The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Reviewing Reports of Doctor\u27s Theses

電力系統の不平衡解析手法の開発に関する研究[藤原]Hybrid Particle Swarm Optimization for Flow Shop and Job Shop Scheduling Problems : フローショップ及びジョブショップスケジューリング問題におけるハイブリッド粒子群最適化[張]A Study on Anomaly-Based Countermeasures Against Malware Constructing Botnets : ボットネット構築マルウエアへの異常検知に基づく対策に関する研究[華]A Study on Security Analysis of Image Encryption Algorithms : 画像向け暗号方式の安全性解析に関する研究[趙]Development of Delta-Sigma Modulator for Broadband Wireless Communications : 広帯域無線通信のためのデルタ・シグマ変調器の開発[Ghazal]Development of Radio Frequency Ring Oscillators in Standard CMOS Technology : CMOS技術を用いたRFリング発振器の開発[Prapto]A Study on Key Disribution Schemes using Matched Filters for Wireless Communications : 整合フィルタを用いた無線通信に適した鍵配送方式に関する研究[西]CIRCUIT DESIGN AND IMPLEMENTATION FOR CARRIER SYNCHRONIZATION IN DIGITAL RECEIVERS : 搬送波同期のためのディジタル受信回路設計と実装[Mohamed]Algorithmic Aspects in Cloud Computing : クラウドコンピューティングのアルゴリズム的研究[趙]Studies on Online Multi-Stroke Character Recognition : オンラインマルチストローク文字の認識に関する研究[蔡]GISアプリケーションにおける景観表示の再現性を優先する空間データ処理方式に関する研究[久永]Study on Network Migration over Fairness Networks : 公平性のあるネットワーク上でのネットワーク移動に関する研究[Heru]Recognition of Human Actions using Visual Local Features : 局所特徴を用いた動画像中の人間動作認識[姫]Robust global localization using laser reflectivity : レーザ反射率を用いたロバストな大域的位置同定手法に関する研究[張]Dynamic Grasping and Manipulation of an Arbitrary Obkect by a Multi-Fingered Hand-Arm System : 多指ハンドアームシステムを用いた任意物体の動的把持および操作[河村]ディジタル制御技術を用いた太陽光発電システム用新方式最大電力点追従装置に関する研究 : New Maximum Power Point Trackers Using Digital Control Techniques in Photovoltaic Systems[Emad]Design and Analysis of Key Management and Authentication in Wireless Sensor Network and Vehicular Ad-hoc Network : 無線センサーネットワークと車両アドホックネットワークにおける鍵管理と認証方式の設計と解析[阮

学位論文審査報告

電力系統の不平衡解析手法の開発に関する研究[藤原] / Hybrid Particle Swarm Optimization for Flow Shop and Job Shop Scheduling Problems : フローショップ及びジョブショップスケジューリング問題におけるハイブリッド粒子群最適化[張] / A Study on Anomaly-Based Countermeasures Against Malware Constructing Botnets : ボットネット構築マルウエアへの異常検知に基づく対策に関する研究[華] / A Study on Security Analysis of Image Encryption Algorithms : 画像向け暗号方式の安全性解析に関する研究[趙] / Development of Delta-Sigma Modulator for Broadband Wireless Communications : 広帯域無線通信のためのデルタ・シグマ変調器の開発[Ghazal] / Development of Radio Frequency Ring Oscillators in Standard CMOS Technology : CMOS技術を用いたRFリング発振器の開発[Prapto] / A Study on Key Disribution Schemes using Matched Filters for Wireless Communications : 整合フィルタを用いた無線通信に適した鍵配送方式に関する研究[西] / CIRCUIT DESIGN AND IMPLEMENTATION FOR CARRIER SYNCHRONIZATION IN DIGITAL RECEIVERS : 搬送波同期のためのディジタル受信回路設計と実装[Mohamed] / Algorithmic Aspects in Cloud Computing : クラウドコンピューティングのアルゴリズム的研究[趙] / Studies on Online Multi-Stroke Character Recognition : オンラインマルチストローク文字の認識に関する研究[蔡] / GISアプリケーションにおける景観表示の再現性を優先する空間データ処理方式に関する研究[久永] / Study on Network Migration over Fairness Networks : 公平性のあるネットワーク上でのネットワーク移動に関する研究[Heru] / Recognition of Human Actions using Visual Local Features : 局所特徴を用いた動画像中の人間動作認識[姫] / Robust global localization using laser reflectivity : レーザ反射率を用いたロバストな大域的位置同定手法に関する研究[張] / Dynamic Grasping and Manipulation of an Arbitrary Obkect by a Multi-Fingered Hand-Arm System : 多指ハンドアームシステムを用いた任意物体の動的把持および操作[河村] / ディジタル制御技術を用いた太陽光発電システム用新方式最大電力点追従装置に関する研究 : New Maximum Power Point Trackers Using Digital Control Techniques in Photovoltaic Systems[Emad] / Design and Analysis of Key Management and Authentication in Wireless Sensor Network and Vehicular Ad-hoc Network : 無線センサーネットワークと車両アドホックネットワークにおける鍵管理と認証方式の設計と解析[阮