Mapping interindividual dynamics of innate immune response at single-cell resolution.
Mapping interindividual dynamics of innate immune response at single-cell resolution.
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DOI：
10.1038/s41588-023-01421-y
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发表时间：
2023-06
期刊：
影响因子：
30.8
通讯作者：
Teichmann, Sarah A.
中科院分区：
文献类型：
--
作者：
Kumasaka, Natsuhiko;Rostom, Raghd;Huang, Ni;Polanski, Krzysztof;Meyer, Kerstin B.;Patel, Sharad;Boyd, Rachel;Gomez, Celine;Barnett, Sam N.;Panousis, Nikolaos, I;Schwartzentruber, Jeremy;Ghoussaini, Maya;Lyons, Paul A.;Calero-Nieto, Fernando J.;Gottgens, Berthold;Barnes, Josephine L.;Worlock, Kaylee B.;Yoshida, Masahiro;Nikolic, Marko Z.;Stephenson, Emily;Reynolds, Gary;Haniffa, Muzlifah;Marioni, John C.;Stegle, Oliver;Hagai, Tzachi;Teichmann, Sarah A.
个体之间的常见遗传变异调节对病原体的细胞反应，并与多种免疫病理学有关，但它们如何动态改变感染后的反应尚不清楚。在这里，我们触发了来自68名健康供体的人成纤维细胞的抗病毒反应，并使用单细胞RNA测序分析了数万个细胞。我们开发了GASPACHO（GAuSsian Processes for Association mapping leveraging Cell Heterosis），这是一种统计方法，旨在识别细胞转录轨迹中的非线性动态遗传效应。该方法确定了1，275个表达数量性状基因座（局部错误发现率10%），这些基因座在应答过程中表现出来，其中许多与感染性和自身免疫性疾病的全基因组关联研究确定的易感基因座共定位，包括COVID-19易感基因座中的OAS 1剪接数量性状基因座。总之，我们的分析方法提供了一个独特的框架，用于描绘在单细胞分辨率下形成广泛的转录反应的遗传变异。GASPACHO是一种统计方法，使用单细胞RNA-seq数据识别非线性动态遗传效应。对人成纤维细胞中抗病毒反应的分析鉴定了1，275个表达QTL，其中许多与自身免疫性和感染性疾病的风险基因座共定位。
Common genetic variants across individuals modulate the cellular response to pathogens and are implicated in diverse immune pathologies, yet how they dynamically alter the response upon infection is not well understood. Here, we triggered antiviral responses in human fibroblasts from 68 healthy donors, and profiled tens of thousands of cells using single-cell RNA-sequencing. We developed GASPACHO (GAuSsian Processes for Association mapping leveraging Cell HeterOgeneity), a statistical approach designed to identify nonlinear dynamic genetic effects across transcriptional trajectories of cells. This approach identified 1,275 expression quantitative trait loci (local false discovery rate 10%) that manifested during the responses, many of which were colocalized with susceptibility loci identified by genome-wide association studies of infectious and autoimmune diseases, including the OAS1 splicing quantitative trait locus in a COVID-19 susceptibility locus. In summary, our analytical approach provides a unique framework for delineation of the genetic variants that shape a wide spectrum of transcriptional responses at single-cell resolution. GASPACHO is a statistical method that identifies nonlinear dynamic genetic effects using single-cell RNA-seq data. Analysis of an antiviral response in human fibroblasts identifies 1,275 expression QTLs, many of which colocalize with risk loci for autoimmune and infectious diseases.
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
OAS1处Sjögren综合征易感性基因座的鉴定，该基因座影响了同工型切换，蛋白质表达和对I型干扰素的反应性。
影响因子：
4.5
作者：
Li H;Reksten TR;Ice JA;Kelly JA;Adrianto I;Rasmussen A;Wang S;He B;Grundahl KM;Glenn SB;Miceli-Richard C;Bowman S;Lester S;Eriksson P;Eloranta ML;Brun JG;Gøransson LG;Harboe E;Guthridge JM;Kaufman KM;Kvarnström M;Cunninghame Graham DS;Patel K;Adler AJ;Farris AD;Brennan MT;Chodosh J;Gopalakrishnan R;Weisman MH;Venuturupalli S;Wallace DJ;Hefner KS;Houston GD;Huang AJW;Hughes PJ;Lewis DM;Radfar L;Vista ES;Edgar CE;Rohrer MD;Stone DU;Vyse TJ;Harley JB;Gaffney PM;James JA;Turner S;Alevizos I;Anaya JM;Rhodus NL;Segal BM;Montgomery CG;Scofield RH;Kovats S;Mariette X;Rönnblom L;Witte T;Rischmueller M;Wahren-Herlenius M;Omdal R;Jonsson R;Ng WF;for UK Primary Sjögren's Syndrome Registry;Nordmark G;Lessard CJ;Sivils KL
通讯作者：
Sivils KL
影响因子：
64.8
作者：
COVID-19 Host Genetics Initiative
通讯作者：
COVID-19 Host Genetics Initiative
影响因子：
64.8
作者：
Hagai T;Chen X;Miragaia RJ;Rostom R;Gomes T;Kunowska N;Henriksson J;Park JE;Proserpio V;Donati G;Bossini-Castillo L;Vieira Braga FA;Naamati G;Fletcher J;Stephenson E;Vegh P;Trynka G;Kondova I;Dennis M;Haniffa M;Nourmohammad A;Lässig M;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
56.9
作者：
Landry, Christian R.;Lemos, Bernardo;Hartl, Daniel L.
通讯作者：
Hartl, Daniel L.