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A research team led by Cleveland Clinic has developed a personalized genomic medicine platform that will help accelerate genome medical research and genome-based drug discovery. This is evident from new study results recently published in Genome Biology.

Known as My Personal Mutanome (MPM), the platform has an interactive database that provides insight into the role of disease-associated mutations in cancer and prioritizes mutations that may respond to drug therapies.

“Although advances in sequencing technology have provided a wealth of cancer genomic data, the ability to bridge the translational gap between large-scale genomic studies and clinical decision-making has been lacking,” said Feixiong Cheng, Ph.D., assistant at the Cleveland Clinic Genomic Medicine Institute and lead author of the Study. “MPM is a powerful tool that helps identify novel functional mutations / genes, drug targets, and biomarkers for cancer, accelerating progress toward cancer precision medicine.”

Using clinical data, researchers have integrated nearly 500,000 mutations from over 10,800 tumor exomes (the protein-coding part of the genome) across 33 cancers to develop the comprehensive database of cancer mutations. They then systematically mapped the mutations to over 94,500 protein-protein interactions (PPIs) and over 311,000 functional protein sites (where proteins physically bind to one another), and recorded data on patient survival and drug response.

The platform analyzes the relationships between genetic mutations, proteins, PPIs, protein functional sites and drugs to make it easy for users to find clinically actionable mutations. The MPM database contains three interactive visualization tools that provide two- and three-dimensional views of disease-associated mutations and the associated survival and drug responses.

The results of another study published in Nature Genetics, a collaboration between the Cleveland Clinic and several other institutions, motivated the team to develop the platform.

Previous studies have linked the pathogenesis and progression of disease to mutations / variations that disrupt the human interactome, the complex network of proteins and PPIs that affect cell function. Mutations can disrupt the network by changing the normal function of a protein (nodetic effect) or by changing PPIs (edgetic effect).

Specifically, in the Nature Genetics study conducted by Brigham & Women’s Hospital and Harvard Medical School, researchers found that disease-associated mutations were highly accumulated where PPIs occurred. They also showed that PPI-altering mutations correlated significantly with drug sensitivity or resistance, as well as poor survival rates in cancer patients.

Overall, MPM enables a better understanding of mutations at the human interactive network level, which can lead to new insights in cancer genomics and treatment and ultimately help achieve the goal of personalized cancer care. The team will update MPM annually to provide researchers and clinicians with the most complete data available.

“Our study of natural genetics also shows the effects of mutations / variations in other diseases,” added Dr. Cheng added. “As a next step, we are developing new artificial intelligence algorithms to translate these genomic medical insights into drug target identification and precision drug discovery for other complex diseases, including heart disease and Alzheimer’s disease.”

The study shows that endometrial cancer patients in Kentucky have a higher rate of DACH1 mutations

More information:
Yadi Zhou et al., My Personal Mutanome: A Platform for Computational Genomic Medicine to Search for Network Disrupting Alleles Linking Genotype to Phenotype, Genome Biology (2021). DOI: 10.1186 / s13059-021-02269-3

Cheng, F., Zhao, J., Wang, Y. et al. Comprehensive characterization of protein-protein interactions that are disrupted by disease mutations. Nat Genet (2021). doi.org/10.1038/s41588-020-00774-y, www.nature.com/articles/s41588-020-00774-y

Provided by the Cleveland Clinic

Quote: Researchers are developing a platform to identify cancer mutations potentially responsive to drug therapies (2021, February 8), accessed February 8, 2021 from https://medicalxpress.com/news/2021-02-platform-cancer-mutations -responsive-drug. html

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