PhenoExam: gene set analyses through integration of different phenotype databases

Abstract

Background Gene set enrichment analysis (detecting phenotypic terms that emerge as significant in a set of genes) plays an important role in bioinformatics focused on diseases of genetic basis. To facilitate phenotype-oriented gene set analysis, we developed PhenoExam, a freely available R package for tool developers and a web interface for users, which performs: (1) phenotype and disease enrichment analysis on a gene set; (2) measures statistically significant phenotype similarities between gene sets and (3) detects significant differential phenotypes or disease terms across different databases. Results PhenoExam generates sensitive and accurate phenotype enrichment analyses. It is also effective in segregating gene sets or Mendelian diseases with very similar phenotypes. We tested the tool with two similar diseases (Parkinson and dystonia), to show phenotype-level similarities but also potentially interesting differences. Moreover, we used PhenoExam to validate computationally predicted new genes potentially associated with epilepsy. Conclusions We developed PhenoExam, a freely available R package and Web application, which performs phenotype enrichment and disease enrichment analysis on gene set G, measures statistically significant phenotype similarities between pairs of gene sets G and G′ and detects statistically significant exclusive phenotypes or disease terms, across different databases. We proved with simulations and real cases that it is useful to distinguish between gene sets or diseases with very similar phenotypes. Github R package URL is https://github.com/alexcis95/PhenoExam. Shiny App URL is https://alejandrocisterna.shinyapps.io/phenoexamweb/.

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“…To identify gene categories that were enriched we used the software SNP2GO, which annotates all SNPs with GO terms based on their proximity to genes, and therefore allows testing the enrichment for SNPs that affect particular GO terms. We used modified versions of the function snp2go, which allowed the testing of disease and tissue expression associated gene sets collected using the packages PhenoExam (version 0.1) 74 and RDAVIDWebService (version 1.28.0) 75 in R.…”