Analyzing copy number variation in the detection of cancer

A method, implemented using a computer system comprising one or more processors and system memory, for identifying the presence of a cancer and/or an increased risk of a cancer in a mammal, said method comprising:

• (a) providing, to the computer system, at least 10,000 sequence reads of nucleic acids in a test sample from said mammal, wherein said test sample comprises both nucleic acids from cancerous or precancerous cells and nucleic acids from constitutive cells, wherein the sequence reads are provided in an electronic format;
• (b) aligning, by the one or more processors, the at least 10,000 sequence reads to one or more reference sequences using a computing apparatus and thereby providing sequence tags corresponding to the sequence reads;
• (c) identifying, by the one or more processors, a number of sequence tags from the nucleic acids for one or more sequences of interest amplifications of which or deletions of which are known to be associated with cancers, wherein said sequences of interest are selected from chromosomes 1-22, X, and Y and segments thereof and identifying, by the one or more processors, a number of sequence tags for at least one normalizing sequence for each of the one or more sequences of interest;
• (d) calculating, by the one or more processors and using said number of sequence tags identified for each of said one or more sequences of interest and said number of sequence tags identified for each said normalizing sequence, a single sequence dose for each of said one or more sequences of interest,
• wherein the at least one normalizing sequence is a sequence that yields sequence doses for the 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;
• (e) evaluating said single sequence dose for each of said one or more sequences of interest, and thereby detecting aneuploidies or copy number variations in said sample;
• and
• (f) determining the presence of a cancer and/or an increased risk of a cancer based on the detected aneuploidies or copy number variations.