Main areas: Cancer

OncodriveFM

Oncodrive-FM is an approach to uncover driver genes or gene modules. It computes a metric of functional impact using three well-known methods (SIFT, PolyPhen2 and MutationAssessor) and assesses how the functional impact of variants found in a gene across several tumor samples deviates from a null distribution. It is thus based on the assumption that any bias towards the accumulation of variants with high functional impact is an indication of positive selection and can thus be used to detect candidate driver genes or gene modules.

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####References

• Gonzalez-Perez A and Lopez-Bigas N. 2012. Functional impact bias reveals cancer drivers. Nucleic Acids Res., 10.1093/nar/gks743.

OncodriveClust

OncodriveCLUST is a method aimed to identify genes whose mutations are biased towards a large spatial clustering. This method is designed to exploit the feature that mutations in cancer genes, especially oncogenes, often cluster in particular positions of the protein. We consider this as a sign that mutations in these regions change the function of these proteins in a manner that provides an adaptive advantage to cancer cells and consequently are positively selected during clonal evolution of tumours, and this property can thus be used to nominate novel candidate driver genes.

The method does not assume that the baseline mutation probability is homogeneous across all gene positions but it creates a background model using silent mutations. Coding silent mutations are supposed to be under no positive selection and may reflect the baseline clustering of somatic mutations. Given recent evidences of non-random mutation processes along the genome, the assumption of homogenous mutation probabilities is likely an oversimplication introducing bias in the detection of meaningful events.

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####References

• Tamborero D, Gonzalez-Perez A and Lopez-Bigas N. OncodriveCLUST: exploiting the positional clustering of somatic mutations to identify cancer genes. Bioinformatics. 2013; doi: 10.1093/bioinformatics/btt395s