Array-based methods for analysing mixed samples using differently labelled allele-specific probes

A method for analyzing a mixed nucleic acid sample obtained from an organism, comprising:

• obtaining or deriving from the organism a nucleic acid sample containing a mixed nucleic acid population that includes a major subpopulation and a minor subpopulation, the major and minor subpopulations each including a plurality of target sequences each containing a polymorphic site, wherein the polymorphic site includes a bi-allelic SNP with a first nucleotide variant as a first allelic variant of the SNP (“A allele”) and a second nucleotide variant as a second allelic variant of the SNP (“B allele”);
• and
• genotyping the polymorphic sites, wherein the genotyping includes:
• (a) hybridizing at least a portion of the mixed nucleic acid population to an oligonucleotide probe of an oligonucleotide array;
• and
• (b) detecting from the oligonucleotide array, using a detector, a first signal indicating the presence or absence of the first nucleotide variant (“A signal”) and a second signal indicating the presence or absence of the second nucleotide variant (“B signal”);
• based on the genotyping, calculating a B-allele frequency (BAF) for one or more polymorphic sites for which the major subpopulation is homozygous;
• for each polymorphic site for which the major subpopulation is homozygous, determining whether the calculated BAF meets or exceeds a predetermined threshold;
• and
• selecting only those polymorphic sites for which the calculated BAF meets or exceeds the predetermined threshold for use in determining the fraction of the minor subpopulation;
• and
• determining the fraction of the minor subpopulation.