Bocskei, Z. | Search bioRxiv

bioRxiv2020

COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms

We describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the Map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases and highlight new testable hypotheses.

systems biology↗

bioRxiv2020

A 3D human liver model of nonalcoholic steatohepatitis

AO_SCPLOWBSTRACTC_SCPLOWWe have developed an in vitro preclinical 3D Non-Alcoholic SteatoHepatitis (NASH) model by co-culturing four human primary liver cell types: hepatocytes, stellate, endothelial and Kupffer cells. Cells were embedded in a hydrogel of rat collagen in 96-well plate and a NASH-like environment was induced with a medium containing free fatty acids (FFAs) and tumor necrosis factor (TNF). This model was characterized by biochemical, imaging and transcriptomics analysis. On the one hand, we succeed in defining suitable culture conditions to maintain the 3D co-culture up to 10 days in vitro with the lowest level of steatosis, and reproducible low levels of inflammation and fibrosis. On the other hand, we induced NASH disease with a custom medium mimicking NASH features (hepatocyte injury, steatosis, inflammation and fibrosis). The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets. SO_SCPLOWUMMARYC_SCPLOWWe developed a 3D human liver model which exhibits many features of non-alcoholic steatohepatitis and that could become a platform for medium throughput drug screening.

cell biology↗