Revealing the brain's molecular architecture.

Revealing the brain's molecular architecture.
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DOI：
10.1126/science.362.6420.1262
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发表时间：
2018-12
期刊：
Science
影响因子：
56.9
通讯作者：
A. Ashley-Koch;G. Crawford;M. Garrett;Lingyun Song;Alexias Safi;Graham D. Johnson;G. Wray;Timothy E. Reddy;F. Goes;Peter P. Zandi;J. Bryois;A. Jaffe;A. Price;N. A. Ivanov;L. Collado-Torres;Thomas M. Hyde;Emily E. Burke;Joel E. Kleiman;Ran Tao;J. Shin;S. Akbarian;Kiran Girdhar;Yanli Jiang;M. Kundakovic;Leanne Brown;Bibi S. Kassim;Royce B. Park;Jennifer R. Wiseman;Elizabeth Zharovsky;Rivka Jacobov;Olivia Devillers;E. Flatow;G. Hoffman;B. Lipska;David A. Lewis;V. Haroutunian;C. Hahn;A. Charney;S. Dracheva;A. Kozlenkov;Judson Belmont;Diane DelValle;Nancy J Francoeur;Evi Hadjimichael;D. Pinto;H. van Bakel;P. Roussos;J. Fullard;J. Bendl;M. Hauberg;L. Mangravite;M. Peters;Yooree Chae;Junming Peng;Mingming Niu;Xusheng Wang;M. J. Webster;T. Beach;Chao Chen;Yi Jiang;R. Dai;Annie W Shieh;Chunyu Liu;Kay S. Grennan;Yan Xia;R. Vadukapuram;Yongjun Wang;Dominic Fitzgerald;Lijun Cheng;Miguel A. Brown;Mimi Brown;Tonya M Brunetti;T. Goodman;Majd Alsayed;M. Gandal;D. Geschwind;H. Won;D. Polioudakis;Brie Wamsley;Jian-nan Yin;T. Hadzic;Luis de la Torre Ubieta;V. Swarup;Stephan J Sanders;M. State;Donna M. Werling;Joon-Yong An;B. Sheppard;A. Willsey;Kevin P. White;Mohana Ray;Gina Giase;A. Kefi;E. Mattei;Michael J. Purcaro;Z. Weng;Jill E. Moore;H. Pratt;Jack Huey;Tyler Borrman;P. Sullivan;P. Giusti-Rodríguez;Yunjung Kim;P. Sullivan;J. Szatkiewicz;S. Rhie;Christoper Armoskus;Adrian Camarena;P. Farnham;Valeria N. Spitsyna;Heather Witt;S. Schreiner;O. Evgrafov;J. A. Knowles;M. Gerstein;Shuang Liu;Daifeng Wang;Fábio C. P. Navarro;J. Warrell;Declan Clarke;Prashant S. Emani;Mengting Gu;Xueying Shi;Min Xu;Yucheng T. Yang;R. Kitchen;Gamze Gürsoy;Jing Zhang;Becky C. Carlyle;A. Nairn;Mingfeng Li;Sirisha Pochareddy;N. Šestan;Mario Škarica;Zhen Li;A. Sousa;G. Santpere;Jinmyung Choi;Yingying Zhu;Tianliuyun Gao;Daniel J. Miller;A. Cherskov;Mo Yang;Anahita Amiri;Gianfilippo Coppola;J. Mariani;S. Scuderi;A. Szekely;F. Vaccarino;Feinan Wu;S. Weissman;Tanmoy Roychowdhury;A. Abyzov
A. Ashley-Koch;G. Crawford;M. Garrett;Lingyun Song;Alexias Safi;Graham D. Johnson;G. Wray;Timothy E. Reddy;F. Goes;Peter P. Zandi;J. Bryois;A. Jaffe;A. Price;N. A. Ivanov;L. Collado-Torres;Thomas M. Hyde;Emily E. Burke;Joel E. Kleiman;Ran Tao;J. Shin;S. Akbarian;Kiran Girdhar;Yanli Jiang;M. Kundakovic;Leanne Brown;Bibi S. Kassim;Royce B. Park;Jennifer R. Wiseman;Elizabeth Zharovsky;Rivka Jacobov;Olivia Devillers;E. Flatow;G. Hoffman;B. Lipska;David A. Lewis;V. Haroutunian;C. Hahn;A. Charney;S. Dracheva;A. Kozlenkov;Judson Belmont;Diane