Performance evaluation with small cell lung cancer mutation data
To assess the capability of CaGe, we annotated genes from candidate mutations for a small cell lung cancer genome (SCLC) [12]. We had 59 genes with predicted functionally damaging mutations after applying 22,910 mutations to the PolyPhen and could annotate 22 previously reported known cancer genes successfully by applying the PolyPhen output for CaGe. Known cancer genes included RB1, which was mentioned as an SCLC-related gene in Pleasance's work; DST and ETS2, which were previously reported as SCLC-related genes but not mentioned in Pleasance's work; and 3 more genes (PDGFC, IL16, and AGTR2), which are known as lung cancer-related genes (Supplementary Table 1). The other 16 genes are known to be related to other cancer types, suggesting that they might be important in the carcinogenesis of SCLC as well. From the pathway analysis, we identified 12 known cancer genes and 11 genes in cancer-related pathways (Supplementary Table 2). Those 11 genes might also be important in the carcinogenesis of SCLC. Thus, we conclude that CaGe can annotate cancer genes effectively and suggest that CaGe will be useful in the identification of cancer-causing mutations and genes in HGT-based cancer genomics.
In this paper, we present a new cancer genomic tool, CaGe, for the assessment of candidate cancer genes having somatic mutations from HGT-based cancer genomics. CaGe provides users with information on cancer genes, mutations, pathways, and associated annotations through cancer gene annotation, cancer pathway annotation, cancer gene browsing, and cancer pathway browsing functions. It has a capacity to process SIFT or PolyPhen output files as direct input for usual NGS-based cancer genomics flows. Researchers can classify their candidate genes from cancer genome studies into previously known or novel categories of cancer genes and gain insight into the underlying carcinogenic mechanisms through a pathway analysis. We hope that CaGe will be useful for the identification of cancer-causing mutations and genes in HGT-based cancer genomics.