Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrate multiomics data pertaining to lung epithelial cells-specific co-expression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity that may foster effective therapeutic design. Funding: This work was supported by the National Science Foundation (IOS-1557796) to M.S.M., and U54 ES 030246 from NIH/NIEHS to M. A. Conflict of Interest: The authors declare no competing interests. The authors also declare no financial interests.

Network biology to uncover functional and structural properties of the plant immune system.

In the last two decades, advances in network science have facilitated the discovery of important systems' entities in diverse biological networks. This graph-based technique has revealed numerous emergent properties of a system that enable us to understand several complex biological processes including plant immune systems. With the accumulation of multiomics data sets, the comprehensive understanding of plant-pathogen interactions can be achieved through the analyses and efficacious integration of multidimensional qualitative and quantitative relationships among the components of hosts and their microbes. This review highlights comparative network topology analyses in plant-pathogen co-expression networks and interactomes, outlines dynamic network modeling for cell-specific immune regulatory networks, and discusses the new frontiers of single-cell sequencing as well as multiomics data integration that are necessary for unraveling the intricacies of plant immune systems.

Epigenetic regulation in the pathogenesis of non-melanoma skin cancer.

Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis.

COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrate multiomics data pertaining to lung epithelial cells-specific co-expression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity that may foster effective therapeutic design. Funding: This work was supported by the National Science Foundation (IOS-1557796) to M.S.M., and U54 ES 030246 from NIH/NIEHS to M. A. Conflict of Interest: The authors declare no competing interests. The authors also declare no financial interests.