ABSTRACT
Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the 'Disease Module Identification DREAM Challenge', an open competition to comprehensively assess module identification methods across diverse protein-protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.
Subject(s)
Computational Biology/methods , Disease/genetics , Gene Regulatory Networks , Genome-Wide Association Study , Models, Biological , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Algorithms , Gene Expression Profiling , Humans , Phenotype , Protein Interaction MapsABSTRACT
SUMMARY: We define a disease module as a partition of a molecular network whose components are jointly associated with one or several diseases or risk factors thereof. Identification of such modules, across different types of networks, has great potential for elucidating disease mechanisms and establishing new powerful biomarkers. To this end, we launched the 'Disease Module Identification (DMI) DREAM Challenge', a community effort to build and evaluate unsupervised molecular network modularization algorithms. Here, we present MONET, a toolbox providing easy and unified access to the three top-performing methods from the DMI DREAM Challenge for the bioinformatics community. AVAILABILITY AND IMPLEMENTATION: MONET is a command line tool for Linux, based on Docker and Singularity containers; the core algorithms were written in R, Python, Ada and C++. It is freely available for download at https://github.com/BergmannLab/MONET.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.