TOPAS, a network-based approach to detect disease modules in a top-down fashion.
NAR Genom Bioinform
; 4(4): lqac093, 2022 Dec.
Article
in En
| MEDLINE
| ID: mdl-36458021
ABSTRACT
A vast scenario of potential disease mechanisms and remedies is yet to be discovered. The field of Network Medicine has grown thanks to the massive amount of high-throughput data and the emerging evidence that disease-related proteins form 'disease modules'. Relying on prior disease knowledge, network-based disease module detection algorithms aim at connecting the list of known disease associated genes by exploiting interaction networks. Most existing methods extend disease modules by iteratively adding connector genes in a bottom-up fashion, while top-down approaches remain largely unexplored. We have created TOPAS, an iterative approach that aims at connecting the largest number of seed nodes in a top-down fashion through connectors that guarantee the highest flow of a Random Walk with Restart in a network of functional associations. We used a corpus of 382 manually selected functional gene sets to benchmark our algorithm against SCA, DIAMOnD, MaxLink and ROBUST across four interactomes. We demonstrate that TOPAS outperforms competing methods in terms of Seed Recovery Rate, Seed to Connector Ratio and consistency during module detection. We also show that TOPAS achieves competitive performance in terms of biological relevance of detected modules and scalability.
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
NAR Genom Bioinform
Year:
2022
Document type:
Article
Affiliation country: