Systems and methods for genetic analysis of metastases

A method of determining phylogeny of a metastasis and treating a melanoma patient, the method comprising:

• obtaining a plurality of respective nucleic acid sequences from a primary tumor, a first metastasis, a second metastasis, and non-tumor tissue collected from a melanoma patient;
• informationally coupling an analysis engine to a sequence database, wherein the sequence database stores the plurality of respective nucleic acid sequences;
• determining, by the analysis engine, somatic single nucleotide variants (SSNVs) for the primary tumor, the first metastasis, and the second metastasis relative to the nucleic acid sequences from non-tumor tissue of the patient by using an error probability model,
• wherein the error probability model comprises the steps of mapping short reads of the tumor sequences to the reference genome and determining error probability by using a statistical model that incorporates the mapping qualities, error probabilities from raw sequence quality scores, sampling of two haplotypes, and an empirical model for correlated errors at a site;
• filtering, by the analysis engine, the determined SSNVs;
• determining, by the analysis engine, a status for each SSNV with respect to each of the nucleic acid sequences from the primary tumor, the first metastasis, and the second metastasis;
• using, by the analysis engine, the status to classify each SSNV into a class selected form the group consisting of as a fully shared SSNV, a partially shared SSNV, a private SSNV, or an absent SSNV;
• using, by the analysis engine, the classifications of the SSNVs, to calculate a phylogenetic profile for the primary tumor, the first metastasis, and the second metastasis;
• and
• generating a targeted therapy for the melanoma, prepared for administration, wherein the targeted therapy recognizes or binds to the fully shared SSNV, wherein the fully shared SSNV is one that is present in the primary tumor, first metastasis and second metastasis.