Bioinformatics (2018) doi: 10.1093/bioinformatics/bty247

Motivation: Network propagation has been widely used to aggregate and amplify the effects of tumor mutations using knowledge of molecular interaction networks. However, propagating mutations through interactions irrelevant to cancer leads to erosion of pathway signals and complicates the identification of cancer subtypes. Results: To address this problem we introduce a propagation algorithm, Network-Based Supervised Stratification (NBS2), which learns the mutated subnetworks underlying tumor subtypes using a supervised approach. Given an annotated molecular network and reference tumor mutation profiles for which subtypes have been predefined, NBS2 is trained by adjusting the weights on interaction features such that network propagation best recovers the provided subtypes. After training, weights are fixed such that mutation profiles of new tumors can be accurately classified. We evaluate NBS2 on breast and glioblastoma tumors, demonstrating that it outperforms the best network-based approaches in classifying tumors to known subtypes for these diseases. By interpreting the interaction weights, we highlight characteristic molecular pathways driving selected subtypes. Availability and implementation: The NBS2 package is freely available at: https://github.com/wzhang1984/NBSS. Supplementary information: Supplementary data are available at Bioinformatics online.

MOTIVATION: Although genome-wide association studies (GWAS) have found many common genetic variants associated with human diseases, it remains a challenge to elucidate the functional links between associated variants and complex traits. RESULTS: We developed a package called eResponseNet by implementing and extending the existing ResponseNet algorithm for prioritizing candidate disease genes through cellular pathways. Using type II diabetes (T2D) as a study case, we demonstrate that eResponseNet outperforms currently available approaches in prioritizing candidate disease genes. More importantly, the package is instrumental in revealing cellular pathways underlying disease-associated genetic variations. AVAILABILITY: The eResponseNet package is freely downloadable at http://hanlab.genetics.ac.cn/eResponseNet. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.