Abstract

Complex traits including the genetic control of blood pressure have been associated with both coding and non-coding single nucleotide polymorphisms (SNPs) at more than a thousand loci across the human genome. Many of these haplotypes are found between and distant from genes, and their mechanisms leading to blood pressure variation are largely unknown. Attempts to compare and translate these non-coding mechanisms to animal model systems such as the laboratory rat are difficult, but even further complicated by the difficulty of accessing already existing large-scale genome-wide datasets including transcriptomic and epigenomic (e.g. chromatin accessibility, transcription factor binding, and DNA methylation) data that are currently distributed across a variety of public data repositories and supplementary datasets. These datasets are often annotated to previous and less complete reference genome assemblies, further hampering their broad use without time consuming reanalysis. Collectively, these challenges impede discovery and leveraging of these datasets across the broader research community toward understanding mechanisms controlling complex traits such as blood pressure. To address these challenges, the Rat ReMap Initiative seeks to establish a framework for a publicly accessible resource for rat genomic, transcriptomic and epigenomic data to housed within RGD, with analysis updated to the current reference genome assembly. Users will be able to explore and find these datasets, link to the original raw data, and access analyzed summary data files. Remapped datasets will be linked to existing genomic features, strain, and genetic variation annotations to link with disease, pathways, phenotypes, and models portals already annotated and maintained in the Rat Genome Database (RGD). Here we report our initial efforts to standardize metadata and remap a targeted set of publicly available rat transcriptome, chromatin accessibility and transcription factor binding datasets, some across multiple ages and both sexes, onto the newest rat reference assembly (mRatBN7.2), and to integrate them into an updated genome browser (JBrowse2) and into a comparative genome map browser (VCMap) at RGD.

Full Text
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