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Updated: Jan 20, 2026

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Connectivity Significance for Disease Gene Prioritization in an Expanding Universe
Abstract:
A fundamental topic in network medicine is disease genes prioritization. The underlying hypothesis is that disease genes are organized as modules confined within the interactome. Here, we propose a novel algorithm called DiaBLE (DIAMOnD Background Local Expansion) which is a modified version of DIAMOnD, a successful algorithm based on the concept of connectivity significance. Instead of taking the whole interactome as the background model, DiaBLE considers as gene universe the smallest local expansion of the current seeds set at each iteration step. We show that DiaBLE significantly increases the overall DIAMOnD ranking quality of genes prioritization both in terms of cross-validation and biological consistency. Here, we focus on the two algorithms only since a comparative analysis among gene prioritization methods is beyond the scope of this study. Finally, we briefly discuss the improvement of biological insight provided by DiaBLE for two cancers (head and neck squamous cell carcinoma and kidney renal clear cell carcinoma).
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