UCLA and University of Toronto researchers have developed a powerful new tool which will further our understanding of how changes within our DNA affect proteins and ultimately, how those changes contribute to various diseases or conditions. The tool provides a novel approach to diagnostic testing, opening the door to unexplored treatment targets which were previously not known to researchers.
The work, published in Nature Biotechnology, overcomes hurdles common in the field of proteogenomics, specifically the challenges faced when attempting to accurately detect variant peptides and identify genetic mutations at the protein level. The freely available tool, called moPepGen, allows researchers to precisely identify protein variations.
"We developed moPepGen to help researchers determine which genetic variants are truly expressed at the protein level, addressing a long-standing challenge in the proteogenomic community," said Chenghao Zhu, Ph.D., a postdoctoral scholar at the department of human genetics at UCLA.
"Our tool significantly improves the detection of hidden protein variations by using a graph-based approach to efficiently process all types of genetic changes. This provides a more comprehensive view of protein diversity and gives researchers a much more accurate picture of how mutations influence disease."
Perhaps one of the most exciting applications of the tool is in the field of immunotherapy. By precisely identifying cancer-specific variant peptides which can be used as neoantigen candidates, moPepGen could be key to developing novel personalized cancer vaccines and cell therapies.
"By making it easier to analyze complex protein variations, moPepGen has the potential to advance research in cancer, neurodegenerative diseases, and other fields where understanding protein diversity is critical," said Paul Boutros, Ph.D., professor of urology and human genetics at the David Geffen School of Medicine at UCLA. "It bridges the gap between genetic data and real-world protein expression, unlocking new possibilities in precision medicine and beyond."