PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs

Abstract

To fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.

Graphical Abstract

Figure 1.

Schematic overview of the PigBiobank. It consists of six components. (i) Trait: 264 complex pig traits derived from six main trait categories. (ii) Resource: data collected from multiple relevant international projects. (iii) Biology: biological elucidation using multi-omics data, multi-methods analysis, and cross-species comparison. (iv) Analysis: seven online analysis modules/tools are available in the PigBiobank web portal. (v) Search: users can query the database in four different ways (by trait, gene, variant, or region) in a user-friendly manner. (vi) Download: data files or results are available for free download.

Figure 2.

The web interface of the PigBiobank. (A) Query entries for the PigBiobank database. The menu options 'Home', ‘Trait Browser’, and ‘Module’ provide access to the quick search, detailed trait browses, and online analysis modules, respectively. (B) Query visualization. A total of six sections namely ‘Summary-based Analysis’, ‘Content of Region’, ‘Integrative Analysis’, ‘Enrichment Analysis’, ‘Cross-species Analysis’, and ‘Associated Variants/Genes’ are presented in the database.

Figure 3.

Case study of trait search module (MetaGWAS_M_BFT). (A) The summary information of the study. (B) The manhatton plot of variant-based and gene-based GWAS, and the list of traits significantly genetic correlated (P< 0.05) with study. (C) The scatter plot of significant associations of TWAS, and SMR (corrected P< 0.05). (D) The bar plot and heatmap show significant results of enrichment analysis for study, containing the variant enrichment trait-relevant functional elements, variant enrichment of trait-relevant tissue, heritability enrichment of trait-relevant tissue, and variant enrichment of trait-relevant tissue-chromatin states (P< 0.05). (E) The heatmap of human traits significantly correlated with pig study based on TWAS (P< 0.05).

Figure 4.

Case study of region search (SSC7: 97136980∼97910694), variant search (rs333375257), and gene search (ABCD4). (A) The result of the region search, including the summary information of the target region, the genomics viewer of the region and the list of significant variants in GWAS within the target region, or genes overlapped within the target region. (B) The result of the variant search, containing the summary information of the target variant, the genomics viewer of the region (bp ±500 kb), and the scatter plot of SNP-based PheWAS and the list of associated genes based on physical location (±500 kb), or molecular QTL mapping from top to down, respectively. (C) The result of the gene search, containing the summary information of the target gene, gene-based PheWAS, the genomics viewer of the region around the gene (gene body ±200 kb), and scatter plot of significant TWAS in eQTL, eeQTL and sQTL.