Open Targets Platform 22.09 has been released

Release Notes Oct 3, 2022

The latest release of the Platform — 22.09 — is now available at platform.opentargets.org.

Key points

New data, in particular:
New data integrity file, in line with FAIR principles

Key stats

Metric	Count
Targets	61,888
Diseases	20,931
Drugs	12,854
Evidence	14,229,684
Associations	7,003,171

Additional statistics are available on the Open Targets Community.

Additional data from our providers

Open Targets Genetics

We have integrated the data from the upcoming release of Open Targets Genetics — version 8. This includes new studies from the GWAS Catalog, the R6 FinnGen release, and sQTLs from GTEx.

Keep an eye out for more information when version 8 is released.

Genomics England PanelApp

We have integrated the latest update from Genomics England PanelApp, including 173 signed-off panels that relate to genomic tests listed in the NHS National Genomic Test Directory.

These panels contain only ‘Green’ genes, short tandem repeats and regions approved for diagnostic testing in England.

Gene burden

We have curated two studies published earlier this year for inclusion in our gene burden widget, an analysis of gene-level association tests using rare variant collapsing analyses.

If you would like to suggest other datasets for inclusion, please let us know on the Open Targets Community, or by commenting on this post!

Autism Spectrum Disorder (ASD)

Work from a research team at the Columbia University Medical Center, published earlier this year, brings in new evidence and novel targets linked to autism spectrum disorder.

The team analysed rare de novo and inherited coding variants from whole exome sequencing and whole genome sequencing data from over 40,000 autism cases, a majority which were provided by SPARK, and identified 60 genes associated with ASD, five of which had not previously been implicated in neurodevelopmental disorders.

“Overall, the genes we found may represent a different class of genes that are more directly associated with the core symptoms of ASD than previously discovered genes,” says Wendy Chung, MD, PhD, Kennedy Family Professor of Pediatrics and chief of clinical genetics in the Department of Pediatrics at the Columbia University Vagelos College of Physicians and Surgeons.

The gene burden widget shows one row for evidence associating NAV3 and autism spectrum disorder. — Gene burden widget for the association of NAV3 and autism spectrum disorder in the Open Targets Platform. This is a new association in the Platform, as NAV3 was one of the new genes shown to be implicated in ASD. NAV3 is thought to regulate cytoskeletal dynamics, and is associated with axon guidance and malignant growth and invasion.

Reference: Zhou X., Feliciano, P., Shu, C., Wang, T., Astrovskaya, I. et al. Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. Nat Genet 54, 1305-1319 (2022) (Open Access)

Body fat distribution

In an exome sequencing study of over 600,000 individuals across five ancestries, a team from the Regeneron Genetics Center identified 16 genes associated with fat distribution. The study included data from the UK Biobank, the Malmö Diet and Cancer Study, and the Mexico City Prospective Study.

Fat distribution, measured by the waist-to-hip ratio, is a major but overlooked risk factor for cardiovascular disease and diabetes, and drug development has mainly focused on obesity rather than fat distribution. Of the 16 genes the study linked to fat distribution, 4 have already been linked to BMI-adjusted waist-to-hip ratio, and one associated with BMI. The other 12 associations are new. Many of the genes are highly expressed in adipose tissue. The author also noted that association effects were often stronger in women than men.

Gene burden widgets INHBE associations with BMI-adjusted waist-hip ratio, which shows one row of data, and waist-hip ratio, which has two rows, one of which is from the Genebass study previously integrated in the Platform. — Associations of INHBE with BMI-adjusted waist-hip ratio — a new association — and waist-hip ratio in the Open Targets Platform. Gene burden evidence from Genebass and the AstraZeneca PheWas portal has previously linked INHBE to waist-hip ratio and birth weight. INHBE is a circulating growth factor from the activin family, which is highly and specifically expressed in hepatocytes, cells that make up 80% of the liver. Protein-truncating mutations in INHBE were associated with a lower waist to hip ratio, a favourable metabolic profile, and a lower risk of type 2 diabetes.

Reference. Akbari, P., Sosina, OA., Bovjin, J. et al. Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes. Nat Commun 13, 4844 (2022) (Open Access)

Probes and Drugs

We have pulled in data from Probes and Drugs’ July release (02.2022), which contains a number of updates and two new compound datasets from EuBOPEN and the JUMP-Cell painting consortium.

Additional information is available from their release notes.

Bringing the Platform in line with FAIR principles

Open Targets is working to align ourselves with the FAIR principles.

As part of this effort, we have made a data integrity file available in the data downloads release root folder. This is a complete listing of the files in the data release, with their corresponding SHA1 checksums.

This release also included a number of bug fixes and minor improvements. You can report any bugs or oddities on our Community forum: community.opentargets.org

Until the next release!