A key problem in systems biology is the discovery of regulatory mechanisms that drive phenotypic behaviour of complex biological systems in the form of multi-level networks. Modern multi-omics profiling techniques probe these fundamental regulatory networks but are often hampered by experimental restrictions leading to missing data or partially measured omics types for subsets of individuals due to cost restrictions. In such scenarios, in which missing data is present, classical computational approaches to infer regulatory networks are limited. In recent years, approaches have been proposed to infer sparse regression models in the presence of missing information. Nevertheless, these methods have not been adopted for regulatory network inference yet. In this study, we integrated regression-based methods that can handle missingness into KiMONo, a Knowledge guided Multi-Omics Network inference approach, and benchmarked their performance on commonly encountered missing data scenarios in single- and multi-omics studies. Overall, two-step approaches that explicitly handle missingness performed best for a wide range of random- and block-missingness scenarios on imbalanced omics-layers dimensions, while methods implicitly handling missingness performed best on balanced omics-layers dimensions. Our results show that robust multi-omics network inference in the presence of missing data with KiMONo is feasible and thus allows users to leverage available multi-omics data to its full extent.

MOTIVATION: Pathway annotation tools are indispensable for the interpretation of a wide range of experiments in life sciences. Network-based algorithms have recently been developed which are more sensitive than traditional overlap-based algorithms, but there is still a lack of good online tools for network-based pathway analysis. RESULTS: We present PathwAX II-a pathway analysis web tool based on network crosstalk analysis using the BinoX algorithm. It offers several new features compared with the first version, including interactive graphical network visualization of the crosstalk between a query gene set and an enriched pathway, and the addition of Reactome pathways. AVAILABILITY AND IMPLEMENTATION: PathwAX II is available at http://pathwax.sbc.su.se. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The vast amount of experimental data from recent advances in the field of high-throughput biology begs for integration into more complex data structures such as genome-wide functional association networks. Such networks have been used for elucidation of the interplay of intra-cellular molecules to make advances ranging from the basic science understanding of evolutionary processes to the more translational field of precision medicine. The allure of the field has resulted in rapid growth of the number of available network resources, each with unique attributes exploitable to answer different biological questions. Unfortunately, the high volume of network resources makes it impossible for the intended user to select an appropriate tool for their particular research question. The aim of this paper is to provide an overview of the underlying data and representative network resources as well as to mention methods of integration, allowing a customized approach to resource selection. Additionally, this report will provide a primer for researchers venturing into the field of network integration.