Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Rule-based inspection of printed green ceramic tape

A template-based vision system for the 100% inspection of printed flaws on green ceramic tape has been developed. Design goals included a requirement for the detection of flaws as small as two thousandths of an inch on parts up to 8 by 8 inches in size. The inspection engine is a Datacube, Inc., MV200 pipeline processor. As each part is inspected, four 2K by 2K pixel quadrant images are stitched together to construct a single 4K by 4K pixel image with the aid of multiple fiducials located in each quadrant. The part fiducial locations, mask image, and punched-hole position data are generated, beforehand, from CAD designs using a defect map editor (DME), a preprocessing software package developed for the PC. The DME also generates a part ``defect map``. Each unique structure in the printed pattern is defined as an object. Objects are grouped into user-defined categories such as die pads, contact fingers, traces, and electrolysis buses. The map is used during the runtime inspection to associate each detected defect with an object group and a particular defect specification for that group. Repeat defects are optionally tracked for up to three consecutive parts