9 research outputs found

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

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    「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

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    「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

    Numerical Analysis of Anaerobically Digested Slurry with Irrigation Water in Rice Paddy

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    The objective of this study was to analyze the two–dimensional spatial and temporal distribution of anaerobically digested slurry in rice paddy fields. For this investigation, MIKE 21 HD (MI) was used, and advection and diffusion were taken into consideration. To verify the model for rice paddy fields, a field observation was conducted at a lysimeter, where anaerobically digested slurry was mixed with irrigation water and the fluctuations of T–N at five points were measured. Though some factors, such as undulations on the soil surface, created discrepancies between anticipated and actual values, the overall calculations agreed with the measurements, indicating that the model was fairly adaptable. To estimate the uniformity of distribution of anaerobically digested slurry, the spatial and temporal distribution of T–N at the lysimeter was simulated with MI. The results indicated that T–N was not distributed evenly with low level T–N around the water inlet. To determine a method that would effectively distribute anaerobically digested slurry, a scenario with a trench and two inlets was simulated. Trenches 3.00×10–2m deep and 6.17×10–2m wide were installed longitudinally among the rice plants. In addition, both lateral and longitudinal inlets were introduced. The water from the inlet in the x–direction was faster than that in the y–direction. In this scenario, the blocks on the levee were removed, and T–N from both inlets was fixed in the entire simulation period. Also, T–N level was fixed the entire time, assuming that anaerobically digested slurry was continuously mixed with the irrigation water. The results revealed uniform distribution of anaerobically digested slurry in terms of T–N in 50 minutes, indicating that those introductions effectively distributed anaerobically digested slurry in a rice paddy

    A checklist of the bats of Peninsular Malaysia and progress towards a DNA barcode reference library

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

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