DelValle;Nancy J Francoeur;Evi Hadjimichael;D. Pinto;H. van Bakel;P. Roussos;J. Fullard;J. Bendl;M. Hauberg;L. Mangravite;M. Peters;Yooree Chae;Junming Peng;Mingming Niu;Xusheng Wang;M. J. Webster;T. Beach;Chao Chen;Yi Jiang;R. Dai;Annie W Shieh;Chunyu Liu;Kay S. Grennan;Yan Xia;R. Vadukapuram;Yongjun Wang;Dominic Fitzgerald;Lijun Cheng;Miguel A. Brown;Mimi Brown;Tonya M Brunetti;T. Goodman;Majd Alsayed;M. Gandal;D. Geschwind;H. Won;D. Polioudakis;Brie Wamsley;Jian-nan Yin;T. Hadzic;Luis de la Torre Ubieta;V. Swarup;Stephan J Sanders;M. State;Donna M. Werling;Joon-Yong An;B. Sheppard;A. Willsey;Kevin P. White;Mohana Ray;Gina Giase;A. Kefi;E. Mattei;Michael J. Purcaro;Z. Weng;Jill E. Moore;H. Pratt;Jack Huey;Tyler Borrman;P. Sullivan;P. Giusti-Rodríguez;Yunjung Kim;P. Sullivan;J. Szatkiewicz;S. Rhie;Christoper Armoskus;Adrian Camarena;P. Farnham;Valeria N. Spitsyna;Heather Witt;S. Schreiner;O. Evgrafov;J. A. Knowles;M. Gerstein;Shuang Liu;Daifeng Wang;Fábio C. P. Navarro;J. Warrell;Declan Clarke;Prashant S. Emani;Mengting Gu;Xueying Shi;Min Xu;Yucheng T. Yang;R. Kitchen;Gamze Gürsoy;Jing Zhang;Becky C. Carlyle;A. Nairn;Mingfeng Li;Sirisha Pochareddy;N. Šestan;Mario Škarica;Zhen Li;A. Sousa;G. Santpere;Jinmyung Choi;Yingying Zhu;Tianliuyun Gao;Daniel J. Miller;A. Cherskov;Mo Yang;Anahita Amiri;Gianfilippo Coppola;J. Mariani;S. Scuderi;A. Szekely;F. Vaccarino;Feinan Wu;S. Weissman;Tanmoy Roychowdhury;A. Abyzov
中科院分区：
综合性期刊1区
文献类型：
--
作者：
A. Ashley-Koch;G. Crawford;M. Garrett;Lingyun Song;Alexias Safi;Graham D. Johnson;G. Wray;Timothy E. Reddy;F. Goes;Peter P. Zandi;J. Bryois;A. Jaffe;A. Price;N. A. Ivanov;L. Collado-Torres;Thomas M. Hyde;Emily E. Burke;Joel E. Kleiman;Ran Tao;J. Shin;S. Akbarian;Kiran Girdhar;Yanli Jiang;M. Kundakovic;Leanne Brown;Bibi S. Kassim;Royce B. Park;Jennifer R. Wiseman;Elizabeth Zharovsky;Rivka Jacobov;Olivia Devillers;E. Flatow;G. Hoffman;B. Lipska;David A. Lewis;V. Haroutunian;C. Hahn;A. Charney;S. Dracheva;A. Kozlenkov;Judson Belmont;Diane DelValle;Nancy J Francoeur;Evi Hadjimichael;D. Pinto;H. van Bakel;P. Roussos;J. Fullard;J. Bendl;M. Hauberg;L. Mangravite;M. Peters;Yooree Chae;Junming Peng;Mingming Niu;Xusheng Wang;M. J. Webster;T. Beach;Chao Chen;Yi Jiang;R. Dai;Annie W Shieh;Chunyu Liu;Kay S. Grennan;Yan Xia;R. Vadukapuram;Yongjun Wang;Dominic Fitzgerald;Lijun Cheng;Miguel A. Brown;Mimi Brown;Tonya M Brunetti;T. Goodman;Majd Alsayed;M. Gandal;D. Geschwind;H. Won;D. Polioudakis;Brie Wamsley;Jian-nan Yin;T. Hadzic;Luis de la Torre Ubieta;V. Swarup;Stephan J Sanders;M. State;Donna M. Werling;Joon-Yong An;B. Sheppard;A. Willsey;Kevin P. White;Mohana Ray;Gina Giase;A. Kefi;E. Mattei;Michael J. Purcaro;Z. Weng;Jill E. Moore;H. Pratt;Jack Huey;Tyler Borrman;P. Sullivan;P. Giusti-Rodríguez;Yunjung