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

A method of determining a homologous recombination pathway status of a cancerous tissue 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 plurality of at least 10,000 sequence reads, in electronic form, of an RNA sample from the test subject, the RNA sample comprising RNA molecules from the cancerous tissue of the test subject;
• (B) determining, based on the plurality of at least 10,000 sequence reads, a prediction for the homologous recombination pathway status of the cancerous tissue of the test subject based on the expression levels of a plurality of at least 30 genes in the cancerous tissue of the test subject using a model comprising a plurality of parameters, wherein values for the plurality of parameters have been defined by a set of labels comprising
• (i) a first label for HRD-positive status that corresponds to a genetic deficiency criterion selected from one or more genetic deficiency criteria, wherein the one or more genetic deficiency criteria comprises a first genetic deficiency criterion that is satisfied by a bi-allelic deficiency for a first gene associated with HRD-positive status, and
• (ii) a second label for HRD-negative status that corresponds to a set of one or more genetic sufficiency criteria, wherein the set of one or more genetic sufficiency criteria comprises a first genetic sufficiency criterion that is satisfied by bi-allelic wild type copies of the first gene, thereby determining the homologous recombination pathway status of the test subject.

A computer system comprising:

• one or more processors;
• and
• a non-transitory computer-readable medium including computer-executable instructions that, when executed by the one or more processors, cause the processors to perform a method for obtaining a homologous recombination pathway status of a cancer in a test subject, the method comprising:
• (A) obtaining a plurality of at least 10,000 sequence reads, in electronic, of an RNA sample from the test subject, the RNA sample comprising RNA molecules from the cancerous tissue of the test subject;
• (B) determining, based on the plurality of at least 10,000 sequence reads, a prediction for the homologous recombination pathway status of the cancerous tissue of the test subject based on the expression levels of a plurality of at least 30 genes in the cancerous tissue of the test subject using a model comprising a plurality of parameters, wherein values for the plurality of parameters have been defined by a set of labels comprising
• (i) a first label for HRD-positive status that corresponds to a genetic deficiency criterion selected from one or more genetic deficiency criteria, wherein the one or more genetic deficiency criteria comprises a first genetic deficiency criterion that is satisfied by a bi-allelic deficiency for a first gene associated with HRD-positive status, and
• (ii) a second label for HRD-negative status that corresponds to a set of one or more genetic sufficiency criteria, wherein the set of one or more genetic sufficiency criteria comprises a first genetic sufficiency criterion that is satisfied by bi-allelic wild type copies of the first gene,
• thereby determining the homologous recombination pathway status of the test subject.

A non-transitory computer-readable storage medium having stored thereon program code instructions that, when executed by a processor, cause the processor to perform a method for obtaining a homologous recombination pathway status of a cancer in a test subject, the method comprising:

• (A) obtaining a plurality of at least 10,000 sequence reads, in electronic, of an RNA sample from the test subject, the RNA sample comprising RNA molecules from the cancerous tissue of the test subject;
• (B) determining, based on the plurality of at least 10,000 sequence reads, a prediction for the homologous recombination pathway status of the cancerous tissue of the test subject based on the expression levels of a plurality of at least 30 genes in the cancerous tissue of the test subject using a model comprising a plurality of parameters, wherein values for the plurality of parameters have been defined by a set of labels comprising
• (i) a first label for HRD-positive status that corresponds to a genetic deficiency criterion selected from one or more genetic deficiency criteria, wherein the one or more genetic deficiency criteria comprises a first genetic deficiency criterion that is satisfied by a bi-allelic deficiency for a first gene associated with HRD-positive status, and
• (ii) a second label for HRD-negative status that corresponds to a set of one or more genetic sufficiency criteria, wherein the set of one or more genetic sufficiency criteria comprises a first genetic sufficiency criterion that is satisfied by bi-allelic wild type copies of the first,
• thereby determining the homologous recombination pathway status of the test subject.