MotivationSeveral molecular events are known to be cancer-related, including genomic aberrations, hypermethylation of gene promoter regions and differential expression of microRNAs. These aberration events are very heterogeneous across tumors and it is poorly understood how they affect the molecular makeup of the cell, including the transcriptome and proteome. Protein interaction networks can help decode the functional relationship between aberration events and changes in gene and protein expression.ResultsWe developed NetICS (Network-based Integration of Multi-omics Data), a new graph diffusion-based method for prioritizing cancer genes by integrating diverse molecular data types on a directed functional interaction network. NetICS prioritizes genes by their mediator effect, defined as the proximity of the gene to upstream aberration events and to downstream differentially expressed genes and proteins in an interaction network. Genes are prioritized for individual samples separately and integrated using a robust rank aggregation technique. NetICS provides a comprehensive computational framework that can aid in explaining the heterogeneity of aberration events by their functional convergence to common differentially expressed genes and proteins. We demonstrate NetICS’ competitive performance in predicting known cancer genes and in generating robust gene lists using TCGA data from five cancer types.Availability and implementationNetICS is available at https://github.com/cbg-ethz/netics.Supplementary information Supplementary data are available at Bioinformatics online.

High‐throughput DNA sequencing techniques enable large‐scale measurement of somatic mutations in tumors. Cancer genomics research aims at identifying all cancer‐related genes and solid interpretation of their contribution to cancer initiation and development. However, this venture is characterized by various challenges, such as the high number of neutral passenger mutations and the complexity of the biological networks affected by driver mutations. Based on biological pathway and network information, sophisticated computational methods have been developed to facilitate the detection of cancer driver mutations and pathways. They can be categorized into (1) methods using known pathways from public databases, (2) network‐based methods, and (3) methods learning cancer pathways de novo. Methods in the first two categories use and integrate different types of data, such as biological pathways, protein interaction networks, and gene expression measurements. The third category consists of de novo methods that detect combinatorial patterns of somatic mutations across tumor samples, such as mutual exclusivity and co‐occurrence. In this review, we discuss recent advances, current limitations, and future challenges of these approaches for detecting cancer genes and pathways. We also discuss the most important current resources of cancer‐related genes. WIREs Syst Biol Med 2017, 9:e1364. doi: 10.1002/wsbm.1364For further resources related to this article, please visit the WIREs website.

IMPORTANCE Surgery currently offers the only chance for a cure in pancreatic ductal adenocarcinoma (PDAC), but it carries a significant morbidity and mortality risk and results in varying oncologic outcomes. At present, to our knowledge, there are no tests available before surgical resection to identify tumors with an aggressive biological phenotype that could guide personalized treatment strategies. OBJECTIVE Identification of noninvasive genetic biomarkers that could direct therapy in patients whose cases are amenable to pancreatic cancer resection. DESIGN, SETTING, AND PARTICIPANTS This multicenter study combined a prospective European cohort of patients with PDAC who underwent pancreatic resection (from