Accessible resource for integrated epigenomics studies (ARIES)

表观遗传学研究正在成为国际生物学研究的一个中心热点。表观遗传谱可以作为暴露标记和预后或预测性生物标记，白细胞甲基化目前是最常见的表观遗传修饰测量形式，在最容易获得的组织中，并且在许多研究中进行了表观遗传分析。关于这种分析模式，雅芳父母和他们的孩子纵向研究（ALSPAC）提供了一个独特的潜在资源，有两代人的数据和脐带血和后来的外周血样本，允许宫内影响，代际传递，从出生到青春期前和青春期后的甲基化变化，以及甲基化模式如何预测和随着发育而变化的调查。这些甲基化数据将与ALSPAC中广泛的暴露、基因型和表型数据联系起来。人类数据将与啮齿动物数据相结合，记录白细胞和其他组织甲基化和基因表达之间的关系，以及与营养过剩、肥胖和衰老相关的啮齿动物模型组织库。额外的啮齿动物组织将根据要求储存以供将来分析。生成的数据将上传，供在专门为此计划开发的基于web的定制界面上浏览，该界面将允许整合来自人类和啮齿动物的多个来源的数据。用户将能够访问数据探索工具、图形基因组浏览器和数据关系的交互式图形视图。将人类的表观遗传数据与啮齿类动物的表观遗传和转录组学数据相结合，产生一种可访问的资源，以加强表观遗传学领域的研究，造福于更广泛的科学界，这是一项相当大的生物信息学事业。我们将利用表观遗传学和基于人群的人类队列研究领域领先科学家的专业知识来生成相关数据，并将其与最新的高技能生物信息学输入（由BBSRC之前的大量投资开发）相结合，以实现我们既定的目标。总的来说，拟议的生物数据生成以及用于数据整合和访问的最先进的生物信息学工具将为表观遗传学研究提供明确的世界领先资源。

Epigenetic studies are becoming a central focus of biological research internationally. Epigenetic profiles can serve as exposure markers and as prognostic or predictive biomarkers, with leukocyte methylation currently being the most commonly measured form of epigenetic modification, in the most readily obtainable tissue and one that has undergone epigenetic analysis in many investigations. In regard to this mode of analysis the Avon Longitudinal Study of Parents and their Children (ALSPAC) provides a unique potential resource, in having two-generational data and cord blood and later peripheral blood samples available, allowing for intrauterine influences, intergenerational transmission, change in methylation from birth through to pre-pubertal and post-pubertal age, and investigation of how methylation patterns predict and change with development. Such methylation data would be linked to the extensive exposure, genotype and phenotype data available in ALSPAC. The human data will be coupled with rodent data documenting the relationship between leukocyte and other tissue methylation and gene expression and rodent model tissue banks related to over-nutrition, obesity and ageing. Additional rodent tissues will be banked for future analysis upon request. Data generated will be uploaded for browsing on a custom web-based interface developed specifically for this initiative which will permit the integration of data from multiple sources from both human and rodent sources. The user will have access to data exploration utilities, a graphical genome browser and interactive graphical views of data relationships. The integration of data on epigenetic profiles in this intensively characterised human cohort with rodent epigenetic and transcriptomic data to generate an accessible resource to enhance research in the field of epigenetics for the benefit of the wider scientific community represents a considerable bioinformatic undertaking. We will draw on the expertise of leading scientists in the field of epigenetics and population-based human cohort studies to generate relevant data and combine this with up to date and highly skilled bioinformatics input (developed with substantive previous investment from the BBSRC) to meet our stated objectives. In combination, the proposed generation of biological data together with state of the art bioinformatic tools for data integration and access, would provide an unequivocally world-leading resource for epigenetic studies.