In the field of oncology, the quest for effective cancer therapies relies heavily on the identification of viable therapeutic targets. At The Hyve, collaboration is at the forefront of our strategy. This led The Hyve to leverage the combined potential of two open-source tools, allowing us to explore the integration of cancer-type data from cBioPortal and genetic variants into the Open Targets platform. Open Targets, a collaborative initiative dedicated to creating a comprehensive knowledge base of human disease targets, and cBioPortal, a leading resource for exploring multidimensional cancer genomics data, are joining forces thanks to The Hyve’s recent efforts. This exciting integration promises to revolutionize target discovery and prioritization, particularly for the large collection of cancer types included in cBioPortal. Another benefit of our proposed approach is drug repurposing, where certain drugs could be used to treat other cancers or other diseases. This process brings the drugs to preclinical and clinical trials faster, enhancing the drug development process and thus reducing risk and costs.
Identifying the Gap
The traditional approach to drug discovery often focuses on understanding the biological function of a specific target protein associated with a disease. However, this approach may oversimplify the complexity of human diseases. This is where multi-omic data, encompassing a wider range of biological information, comes into play.
The Open Targets Platform integrates diverse data sources, including genetic, genomic, proteomic and chemical data, providing a comprehensive resource for target discovery. However, its real-world cancer genomics data is nowhere near as rich as that in cBioPortal which would add a crucial dimension to the multi-omic approach of target discovery and validation for a large number of cancer types. Integrating data like spot-mutations and copy-number alterations from cBioPortal with the wealth of information available on Open Targets could be the key for a more comprehensive understanding of disease biology, especially in the field of oncology.
Bridging the Gap
The growth of curated public data within cBioPortal presents an opportunity to unravel the intricate associations between genetic variants and cancer types. Incorporating cancer genomic data into Open Targets represents a significant enhancement, addressing the current underrepresentation of cancer genomic data within the platform. This addition not only enriches overall target discovery but also significantly boosts drug repurposing efforts in the field.
The Hyve therefore has aspired to develop an integration of Open Targets and cBioPortal aiming to seamlessly bridge this gap. Researchers will be able to leverage cBioPortal data directly within the Open Targets Platform, putting all this unlocked potential right at their fingertips. Specifically, The Hyve has developed a pipeline that (1) extracts the frequency of genomic alterations from cBioPortal, (2) transforms this data from a study-record-oriented dataset to a gene-disease-oriented one and (3) maps the cBioPortal identifiers (such as Oncotree code and HUGO symbols) to Open Targets-compliant identifiers (e.g. EFO and ENSEMBL IDs; Figure 1).
By adding evidence on how specific genetic alterations relate to specific cancer types from cBioPortal into Open Targets, researchers can more effectively assess target-disease associations relevant to therapeutic success.
For example, for round cell liposarcoma (MONDO_0020561) the addition of cBioPortal data significantly altered the overall target-disease association scores. This led to a new top target, namely the telomerase reverse transcriptase gene (TERT; ENSG00000164362) (Figure 2), which is well described in literature (Figure 3), and is used as a target for several therapies currently in Phase II & III trials (Figure 4).
Though of course not conclusive evidence that TERT is a druggable target for round cell liposarcoma, it does indicate that the addition of cBioPortal data led to an enrichment of the target rankings that holds promise.
Regardless of how researchers decide to use the integration of Open Targets' information on disease pathways with cBioPortal's detailed cancer genomics data, they are sure to gain a deeper understanding of the underlying mechanisms of various cancer types thanks to the integration.
Crossing the Bridge
In short, The Hyve’s integration of Open Targets’ breadth of information, with cBioPortal’s depth has the potential to improve target selection, identification, prioritization and much more. By integrating various data types into the existing multi-omics framework, our bridge puts these improvements at your fingertips. Our Open Targets and cBioPortal integration signifies an important step forward for drug discovery and repurposing. Reach out to us now to get more information on how The Hyve can help you to start paving the way for the development of more effective and targeted therapies for patients suffering from a wide range of cancers.
cBioPortal