Accessible resource for integrated epigenomics studies (ARIES)

表观遗传学研究正成为国际上生物学研究的中心焦点。表观遗传学特征可作为暴露标记和预后或预测性生物标记物，白细胞甲基化目前是最常见的表观遗传修饰形式，在最容易获得的组织中，也是在许多研究中进行表观遗传分析的一种。在这种分析模式方面，雅芳父母及其子女纵向研究(ALSPAC)提供了独特的潜在资源，拥有两代人的数据和脐带血及后来的外周血样，考虑到宫内影响、代际传播、从出生到青春期前和青春期后甲基化的变化，并调查甲基化模式如何预测和随发育变化。这样的甲基化数据将与ALSPAC提供的广泛暴露、基因和表型数据相联系。人类数据将与记录白细胞和其他组织甲基化和基因表达之间关系的啮齿动物数据以及与营养过度、肥胖和老龄化有关的啮齿动物模型组织库结合在一起。额外的啮齿动物组织将根据要求储存起来，以供将来分析。产生的数据将被上传到专门为这项倡议开发的定制网络界面上供浏览，这将允许整合来自人类和啮齿动物来源的多个来源的数据。用户将可以访问数据探索实用程序、图形基因组浏览器和数据关系的交互式图形视图。将这一具有强烈特征的人类队列中的表观遗传学数据与啮齿动物表观遗传学和转录组数据相结合，以产生一个可利用的资源，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工作。我们将利用表观遗传学和基于人群的人类队列研究领域的领先科学家的专业知识来生成相关数据，并将这些数据与最新和高技能的生物信息学投入(由BBSRC先前的大量投资开发)结合起来，以实现我们宣布的目标。将拟议的生物数据生成与用于数据集成和访问的最先进的生物信息学工具结合在一起，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.