A team of researchers led by the Cleveland Clinic has developed a personalized genomic therapy platform that will help accelerate genomic medicine research and drug discovery with genome-informed drugs, according to new study results recently published in an Genome Biology.
Known as My Personal Mutanome (MPM), the platform features an interactive database that provides insight into the role of disease-related mutations in cancer and prioritizes potential mutations. responding to drug treatments.
While advances in sequencing technology have provided a wealth of cancer genomic data, the capabilities to bridge the translation gap between large-scale genomic studies and clinical conclusions were lacking. MPM is a powerful tool that helps identify new function mutations / genes, drug targets and biomarkers for cancer, thus accelerating progress toward precision cancer treatment. “
Feixiong Cheng, PhD, S.tudy L.ead A.uthor and Support Staff, Genomic Medicine Institute, Cleveland Clinic
Using clinical data, the researchers identified nearly 500,000 mutations from more than 10,800 tumor exomes (the protein-coding part of the genome) across 33 cancer types to develop the complete cancer mutation database.
They then routinely mapped the mutations to more than 94,500 protein-protein interactions (PPIs) and more than 311,000 active protein sites (where proteins bind physically to each other) and produce include patient survival and drug response data.
The platform analyzes the relationships between genetic mutations, proteins, PPIs, protein and drug action sites to help users find clinically viable mutations. The MPM database contains three interactive visualization tools that provide two- and three-dimensional views of disease-related mutations and the associated survival and drug responses.
The results of another study published in The genetics of nature, a collaboration between the Cleveland Clinic and several other centers inspired the team to develop the platform.
Previous studies have linked disease pathogenesis and progression to mutations / changes that disrupt human interactions, the complex network of proteins and PPIs that affect cell function. Variables can disrupt the network by altering normal protein function (nodetic effect) or by altering PPIs (ritual effect).
In particular, in the The genetics of nature a study, led by Brigham & Women’s Hospital and Harvard Medical School, found that disease-related mutations were significantly enhanced where PPIs occurred. They also showed that PPI mutation mutations were significantly associated with drug sensitivity or resistance as well as low survival rate in cancer patients.
Together, MPM enables a better understanding of mutations at the level of a human interactive network, which could lead to new perspectives in cancer genomics and treatment and ultimately help achieve the goal of care for cancer. The team updates MPM annually to provide researchers and physicians with the most complete data available.
“Our The genetics of nature studies also show the impact of mutations / changes in other diseases, “Dr. Cheng said.” As a next step, we are developing new artificial intelligence algorithms to translate these genomic treatment decisions into target identification. known drugs with human genome and precision treatment drug. search for other complex diseases, including heart disease and Alzheimer’s disease. “
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Magazine Reference:
Zhou, Y., et al. (2021) My personal mutanome: a computational genomic therapy platform for network discovery affecting alleles that connect genotype to phenotype. Genome Biology. doi.