Data Resource Profile: Accessible Resource for Integrated Epigenomic Studies (ARIES)

Abstract

ARIES is a population-based resource of DNA methylation data accessible by the research community, established with the aim of improving our understanding of the determinants and consequences of epigenetic variation, in particular the role of DNA methylation in health and development. To this end, ARIES has profiled genome-wide DNA methylation on samples selected from approximately 1000 mother-child pairs at three time points in children and two time points in their mothers. ARIES has also profiled a wide range of fetal and adult tissues for reference purposes, with which to compare cord blood and peripheral blood DNA methylation patterns. A web portal has been constructed to allow openly accessible browsing of aggregate ARIES DNA methylation data in the context of other publicly available data on many aspects of gene function, using a custom-built data integration system (ARIES-Explorer). ARIES is a sub-study of the Avon Longitudinal Study of Parents and Children (ALSPAC).1,2 A sub-set of 1018 mother-offspring pairs were included in ARIES and were selected based on availability of DNA samples at two time- for the mother (at an antenatal clinic and at a follow-up clinic when their offspring were mean age 15.5 years) and three time points for the offspring [at birth, childhood, (mean age 7.5 years) and adolescence at mean age 15.5 years]. Figure 1 provides a schematic of the ALSPAC participants and time points profiled as part of ARIES. Schematic of the ALSPAC participants included in ARIES. A total of 1018 mother-child pairs have been profiled (v.1 data release 2014) at each of the five time points indicated, using the Illumina Infinium HumanMethylation450K BeadChip array. Ten of the same mother-child pairs have been profiled using whole-genome bisulphite sequencing at each of the five time points shown. GA, gestational age. ARIES children provided a DNA sample extracted from cord blood drawn from the umbilical cord upon delivery. A second DNA sample was extracted from peripheral blood drawn at the 7-year clinic visit, and a third at a clinic held either at age 15 or at age 17 years. Maternal samples were provided during the antenatal period [mean 25.7 (SD 9.5) weeks of gestation] and approximately 15–17 years later when mothers accompanied their child to a clinic visit or when they attended a clinic themselves. DNA methylation patterns differ between tissues. To generate a reference resource to facilitate comparison of peripheral blood DNA methylation with that of other tissues, we undertook profiling of DNA methylation from a range of other sources, where possible with paired peripheral blood DNA. Tissues were provided from three sources (as described below) for genome-wide DNA methylation profiling in ARIES using the Illumina Infinium HumanMethylation450 BeadChip (450 K) array. The tissues represented are summarized in Table 1 . Tissues profiled as part of ARIES in addition to cord blood and peripheral blood DNA samples from ALSPAC DNAm, DNA methylation data available; RNA, gene expression data available. Tissues profiled as part of ARIES in addition to cord blood and peripheral blood DNA samples from ALSPAC DNAm, DNA methylation data available; RNA, gene expression data available. Adult autopsy tissues. Twelve tissue types were harvested from 16 autopsy cases (10 male, 6 female) and provided for DNA methylation profiling and genotyping (through collaboration with Leiden University Medical Center). Tissue included peripheral blood (collected from the thoracic cavity) to allow cross-reference between blood and other tissue profiles from the same individuals. The samples were collected within 12 h of the death of the subjects with a mean age of 62.8 years. Further details can be found elsewhere.3 All samples are anonymized and procedures were performed according to the ethical guidelines in the Code for Proper Secondary Use of Human Tissue in The Netherlands (Dutch Federation of Medical Scientific Societies). Post-mortem brain tissues. Post-mortem brain tissue was provided by the Newcastle Brain Tissue Resource. A total of 20 samples underwent DNA methylation profiling from each of 10 male and 10 female donors. Multiple regions were sampled from post-mortem brain tissue; frontal cortex, temporal cortex, hippocampus, substantia nigra, dorsal raphe nucleus, putamen, hypothalamus, amygdala, cerebellum and peripheral blood DNA was also provided from the same individuals. Fetal tissues. Fetal tissues were provided by the MRC Human Developmental Biology Resource at Newcastle University from terminations of pregnancy. Twenty different tissues (listed in Table 1) were harvested from two male and two female fetuses of gestational age 12–14 weeks. No associated information is available for the fetal tissues (e.g. maternal age or reason for termination). Samples from 10 mother-child pairs selected from the ALSPAC cohort, that underwent Illumina 450 K array analysis at each of the available time points, were also whol