Systems and methods for predicting homologous recombination deficiency status of a specimen

A method of determining a homologous recombination pathway status of a cancer in a test subject, the method comprising:

• at a computer system having one or more processors, and memory storing one or more programs for execution by the one or more processors:
• (A) obtaining a first plurality of sequence reads, in electronic form, of a DNA sample from the test subject, the DNA sample comprising DNA molecules from a cancerous tissue of the subject;
• (B) obtaining a second plurality of sequence reads, in electronic, of an RNA sample from the test subject, the RNA sample comprising RNA molecules from the cancerous tissue of the subject;
• (C) determining, based on the first plurality of sequence reads, a first prediction for the homologous recombination pathway status of the cancerous tissue of the subject based on a measure of genome-wide loss of heterozygosity for the cancerous tissue of the subject;
• (D) determining, based on the second plurality of sequence reads, a second prediction for the homologous recombination pathway status of the cancerous tissue of the subject based on the expression levels of a plurality of genes in the cancerous tissue of the subject;
• (E) generating a subject data construct comprising (i) the first prediction for the homologous recombination pathway status of the cancerous tissue of the subject and (ii) the second prediction for the homologous recombination pathway status of the cancerous tissue of the subject;
• and
• (F) inputting the subject data construct into an ensemble model trained to distinguish between cancers with homologous recombination pathway deficiencies and cancers without homologous recombination pathway deficiencies, thereby determining the homologous recombination pathway status of the test subject.