sequences of interest in the test sample, the presence of the CNVs being an indicator of a presence and/or increased risk of a cancer.

One or more non-transitory processor-readable media storing instructions which, when executed by one or more processors of a computer system, cause performance of operations comprising:

• receiving sequence reads of nucleic acids in a test sample from a mammal, the test sample comprising both genomic nucleic acids from cancerous or precancerous cells and genomic nucleic acids from constitutive cells;
• aligning the sequence reads to one or more chromosome reference sequences, thereby providing sequence tags corresponding to the sequence reads;
• identifying a number of sequence tags for one or more sequences of interest amplification of which or deletions of which are associated with cancers, wherein the one or more sequences of interest are on chromosomes 1-22, X, or Y sequences;
• identifying a number of sequence tags for at least one normalizing sequence for each of the one or more sequences of interest;
• wherein the at least one normalizing sequence is a sequence that yields sequence doses for a sequence of interest having:
• (a) the smallest variability among unaffected samples, (b) the greatest differentiability between affected and unaffected samples, (c) the smallest variability and the greatest differentiability, or (d) an optimal combination of small variability and large differentiability;
• determining, based on the number of sequence tags identified for each of the one or more sequences of interest and the number of sequence tags identified for the at least one normalizing sequence, a sequence dose for each of the one or more sequences of interest;
• and
• determining, based on the sequence dose and a corresponding threshold value for each of the one or more sequences of interest, a presence or absence of copy number variations (CNVs) of the one or more sequences of interest in the test sample, the presence of the CNVs being an indicator of a presence and/or increased risk of a cancer.