等質テスト構成における整数計画法を用いた最大クリーク探索の並列化

本論文では，等質テスト構成のための整数計画法を用いた最大クリークの並列化探索手法を提案する．等質テストとは各テストで出題される項目が異なるが，受験者得点の予測誤差が等質なテスト群である．等質テストでは同一能力の受験者が異なるテストを受験しても同一の得点となる保証があり，アイテムバンクから可能な限り多く生成することが望ましい．石井ら（2017）は等質テスト構成を最大クリーク問題と整数計画法により，従来手法より多くのテストを構成できる手法を提案した．本論文では，石井ら（2017）の手法で最も時間を要する整数計画法による逐次的頂点追加処理を並列化することを考える．具体的には，探索中のクリークの全頂点と隣接する頂点集合を候補頂点集合として，逐次的に整数計画法の解を追加し，要素数が一定となるまで並列化して繰り返し，この要素の最大クリークを追加することで探索を高速化できる．この提案手法の有効性は最大で従来手法で生成されるテスト数が194575個であったのに対し，438950個にテスト生成数を更新した．Educational assessments occasionally require uniform test forms for which each test form consists of a different set of items, but the forms meet uniform test specifications. For uniform test assembly, one of the most important issues is to incarease the number of assembled tests. Ishii et al. (2017) proposed using maximum clique problem and interger programming. The method assembled more uniform tests than traditional methods do. The proposal can be parallel searching vertices connected to all vertices in current clique. Ishii et al. (2017) method spend almost time for this process and impossible parallel algorithm, thus, the proposal can assemble a greater number of tests then the previous methods. As a result, the proposal assembled 438950 uniform tests as compared with 194575 uniform tests using the previous methods

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

等質テスト構成における整数計画法を用いた最大クリーク探索の並列化

本論文では，等質テスト構成のための整数計画法を用いた最大クリークの並列化探索手法を提案する．等質テストとは各テストで出題される項目が異なるが，受験者得点の予測誤差が等質なテスト群である．等質テストでは同一能力の受験者が異なるテストを受験しても同一の得点となる保証があり，アイテムバンクから可能な限り多く生成することが望ましい．石井ら（2017）は等質テスト構成を最大クリーク問題と整数計画法により，従来手法より多くのテストを構成できる手法を提案した．本論文では，石井ら（2017）の手法で最も時間を要する整数計画法による逐次的頂点追加処理を並列化することを考える．具体的には，探索中のクリークの全頂点と隣接する頂点集合を候補頂点集合として，逐次的に整数計画法の解を追加し，要素数が一定となるまで並列化して繰り返し，この要素の最大クリークを追加することで探索を高速化できる．この提案手法の有効性は最大で従来手法で生成されるテスト数が194575個であったのに対し，438950個にテスト生成数を更新した．Educational assessments occasionally require uniform test forms for which each test form consists of a different set of items, but the forms meet uniform test specifications. For uniform test assembly, one of the most important issues is to incarease the number of assembled tests. Ishii et al. (2017) proposed using maximum clique problem and interger programming. The method assembled more uniform tests than traditional methods do. The proposal can be parallel searching vertices connected to all vertices in current clique. Ishii et al. (2017) method spend almost time for this process and impossible parallel algorithm, thus, the proposal can assemble a greater number of tests then the previous methods. As a result, the proposal assembled 438950 uniform tests as compared with 194575 uniform tests using the previous methods