High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
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高通量表型分析揭示了免疫变异的广泛遗传和结构基础
DOI：
10.1101/688010
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Abeler-Dörner L
中科院分区：
文献类型：
--
作者：
Abeler-Dörner L
通过开发与高通量遗传筛查兼容的高密度小鼠免疫表型平台，我们已经确定了遗传学和结构对免疫变异的深刻贡献（http://www.immunophenotype.org）。具体来说，对 530 个独特的小鼠基因敲除进行高通量表型分析，鉴定出 140 个单基因“命中”，其中大多数以前没有免疫关联。此外，命中的基因集中富集在人类对功能丧失的耐受性较差的基因中。免疫表型平台还暴露了密集的相关网络，将免疫参数彼此联系起来并与特定的生理特征联系起来。这种联系限制了个体免疫参数的运动自由，从而强加了基因调节的“免疫结构”，其完整性与免疫能力相关。因此，我们为理解和监测健康和疾病的免疫变异提供了扩展的遗传资源和结构视角。
By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation (http://www.immunophenotype.org). Specifically, high-throughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic ‘hits’, of which most had no previous immunologic association. Furthermore, hits were collectively enriched in genes for which humans show poor tolerance to loss of function. The immunophenotyping platform also exposed dense correlation networks linking immune parameters with each other and with specific physiologic traits. Such linkages limit freedom of movement for individual immune parameters, thereby imposing genetically regulated ‘immunologic structures’, the integrity of which was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.
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影响因子：
30.8
作者：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A
影响因子：
4.8
作者：
Grasberger, Helmut;Refetoff, Samuel
通讯作者：
Refetoff, Samuel
影响因子：
27.4
作者：
Marquez, Ana;Vidal-Bralo, Laura;Martin, Javier
通讯作者：
Martin, Javier
影响因子：
64.8
作者：
Jackson, Ruaidhri;Kroehling, Lina;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
摘要 592：不同的细胞机制介导抗 CTLA-4 和抗 PD-1 检查点阻断
DOI：
--
发表时间：
2017
期刊：
影响因子：
--
作者：
S. Wei;Jacob H. Levine;D. Pe’er;J. Allison
通讯作者：
J. Allison