Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy.
Deconvoluting complex correlates of COVID-19 severity with a multi-omic pandemic tracking strategy.
复制标题
DOI：
10.1038/s41467-022-32397-8
复制
发表时间：
2022-08-30
影响因子：
16.6
通讯作者：
Ashley, Euan A.
中科院分区：
文献类型：
--
作者：
Parikh, Victoria N.;Ioannidis, Alexander G.;Jimenez-Morales, David;Gorzynski, John E.;De Jong, Hannah N.;Liu, Xiran;Roque, Jonasel;Cepeda-Espinoza, Victoria P.;Osoegawa, Kazutoyo;Hughes, Chris;Sutton, Shirley C.;Youlton, Nathan;Joshi, Ruchi;Amar, David;Tanigawa, Yosuke;Russo, Douglas;Wong, Justin;Lauzon, Jessie T.;Edelson, Jacob;Montserrat, Daniel Mas;Kwon, Yongchan;Rubinacci, Simone;Delaneau, Olivier;Cappello, Lorenzo;Kim, Jaehee;Shoura, Massa J.;Raja, Archana N.;Watson, Nathaniel;Hammond, Nathan;Spiteri, Elizabeth;Mallempati, Kalyan C.;Montero-Martin, Gonzalo;Christle, Jeffrey;Kim, Jennifer;Kirillova, Anna;Seo, Kinya;Huang, Yong;Zhao, Chunli;Moreno-Grau, Sonia;Hershman, Steven G.;Dalton, Karen P.;Zhen, Jimmy;Kamm, Jack;Bhatt, Karan D.;Isakova, Alina;Morri, Maurizio;Ranganath, Thanmayi;Blish, Catherine A.;Rogers, Angela J.;Nadeau, Kari;Yang, Samuel;Blomkalns, Andra;O'Hara, Ruth;Neff, Norma F.;DeBoever, Christopher;Szalma, Sandor;Wheeler, Matthew T.;Gates, Christian M.;Farh, Kyle;Schroth, Gary P.;Febbo, Phil;DeSouza, Francis;Cornejo, Omar E.;Fernandez-Vina, Marcelo;Kistler, Amy;Palacios, Julia A.;Pinsky, Benjamin A.;Bustamante, Carlos D.;Rivas, Manuel A.;Ashley, Euan A.
SARS-CoV-2 大流行对不同种族和民族的人群产生了不同的影响。多组学方法是检查多祖先基因组风险的强大工具。我们利用流行病追踪策略，对 1049 名个体（736 名 SARS-CoV-2 阳性和 313 名 SARS-CoV-2 阴性）鼻咽拭子的病毒和宿主基因组和转录组进行测序，并将其与来自北加州不同流域的电子健康记录的数字表型相整合。通过混合图谱分解的全基因组关联揭示了新的与 COVID-19 严重程度相关的区域，其中包含先前报道的神经系统、肺部和病毒疾病易感性标记。对共有病毒基因组的系统动力学追踪显示与疾病严重程度或推断的祖先没有关联。多组学研究的总结数据揭示了宏基因组和 HLA 与重症 COVID-19 的关联。从残余鼻咽拭子中获得的大量数据与大规模自动提取的临床数据相结合，凸显了大流行追踪的强大策略，并揭示了高风险人群的独特的流行病学、遗传和生物学关联。重症 COVID-19 的风险存在遗传因素，但遗传效应很难与与遗传血统共变的社会结构区分开来。为了解决这个问题，作者利用混合图谱、病毒系统动力学以及宿主免疫和宏基因组测序来确定 COVID-19 严重程度的决定因素。
The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk. There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.
登录
查看更多内容
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
DOI：
10.1084/jem.20220028
发表时间：
2022-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng