Efficient representations of tumor diversity with paired DNA-RNA aberrations
Fig 1
Source-target pairs (STPs) are constructed using the links available in Reactome [19]. In the TCGA cancer cohorts, the mutation and copy number variation data are used to construct binary DNA aberration profiles; the presence of either a mutation or high/low copy number variation at a given gene is treated as an aberration for the given gene for that sample omics profile. The gene expression data are used to construct binary RNA aberration profiles based on falling outside the “normal” expression range (in quantiles) for each gene based on TCGA normal tissue expression data, as previously described [14]. The binary profiles are combined to produce paired DNA-RNA aberrations, following which filtering is performed by selecting pairs that are determined to be significant (two-sided χ2 test). The selected STPs then give rise to individual source (DNA) and target (RNA) aberrations, providing binary omics profiles at the level of source, target, and pairs. STPs that are present in less than 2% of samples for a given tissue are omitted. Then coverings are computed at the pair, source and target levels and subtype analysis and heterogeneity analysis carried out.