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Issue link: https://clinicalomics.epubxp.com/i/827649
www.clinicalomics.com May/June 2017 Clinical OMICs 35 tions that likely act through altered splicing, the work also provides strong evidence that some exons are especially prone to splice-altering mutations," Dr. Rosenberg noted. To further validate MaPSy's results, the team also tracked down patient tissues samples from the original clin- ical studies that reported the genetic mutations. Though they were only able to track down samples linked to 32 of the MaPSy-detected exonic splicing mutations, they were able to validate 81% of those variants by con- ducting RNA splicing analyses on the tissues. "The type of massively parallel reporter assay used in this work is a powerful tool towards uncovering pathogenic variants that alter splic- ing," Dr. Rosenberg said. "I expect that this approach and similar ones will be scaled up to test even larger sets of potential splice-altering variants." A few years ago, Dr. Fairbrother and his colleagues created Spliceman , a freely available web-based tool for predicting how likely mutations in DNA sequences are to cause splicing errors. Currently, the team is looking for ways to improve MaPSy. One of their goals, Dr. Fairbrother noted, is to synthesize longer regions of DNA— presently, the system can only test mutation in exons that are less than 100 nucleotides long. They also hope to expand that assay to test more mutations at once. "In this study, we tested 5,000 mutations," he said. "Now, we're testing around 20 to 30 thou- sand variants." Genomic Signature Predicts Acute Rejection in Liver Transplant Patients Josh Levitsky, M.D., professor of medi- cine (gastroenterology, hepatology) and surgery (organ transplantation) at North- western University Feinberg School of Medicine, presented results from a sin- gle-center discovery and internal val- idation study that detailed a recently discovered genomic signature for pre- dicting acute rejection in liver transplant (LT ) recipients. "We have identified blood and graft mRNA signatures that can distinguish AR from other major causes of graft injury in LT recipients and may be useful in the monitoring and management of LT recipients," Dr. Levitsky and colleagues concluded in an abstract of their pre- sentation at the American Transplant Congress (ATC) in Chicago titled "Blood and Biopsy Genomic Signatures of Acute Rejection in Liver Transplant Recipients." The study examined gene expression profiles in the peripheral blood and biopsy tissue of liver transplant recip- ients. Of the 181 patients enrolled, 45 showed normal function; 45 elevation in liver function tests (LFTs), with a biopsy showing acute rejection (AR); and 91, abnormal LFTs with no clinical or histo- logical evidence of AR. Using Affymetrix gene -expression BluezAce / Getty Images (continued on next page) dem10/ Getty Images lvcandy / Getty Images