RT Journal Article SR Electronic T1 An integrated analysis tool reveals intrinsic biases in gene set enrichment JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.12.452009 DO 10.1101/2021.07.12.452009 A1 Nishant Thakur A1 Nathalie Pujol A1 Jacques van Helden A1 Robert H. Waterston A1 LaDeana W. Hillier A1 Laurent Tichit A1 Jonathan J. Ewbank YR 2021 UL http://biorxiv.org/content/early/2021/07/12/2021.07.12.452009.abstract AB Generating meaningful interpretations of gene lists remains a challenge for all large-scale studies. Many approaches exist, often based on evaluating gene enrichment among pre-determined gene classes. Here, we conceived and implemented yet another analysis tool (YAAT), specifically for data from the widely-used model organism C. elegans. YAAT extends standard enrichment analyses, using a combination of co-expression data and profiles of phylogenetic conservation, to identify groups of functionally-related genes. It additionally allows class clustering, providing inference of functional links between groups of genes. We give examples of the utility of YAAT for uncovering unsuspected links between genes and show how the approach can be used to prioritise genes for in-depth study. Our analyses revealed several limitations to the meaningful interpretation of gene lists, specifically related to data sources and the “universe” of gene lists used. We hope that YAAT will represent a model for integrated analysis that could be useful for large-scale exploration of biological function in other species.Competing Interest StatementThe authors have declared no competing interest.