07/2020 - Drug mechanism‐of‐action discovery through the integration of pharmacological and CRISPR screens
Low success rates during drug development are due, in part, to the difficulty of defining drug mechanism‐of‐action and molecular markers of therapeutic activity. Here, we integrated 199,219 drug sensitivity measurements for 397 unique anti‐cancer drugs with genome‐wide CRISPR loss‐of‐function screens in 484 cell lines to systematically investigate cellular drug mechanism‐of‐action. We observed an enrichment for […]
07/2020 - A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). […]
07/2020 - Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA
Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin I and II and unveil the architecture of the human condensin II complex, revealing two putative DNA-entrapment sites. Using single-molecule imaging, we demonstrate that both […]
06/2020 - Connected from the Outside: The Role of US Regions in Promoting the Integration of the European Research System
Considerable efforts have been deployed by the European Union to create an integrated Research & Development area. In this paper, we focus on the structure and evolution of the European collaboration network as reflected by patent data. We study patent networks representing collaborations between inventors located in different geographic areas. Existing studies seem to indicate […]
06/2020 - O2S2 for the Geodata Deluge
We illustrate a fewrecent ideas of Object Oriented Spatial Statistics (O2S2), focusing on the problem of kriging prediction in situations where a global second order stationarity assumption for the random field generating the data is not justifiable or the space domain of the field is complex. By localizing the analysis through the Random Domain Decomposition […]