Context-Specific Tumor-Only Mutation Classification

A method for context-specific mutation classification, comprising:

• receiving a sequencing alignment for a tumor sample, the sequencing alignment comprising a plurality of sequencing reads aligned to a reference sequence;
• identifying a mutation at a genetic region where at least a subset of the plurality of sequencing reads differs from the reference sequence;
• classifying the mutation as germline or somatic based on a log likelihood ratio relative to a threshold, the log likelihood ratio indicating a relative fit of a germline mutation model of the mutation and a somatic mutation model of the mutation to data from the sequencing alignment based on a context of the mutation;
• and
• outputting the classification of the mutation.

A method for context-specific mutation classification, comprising:

• receiving sequencing alignments for a plurality of tumor samples obtained from an individual, the sequencing alignments comprising a plurality of sequencing reads aligned to a reference sequence for individual tumor samples of the plurality of tumor samples;
• identifying a mutation at a genetic region where at least a subset of the plurality of sequencing reads differs from the reference sequence for the plurality of tumor samples;
• separately calculating log likelihood ratio distributions for individual samples of the plurality of tumor samples, each log likelihood ratio distribution indicating a relative fit of a germline model of the mutation and a somatic model of the mutation to data from a corresponding sequencing alignment;
• classifying the mutation as germline or somatic based on a joint log likelihood ratio for the plurality of tumor samples relative to a joint threshold, the joint log likelihood ratio being a sum of the log likelihood ratio distributions of the individual samples;
• and
• outputting the classification of the mutation.