Kim;P. Sullivan;J. Szatkiewicz;S. Rhie;Christoper Armoskus;Adrian Camarena;P. Farnham;Valeria N. Spitsyna;Heather Witt;S. Schreiner;O. Evgrafov;J. A. Knowles;M. Gerstein;Shuang Liu;Daifeng Wang;Fábio C. P. Navarro;J. Warrell;Declan Clarke;Prashant S. Emani;Mengting Gu;Xueying Shi;Min Xu;Yucheng T. Yang;R. Kitchen;Gamze Gürsoy;Jing Zhang;Becky C. Carlyle;A. Nairn;Mingfeng Li;Sirisha Pochareddy;N. Šestan;Mario Škarica;Zhen Li;A. Sousa;G. Santpere;Jinmyung Choi;Yingying Zhu;Tianliuyun Gao;Daniel J. Miller;A. Cherskov;Mo Yang;Anahita Amiri;Gianfilippo Coppola;J. Mariani;S. Scuderi;A. Szekely;F. Vaccarino;Feinan Wu;S. Weissman;Tanmoy Roychowdhury;A. Abyzov

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大脑是我们最复杂的器官，它是认知和行为能力的根源，使我们作为一个物种独一无二，也是神经精神障碍易感性的基础。健康的大脑发育和神经功能依赖于转录组的精确时空调节，转录组因大脑区域和细胞类型而有很大差异。神经精神障碍遗传学的最新进展揭示了一种高度多基因的风险结构，包括影响小的多个常见变异和影响范围广泛的罕见变异。由于大多数遗传变异存在于基因组的非编码区，由于缺乏对人脑的调节和表观基因组图景的全面了解，建立变异和疾病表型之间的机械联系受到阻碍。为了解决这个问题，美国国家精神卫生研究所(NIMH)于2015年成立了心理编码联合会，以表征人类大脑中活跃的基因组元件的全谱，并阐明它们在发育、进化和神经精神障碍中的作用。为了实现这一目标，一个由15个研究机构组成的多学科研究团队通过分析成人死后的转录、表观基因组和基因组数据，以及在组织和单细胞水平上发育的人脑，生成了一份关于人脑的综合图谱。来自2000多个人的样本被表现为神经典型或被诊断为精神分裂症、自闭症谱系障碍(ASD)或双相情感障碍。
The brain, our most complex organ, is at the root of both the cognitive and behavioral repertoires that make us unique as a species and underlies susceptibility to neuropsychiatric disorders. Healthy brain develop-ment and neurological function rely on precise spatio-temporal regulation of the transcriptome, which varies substantially by brain region and cell type. Recent advances in the genetics of neuropsychiatric disorders reveal a highly polygenic risk architecture involving contributions of multiple common variants with small ef ects and rare variants with a range of ef ects. Because most of this genetic variation resides in noncoding regions of the genome, establishment of mechanistic links between variants and disease phenotypes is impeded by a lack of a comprehensive understanding of the regulatory and epigenomic landscape of the human brain.To address this matter, the PsychENCODE Consortium was established in 2015 by the National Institute of Mental Health (NIMH) to characterize the full spectrum of genomic elements active within the human brain and to elucidate their roles in development, evolution, and neuropsychiatric disorders. To reach this objective, a multidisciplinary team of investigators across 15 research institutes has generated an integrative atlas of the human brain by analyzing transcriptomic, epigenomic, and genomic data of postmortem adult and developing human brains at both the tissue and single-cell levels. Samples from more than 2000 individuals were phenotypically characterized as neurotypical or diagnosed with schizophrenia, autism spectrum disorder (ASD), or bipolar disorder.