A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research

A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research
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DOI:
10.1038/sdata.2018.142
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发表时间:
2018-08-07
期刊:
影响因子:
9.8
通讯作者:
Bennett, David A.
Bennett, David A.
中科院分区:
综合性期刊2区
文献类型:
--
作者:
De Jager, Philip L.;Ma, Yiyi;Bennett, David A.

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我们从参加宗教秩序研究(ROS)或拉什记忆与衰老项目(MAP)的尸检个体中获得背外侧前额叶皮层的系统分析,这两个项目是联合设计的衰老和痴呆的前瞻性研究,包括生前详细的纵向认知表型和死后定量的结构化神经病理学检查。研究对象超过3322人。在这里,我们概述了第一代数据,包括全基因组基因型(n=2,090),全基因组测序(n=1,179), DNA甲基化(n=740),染色质免疫沉淀测序,使用抗组蛋白3赖氨酸9乙酰化(H3K9Ac)抗体(n=712), RNA测序(n=638)和miRNA谱(n=702)。其他组学数据的生成,包括ATACseq、蛋白质组学和代谢组学资料正在进行中。由于其前瞻性设计和招募老年人,非痴呆个体,这些数据可以重新用于调查大量综合征和定量神经科学表型。许多在死亡时认知未受损的受试者也提供了对老年未受损个体的人类大脑生物学的见解。
We initiated the systematic profiling of the dorsolateral prefrontal cortex obtained from a subset of autopsied individuals enrolled in the Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP), which are jointly designed prospective studies of aging and dementia with detailed, longitudinal cognitive phenotyping during life and a quantitative, structured neuropathologic examination after death. They include over 3,322 subjects. Here, we outline the first generation of data including genome-wide genotypes (n=2,090), whole genome sequencing (n=1,179), DNA methylation (n=740), chromatin immunoprecipitation with sequencing using an anti-Histone 3 Lysine 9 acetylation (H3K9Ac) antibody (n=712), RNA sequencing (n=638), and miRNA profile (n=702). Generation of other omic data including ATACseq, proteomic and metabolomics profiles is ongoing. Thanks to its prospective design and recruitment of older, non-demented individuals, these data can be repurposed to investigate a large number of syndromic and quantitative neuroscience phenotypes. The many subjects that are cognitively non-impaired at death also offer insights into the biology of the human brain in older non-impaired individuals.