The dark side of enrichment analysis: Confusing term names, overlapping pathways, and study bias
Channel: Lars Juhl Jensen
Date: 11/10/2021

A look at the dark side of gene set enrichment analysis (GSEA). The presentation covers how the naming of high-level Gene Ontology terms can easily be misinterpreted by biologists, why seemingly irrelevant disease pathways often show up as significant, and how study bias can lead to artificially enriched terms. You may want to watch my short introduction to the core concepts of enrichment analysis first: https://youtu.be/2NC1QOXmc5o

0:00 Introduction: the dark side series, major problems that are rarely talked about, and gene set enrichment analysis.
0:22 Confusing term names: Gene Ontology enrichment, high-level terms with long names, misinterpretation of names, child terms, and the definition of metabolism
1:51 Overlapping pathways: pathway enrichment, surprising enrichment of disease pathways, and non-specific genes appearing in many pathways
2:42 Study bias: annotation bias towards disease genes and highly expressed genes, biases in users' gene lists, and the unfortunate consequences for functional enrichment
3:39 Not all bad: problems can be avoided by inspecting the genes that underlie enriched terms and using tools that correct for abundance bias

The aGOtool enrichment resource is available at https://agotool.org/