Methods and processes for non-invasive assessment of genetic variations

A method for reducing bias in sequence reads for a test sample comprising:

• (a) generating a relationship between (i) local genome bias estimates for sequence reads of a test sample and (ii) bias frequencies for the sequence reads of the test sample, thereby generating a sample bias relationship, wherein:
• the sequence reads are of circulating cell-free nucleic acid from the test sample, and
• the sequence reads are mapped to a reference genome;
• (b) comparing the sample bias relationship and a reference bias relationship, thereby generating a comparison, wherein,
• the reference bias relationship is between (i) local genome bias estimates for a reference and (ii) bias frequencies for the reference;
• and
• (c) normalizing counts of the sequence reads for the test sample according to the comparison generated in (b), whereby bias in the sequence reads for the test sample is reduced.