Description
TransFIC (TRANSformed Functional Impact for Cancer) is a method to transform Functional Impact scores taking into account the differences in basal tolerance to germline SNVs of genes that belong to different functional classes. This transformation allows to use the scores provided by well-known tools (e.g. SIFT, Polyphen2, MutationAssessor) to rank the functional impact of cancer somatic mutations. Mutations with greater transFIC are more likely to be cancer drivers.
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How does it perform?
TransFIC improves notably the performace of original scores on eight different datasets containing a set of positive mutations enriched in cancer drivers and a set of negative SNVs either enriched in cancer passengers or composed of polymorphisms (see Figure below)
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How does it work?
TransFIC takes as input the Functional Impact Score of a somatic mutation observed in cancer provided by one of the aforementioned tools. It then compares that score to the distribution of scores of germline SNVs observed in genes with similar functional annotations (for instance genes with the same molecular function as provided by the Gene Ontologies). The score is thus transformed using the Zscore formula. The result is that mutations in genes that are less tolerant to germline SNVs are amplified, while the scores of mutations on relatively tolerant genes are decreased.
How to obtain transFIC scores?
Currently, the easiest way to run transFIC to assess the functional impact of your cancer somatic mutations is using transFIC server, which implements the TransFIC of SIFT, Polyphen2 and MutationAssessor. Alternatively, it is possible to download a PERL script that computes transFIC for these same tools tools. While the webserver takes as input the genomic coordinates (hg19) and nucleotide change of the somatic mutation, the PERL script receives SIFT, PPH2 and MA scores to compute the corresponding TransFIC.
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