PT  - JOURNAL ARTICLE
AU  - Nishant Thakur
AU  - Nathalie Pujol
AU  - Jacques van Helden
AU  - Robert H. Waterston
AU  - LaDeana W. Hillier
AU  - Laurent Tichit
AU  - Jonathan J. Ewbank
TI  - An integrated analysis tool reveals intrinsic biases in gene set enrichment
AID  - 10.1101/2021.07.12.452009
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.12.452009
4099  - http://biorxiv.org/content/early/2021/07/12/2021.07.12.452009.short
4100  - http://biorxiv.org/content/early/2021/07/12/2021.07.12.452009.full
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.