Enrichment on steps, not genes, improves inference of differentially expressed pathways.

ABSTRACT: Enrichment analysis is frequently used in combination with differential expression data to investigate potential commonalities amongst lists of genes and generate hypotheses for further experiments. However, current enrichment analysis approaches on pathways ignore the functional relationships between genes in a pathway, particularly OR logic that occurs when a set of proteins can each individually perform the same step in a pathway. As a result, these approaches miss pathways with large or multiple sets because of an inflation of pathway size (when measured as the total gene count) relative to the number of steps. We address this problem by enriching on step-enabling entities in pathways. We treat sets of protein-coding genes as single entities, and we also weight sets to account for the

SUBMITTER: Markarian N 

PROVIDER: S-EPMC10994554 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature