Network Propagation as a Tool for Deciphering Disease Mechanisms
summary
Per-sample binary mutation and differential-expression calls are propagated across a 150,000‑edge HIPPI network (random walk with restart) to create propagated matrices; logistic regression on features like mean, variance and the minimum propagation score boosts AUC by ~0.2 for breast cancer and glioblastoma when recovering pathway genes and yields survival‑significant top hits. A second pipeline computes empirical p‑values against random priors, then applies ILP optimal clustering to find disease modules; on ~100 diseases (≈8,000 associations) the method produces ≈50% enriched clusters versus 36% (PRINCE) and 30% (HotNet2); a Cytoscape app Propagate is provided.
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chapters (20)
- 0:00Network propagation as a tool for deciphering disease mechanisms
- 0:40Guilt by association
- 2:29The propagation score function
- 2:59Propagation in network biology
- 3:27Outline
- 3:57Motivation
- 5:54The effect of propagation (BRCA)
- 9:13The computational workflow
- 10:09Performance evaluation
- 10:49Mutations vs. expression
- 15:50Summary (part I)
- 23:40Associating diseases with complexes
- 24:43The general workflow
- 26:14Statistical scoring
- 27:32Finding dense clusters
- 29:00Data sets
- 30:35external validation
- 31:59using information from similar diseases
- 33:12Case analysis - epilepsy syndrome
- 34:01Summary (part II)
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