Genotype Tissue Expression

Credit: National Human Genome Research Institute

The first Genotype Tissue Expression (GTEx) Project Community Meeting outside of the US took place 20-21st April with an international crowd gathering at the impressive PRBB overlooking the Barcelona seafront. If you’re unfamiliar with GTEx, it’s an NIH funded endeavour to establish a database and tissue bank that can be used by researchers worldwide to increase our understanding of how changes in our genes contribute to common human diseases. Broad Institute’s Kristin Ardlie kicked off the meeting with an update on the ambitious project which has now completed sample collection from 960 donors and is now quality controlling the final analysis and data release that will extend the RNA sequence data set to around 18-20,000 tissues. Whole exome and whole genome sequence data will also be available for all donors creating a unique public atlas of gene expression and regulation across multiple human tissues.

Over two days, an international roster showcased how the resource is already enabling studies of gene expression trait loci (eQTLs), and alternative splicing and enhancing the interpretation of GWAS and disease mechanisms. Machine learning approaches to associating histological phenotypes with gene expression and gene variants in populations were given by William Jones at the Sanger Institute and Barbara Engelhardt at Princeton. Landscaping of sex-differences provided a rich seam as expression differences were reported in thousands of genes in tissues common to both sexes pointing the way to understanding the molecular basis of human traits and disorders.

In the spirit of the need for integrated ’omics a morning was dedicated to exploring the power of GTEx data in connection with proteomic data to provide a window in to understanding human disease. The Human Protein Atlas uses integration of large data sets from different consortia and allows researchers to explore the localisation of all human proteins, tissues and organs. Cecilia Lindskog of Uppsala University’s talk highlighted how a unique combination of GTEx transcriptome data and proteomics provides the basis for pin pointing proteins to specific cells with special resolution for the identification of drug target candidates.

The meeting scratched the surface of how researchers are able to pose questions and start to deep dive the resource. Thrilling times lay ahead as studies like GTEx come to fruition, connect to other large scale projects and data sets such as ENCODE, GWAS, BluePrint and FANTOM, and set standards to guide efforts to build out richer biodata on specific tissues across multiple omics.

This instalment of the gatherings aimed to explore GTEx’s power to “enhance the use of human genomics for the benefit of all.” By giving so generously to the public the team really are laying the groundwork for establishing causal mechanisms at complex trait associated loci which have so far proved elusive.