Mount Sinai Researchers Use “Blacklist” Computing Concept as Novel Method to Streamline Genetic Analysis
Screening method shows promise as a key to faster therapeutic innovation
Researchers at the Icahn School of Medicine at Mount Sinai and The Rockefeller University have discovered a new use for a long-standing computational concept known as “blacklisting,” which is commonly employed as a form of access or spam control, blocking unwanted files and messages. Using blacklisting as a filter to single out genetic variations in patient genomes and exomes that do not cause illness, researchers have successfully streamlined the identification of genetic drivers of disease. This method is described in the December 2018 issue of Proceedings of the National Academy of Science of the United States of America.
In whole-exome sequencing—the process of identifying variations in protein-coding genes to determine the genetic underpinnings of any given illness—tens of thousands of genetic variants are identified, but only a few are deemed pathogenic, meaning disease-causing. Traditionally, in order to identify pathogenic mutations, scientists must sift through considerable amounts of data and remove genetic variants that are unlikely to cause disease, slowing down the process of genetic analysis and, subsequently, clinical treatment. To address this cumbersome process, researchers from the Icahn School of Medicine and The Rockefeller University investigated and subsequently identified a large portion of the non-pathogenic genetic variants, from which the “blacklist” was generated. Following this, they developed a program, known as ReFiNE, and a corresponding webserver that other researchers can use to automate the creation of their own blacklists.
“Until now, there has been no viable published method for filtering out non-pathogenic variants that are common in human genomes and absent from current genomic databases,” said Yuval Itan, PhD, Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine and senior author of the publication. “Using the blacklist, researchers will now be able to remove genetic ‘noise’ and focus on true disease-causing mutations.”
Noting the data-centric society we live in, Dr. Yuval says efficiency is key. His hope is that this contemporary tool can be used by clinicians, researchers, and scientists across the globe to conduct genetic analysis more quickly and accurately, helping to accelerate the pace of genomic medicine.
This work was partially supported by NIH grants: P01AI061093, U24AI086037, R18AI048693, T32GM007280, R01AI088364, R01AI095983, R01AI127564, and the Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai.
Proceedings of the National Academy of Sciences Dec 2018, 201808403; DOI:10.1073/pnas.1808403116
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.