Annotation Search: the FAST Way

Περιέχει το πλήρες κείμενοThis paper discusses how annotations can be exploited to develop information access and retrieval algorithms that take them into account. The paper proposes a general framework for developing such algorithms that specifically deals with the problem of accessing and retrieving topical information from annotations and annotated documents

Manifesto of computational social science

The increasing integration of technology into our lives has created unprecedented volumes of data on society's everyday behaviour. Such data opens up exciting new opportunities to work towards a quantitative understanding of our complex social systems, within the realms of a new discipline known as Computational Social Science. Against a background of financial crises, riots and international epidemics, the urgent need for a greater comprehension of the complexity of our interconnected global society and an ability to apply such insights in policy decisions is clear. This manifesto outlines the objectives of this new scientific direction, considering the challenges involved in it, and the extensive impact on science, technology and society that the success of this endeavour is likely to bring about.The publication of this work was partially supported by the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement No. 284709, a Coordination and Support Action in the Information and Communication Technologies activity area (‘FuturICT’ FET Flagship Pilot Project). We are grateful to the anonymous reviewers for the insightful comments.Publicad

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

Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.

Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N-formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis