BarkBase: Epigenomic Annotation of Canine Genomes

Abstract

Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly for complex diseases like cancer. Comprehensive genomic annotation of regulatory elements active in healthy canine tissues is crucial both for identifying candidate causal variants and for designing functional studies needed to translate genetic associations into disease insight. Currently, canine geneticists rely primarily on annotations of the human or mouse genome that have been remapped to dog, an approach that misses dog-specific features. Here, we describe BarkBase, a canine epigenomic resource available at barkbase.org. BarkBase hosts data for 27 adult tissue types, with biological replicates, and for one sample of up to five tissues sampled at each of four carefully staged embryonic time points. RNA sequencing is complemented with whole genome sequencing and with assay for transposase-accessible chromatin using sequencing (ATAC-seq), which identifies open chromatin regions. By including replicates, we can more confidently discern tissue-specific transcripts and assess differential gene expression between tissues and timepoints. By offering data in easy-to-use file formats, through a visual browser modeled on similar genomic resources for human, BarkBase introduces a powerful new resource to support comparative studies in dogs and humans.

Chromatin accessibility in canine stromal cells and its implications for canine somatic cell reprogramming

“…An astounding 84 Mb of canine transcribed sequence is not found in the existing Ensembl canine reference. In addition, one study reports finding most ATAC‐seq peaks in promoter areas, 76 whereas we found most peaks in distal intergenic areas. The inaccuracy of the genome annotation contributes to difficulty in assignment of genomic areas to appropriate genes or genomic functions.…”

Man’s best friend in life and death: scientific perspectives and challenges of dog brain banking

“…For example, the first canine epigenomics and transcriptomics database, BarkBase, was based on tissue samples obtained from five donated pet dogs [80] at the Cummings School of Veterinary Medicine, Tufts University, USA. Another research-centered biobank in Finland focuses on the investigation of rare canine diseases [62], supporting the notion that there is an increasing need for in-depth transcriptomics and epigenomic research in dogs, especially when they show specific conditions.…”

Epigenetic Mechanisms in Canine Cancer

“…Resources such as ENCODE (226), GTEx (227), Cancer Genome Atlas (TCGA) (https://www.cancer.gov/tcga) and NIH reference human epigenome (228), are constantly fueled with large numbers of information generated with next-generation bioinformatic tools and are extremely important for the elucidation of the most diverse diseases that affect humans and their therapeutic advances. With the same purpose, a~7 gigabytes genomic data platform, the BarkBase resource, has been recently developed (229). BarkBase contains data for 27 adult tissue types, with biological replicates, from five adult dogs, paired with 30x whole genome sequence data.…”