Using a Network-Based Analysis Approach to Investigate the Involvement of in the Pathogenesis of Granulomatosis with Polyangiitis.

Chronic nasal carriage of (SA) has been shown to be significantly higher in GPA patients when compared to healthy subjects, as well as being associated with increased endonasal activity and disease relapse. The aim of this study was to investigate SA involvement in GPA by applying a network-based analysis (NBA) approach to publicly available nasal transcriptomic data. Using these data, our NBA pipeline generated a proteinase 3 (PR3) positive ANCA associated vasculitis (AAV) disease network integrating differentially expressed genes, dysregulated transcription factors (TFs), disease-specific genes derived from GWAS studies, drug-target and protein-protein interactions.

Quantitative Systems Pharmacology Approaches for Immuno-Oncology: Adding Virtual Patients to the Development Paradigm.

Drug development in oncology commonly exploits the tools of molecular biology to gain therapeutic benefit through reprograming of cellular responses. In immuno-oncology (IO) the aim is to direct the patient's own immune system to fight cancer. After remarkable successes of antibodies targeting PD1/PD-L1 and CTLA4 receptors in targeted patient populations, the focus of further development has shifted toward combination therapies.

Integration of Omics Data Sources to Inform Mechanistic Modeling of Immune-Oncology Therapies: A Tutorial for Clinical Pharmacologists.

Application of contemporary molecular biology techniques to clinical samples in oncology resulted in the accumulation of unprecedented experimental data. These "omics" data are mined for discovery of therapeutic target combinations and diagnostic biomarkers. It is less appreciated that omics resources could also revolutionize development of the mechanistic models informing clinical pharmacology quantitative decisions about dose amount, timing, and sequence.