DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

A Graph-based Approach to Named Entity Categorization in Wikipedia using Conditional Random Fields

This paper presents a method for categorizing named entities in Wikipedia. In Wikipedia, an anchor text is glossed in a linked HTML text. We formalize named entity categorization as a task of categorizing anchor texts with linked HTML texts which glosses a named entity. Using this representation, we introduce a graph structure in which anchor texts are regarded as nodes. In order to incorporate HTML structure on the graph, three types of cliques are defined based on the HTML tree structure. We propose a method with Conditional Random Fields (CRFs) to categorize the nodes on the graph. Since the defined graph may include cycles, the exact inference of CRFs is computationally expensive. We introduce an approximate inference method using Treebased Reparameterization (TRP) to reduce computational cost. In experiments, our proposed model obtained significant improvements compare to baseline models that use Support Vector Machines

A pipeline approach for syntactic and semantic dependency parsing

This paper describes our system for syntactic and semantic dependency parsing to participate the shared task of CoNLL-2008. We use a pipeline approach, in which syntactic dependency parsing, word sense disambiguation, and semantic role labeling are performed separately: Syntactic dependency parsing is performed by a tournament model with a support vector machine; word sense disambiguation is performed by a nearest neighbour method in a compressed feature space by probabilistic latent semantic indexing; and semantic role labeling is performed by a an online passive-aggressive algorithm. The submitted result was 79.10 macroaverage F1 for the joint task, 87.18 % syntactic dependencies LAS, and 70.84 semantic dependencies F1. After the deadline, we constructed the other configuration, which achieved 80.89 F1 for the joint task, and 74.53 semantic dependencies F1. The result shows that the configuration of pipeline is a crucial issue in the task.