Deciphering the mysteries of the human genome
Scientists from the Icahn School of Medicine at Mount Sinai (NY, USA) have unveiled LoGoFunc, a cutting-edge computational tool set to revolutionize genetic research. Published in Genome Medicine, this innovative model can predict pathogenic gain- and loss-of-function variants, promising to advance our comprehension of diverse disease outcomes and accelerate precision medicine.
Current traditional methods of identifying harmful mutations mainly concentrate on identifying loss of function variants, leaving a crucial gap in understanding the full spectrum of genetic mutations. Cue LoGoFunc, which, unlike its predecessors, can distinguish between loss of function and gain of function variants.
The tool works by employing machine learning, trained on a vast database of known pathogenic mutations. LoGoFunc accounts for 474 biological features, incorporating data from AlphaFold2-predicted protein structures and network features based on human protein interactions.
Validated on datasets from the Human Gene Mutation Database and ClinVar, the tool performed with impressively high accuracy when predicting loss-of-function, neutral, and gain-of-function variants.
Avner Schlessinger, Associate Director of the Mount Sinai Center for Therapeutics Discovery, stated, “beyond personalized medicine, LoGoFunc has implications for drug discovery, genetic counseling, and accelerating genetic research. Its accessibility promotes collaboration and offers a comprehensive view of variant impact across the human genome.” LoGoFunc’s accessibility opens new avenues for precision medicine, potentially enabling more tailored treatments based on individual genetic makeup.
Although these results represent considerable progress, the researchers caution that it is necessary to further validate and integrate the findings with additional medical information before translating them into clinical practice. Continuous validation efforts are essential for ensuring the reliability of LoGoFunc’s predictions.
With the continuous growth of genetic data, the team underscores the importance of prioritizing the enhancement and expansion of LoGoFunc’s capabilities in upcoming research endeavors. The tool provides openly accessible predictions for missense variants throughout the entire genome, catering to non-commercial use and analysis. This accessibility holds the potential to unravel the complexities of the human genome, marking a significant step toward the development of personalized treatment strategies.
