15 April 2025
Boehringer Ingelheim scientists have analysed and published on the impact of structural variants (SVs) on traits related to respiratory, cardiometabolic and liver dieseases. Now we make key data of that study1 available through the opnMe portal to allow unrestricted access by researchers to advance knowledge of genetic variation in the human population.
Establishing an association between a specific genetic modification and a defined disease phenotype represents an important step in the discovery of new drug targets. Drug target identification takes a lot of effort and requires many costly and time-consuming experiments. Hence, integrating computational methods and analyses of large-data population biobanks into target identification can significantly accelerate the discovery research process towards novel treatments for patients.
Researchers at Boehringer Ingelheim now have created a new “genomic lens” that helps scientists to speed up drug discovery at lower costs. For example, long-read sequencing of all participants in the UK Biobank would cost around $0.5bn (USD). The novelty of their approach is the incorporation of SVs into genome-wide association analyses (GWAS). Rather than sequencing whole genomes of participants of cohort studies, they sequenced a limited number of individuals to establish a high-quality SV reference panel. 888 individuals of different ancestries including Europeans, Americans, East Asians, South Asians, and Africans from the 1000 Genomes Project were sequenced with the Oxford Nanopore long-read platform that facilitates detection of SVs.
The team demonstrated the utility of the SV reference panel by imputing SVs into the approximately 500,000 participants of the UK Biobank and conducting GWASs on 32 disease-relevant phenotypes related to respiratory, cardiometabolic and liver diseases, in addition to 1,463 protein levels. A significant portion of the SVs that showed associations with traits or protein levels were found to be novel, meaning they were not previously identified in the short-read sequencing of the 1000 Genomes Project. With their studies, the researchers were able to identify causal genes at hundreds of associated loci with relevance to respiratory diseases, as highlighted with selected examples.
The imputation panel is designed to analyze structural variants (SVs) that intersect with important genetic regions such as exons, splice-sites, promoters, or enhancers of protein-coding genes at loci associated with GWAS. Therefore, this panel has the potential to be incorporated into the standard process of prioritizing genes after conducting GWAS, and additionally, it can be used in various ways to integrate SV data with other omics data, particularly in machine learning-based frameworks. For instance, the genomic features derived from genome-wide SV analysis could be utilized in models for high-throughput gene prioritization following GWAS, disease subtyping and precision medicine, as well as predicting drug response and adverse events.
To facilitate wider impact of this well-characterized imputation panel generated from the Genomic Lens project, the underlying data have been made available exclusively via the opnMe portal.
Significance of this study
The collected data may help discovering novel associations between genetics and phenotypic traits. These assosiations will, in turn, assist in identifying new targets for drug development or biomarkers. This study underscores the potential of SVs in enhancing the understanding of the genetic factors that influence complex diseases, and incorporating SVs in post-GWAS gene-prioritization approaches might therefore become standard practice.
It is our hope that making the panel available through opnMe will accelerate research on the genetic underpinnings of diverse diseases and facilitate the identification of novel therapeutic concepts.
About the Genomic lens study
The Genomic lens project is a collaboration between scientists from two Boehringer Ingelheim departments, the Global Computational Biology and Digital Sciences (gCBDS), and BI X, the Digital Lab of Boehringer Ingelheim.
1Noyvert B., Erzurumluoglu A. M., Drichel D., Omland S., Andlauer T. F. M., Mueller S., Sennels L., Becker C., Kantorovich A., Brænne I., Bartholdy B. A., Belbin G. M., Li J. H., Pickrell J. K., de Jong J., Arora J., Kriegl J., Podduturi N., Jensen J. N., Stutzki J., Ding Z. Imputation of structural variants using a multi-ancestry long-read sequencing panel enables identification of disease associations; eLife14:RP106115; https://doi.org/10.7554/eLife.106115.1
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About opnMe:
opnMe.com, the open innovation portal of Boehringer Ingelheim, fosters science and collaboration initiatives in areas of high unmet medical need. As part of our first pillar, the “Molecules to Order”, we share well-characterized tool compounds free of charge with no IP strings attached. These are complemented by “Molecules for Collaboration” where we offer access to unprecedented, often unpublished molecules, together with an attractive funding package. Interested scientists are invited to submit testable research hypotheses with these assets in novel diseases or combinations. With our “opn2EXPERTS” and “techMATCH” programs, we enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs. Our opn2TALENTS PostDoc grants provides an opportunity for high-caliber talents to pitch their scientific approaches for well-defined research questions to conduct their research at our discovery research site Biberach, Germany
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