Network-based approaches for modeling disease regulation and progression

Molecular interaction networks lay the foundation for studying how biological functions are controlled by the complex interplay of genes and proteins. Investigating perturbed processes using biological networks has been instrumental in uncovering mechanisms that underlie complex disease phenotypes. Rapid advances in omics technologies have prompted the generation of high-throughput datasets, enabling large-scale, network-based analyses. Consequently, various modeling techniques, including network enrichment, differential network extraction, and network inference, have proven to be useful for gaining new mechanistic insights. We provide an overview of recent network-based methods and their core ideas to facilitate the discovery of disease modules or candidate mechanisms. Knowledge generated from these computational efforts will benefit biomedical research, especially drug development and precision medicine. We further discuss current challenges and provide perspectives in the field, highlighting the need for more integrative and dynamic network approaches to model disease development and progression

Inference of differential gene regulatory networks using boosted differential trees

Summary Diseases can be caused by molecular perturbations that induce specific changes in regulatory interactions and their coordinated expression, also referred to as network rewiring. However, the detection of complex changes in regulatory connections remains a challenging task and would benefit from the development of novel nonparametric approaches. We develop a new ensemble method called BoostDiff (boosted differential regression trees) to infer a differential network discriminating between two conditions. BoostDiff builds an adaptively boosted (AdaBoost) ensemble of differential trees with respect to a target condition. To build the differential trees, we propose differential variance improvement as a novel splitting criterion. Variable importance measures derived from the resulting models are used to reflect changes in gene expression predictability and to build the output differential networks. BoostDiff outperforms existing differential network methods on simulated data evaluated in four different complexity settings. We then demonstrate the power of our approach when applied to real transcriptomics data in COVID-19, Crohn's disease, breast cancer, prostate adenocarcinoma, and stress response in Bacillus subtilis. BoostDiff identifies context-specific networks that are enriched with genes of known disease-relevant pathways and complements standard differential expression analyses. Availability and implementation BoostDiff is available at https://github.com/scibiome/boostdiff_inference

Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing

Information developed to understand the molecular mechanisms of SARS-CoV-2 infection for predicting drug repurposing candidates is time-consuming to integrate and explore. Here, the authors develop an interactive online platform for virus-host interactome exploration and drug (target) identification