FarmGTEx TWAS-server: an interactive web server for customized TWAS analysis in both human and farm animals

Abstract

Transcriptome-wide association study (TWAS) is a powerful strategy for elucidating the molecular mechanisms behind the genetic loci of complex phenotypes. However, TWAS analysis is still daunting in many species due to the complication of the TWAS analysis pipeline, including the construction of the gene expression reference panel, gene expression prediction, and the subsequent association analysis in the large cohorts of genome-wide association study (GWAS). Farm animals are major protein sources and biomedical models for humans. To facilitate the translation of genetic findings across species, here we provide an interactive and easy-to-use multi-species TWAS web server for the entire community, called the FarmGTEx TWAS-server (http://twas.farmgtex.org), which is based on the GTEx and FarmGTEx projects. It includes gene expression data from 49, 34, and 23 tissues in 838 humans, 5,457 pigs, and 4,889 cattle, representing 38,180, 21,037, and 17,942 distinct eGenes in prediction models for humans, pigs, and cattle, respectively. It allows users to conduct gene expression prediction for any individuals with genotypes, GWAS summary statistics imputation, customized TWAS, and popular downstream functional annotation. It also provides 479,203, 1,208, and 657 tissue-gene-trait association trios for the research community, representing 1,129 human traits, 41 cattle traits, and 11 pig traits. In summary, the FarmGTEx TWAS-server is a one-stop solution for performing TWAS analysis for researchers without programming skills in both human and farm animal research communities. It will be maintained and updated timely within the FarmGTEx project to facilitate gene mapping and phenotype prediction within and across species.

Exploring the Interplay between the Hologenome and Complex Traits in Bovine and Porcine Animals Using Genome-Wide Association Analysis

“…To enhance the understanding of hologenome interactions in complex traits, we used GWA summary statistics to perform TWAS analysis and gene set enrichment analysis (GSEA) by using the FarmGTEx TWAS-server ( , accessed on 5 July 2023) [ 78 ]. Firstly, the GWAS imputation module imputed the SNPs from summary statistics according to eQTL mapping of cattle and pig reference genomes.…”

Integration of Selection Signatures and Protein Interactions Reveals NR6A1, PAPPA2, and PIK3C2B as the Promising Candidate Genes Underlying the Characteristics of Licha Black Pig

“…We obtained a variety of network categories, including co-expression, physical interaction, genetic interaction, shared protein domains, co-localization, pathway, and enriched genes in the network. (3) The Farm animal Genotype-Tissue Expression TWAS-Server (FarmGTEx TWAS-Server, , accessed on 12 December 2022) [ 27 ] provides the TPM (transcript per million) of numerous genes across pig tissues. The TPM data were used to evaluate the correlation of gene expression between NR6A1 , PAPPA2 , PIK3C2B , and FASN in different pig tissues.…”

Molecular Design-Based Breeding: A Kinship Index-Based Selection Method for Complex Traits in Small Livestock Populations

“…The effectiveness of the kinship index based selection (KIS) method is limited by the accuracy and coverage of functional genes in pigs. Previous studies have reported on the association of functional genes with traits in pigs, and databases, such as The Farm animal Genotype-Tissue Expression TWAS server ( ) [ 18 ] and PigVar [ 19 ], exist which combine non-redundant variations and evolutionary selective scores. Results from the simulation study indicated that the mating method used may impact selection by the KIS method and that the truncated selection method used may not be the most optimal.…”