Beyond Pathway Boundaries: A Degree-Aware Network Clustering Test for Gene Sets (opens in new tab)

Over-representation analysis (ORA) is the most commonly used interpretation tool for gene lists despite well-documented limitations: pathway boundaries are fixed, genes are assumed independent, and results depend on the background set. Network-based methods address these using interaction-network modularity, but introduce hub bias: highly connected genes appear clustered under naive nulls because curated networks overrepresent well-studied genes. Existing corrections are imperfect: edge permu...