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

Treatment of anaerobic digested effluent in biochar-packed vertical flow constructed wetland columns: role of media and tidal operation

Abstract. As more data-intensive applications emerge, advanced retrieval semantics, such as ranking or skylines, have attracted attention. Geographic information systems are such an application with massive spatial data. Our goal is to efficiently support skyline queries over massive spatial data. To achieve this goal, we first observe that the best known algorithm VS 2, despite its claim, may fail to deliver correct results. In contrast, we present a simple and efficient algorithm that computes the correct results. To validate the effectiveness and efficiency of our algorithm, we provide an extensive empirical comparison of our algorithm and VS 2 in several aspects.

Inference of Finite-State Transducers By Using Regular Grammars and Morphisms

A technique to infer finite-state transducers is proposed in this work. This technique is based on the formal relations between finite-state transducers and regular grammars. The technique consists of: 1) building a corpus of training strings from the corpus of training pairs; 2) inferring a regular grammar and 3) transforming the grammar into a finite-state transducer