Clinical OMICS

NOV-DEC 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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28 Clinical OMICs November/December 2018 there are downsides for users, such as the lack of user input and being based in the cloud. "The downside of the platform is that, in particular with the METLIN database, you can't down- load it," said Corey Broeckling, Ph.D., director of the Proteomics and Metab- olomics Facility at Colorado State Uni- versity. "Its value of being online is wonderful, but if you have the ability to do other things with the data, you can't actually utilize their database, like some of the other database tools." Beyond data repositories and data- bases, computational tools have also emerged that take a user 's spectral data and predict the compound's structure. Sumner 's group builds some of these computational tools, and while they can be helpful, he said that "typically there [are] still 50 to 90% of the compounds in our profiles that are unknown after searching those data- bases. Metabolite identification is the number one grand challenge that we face in metabolomics." Turning to the Crowds As the metabolomics field strives to identify compounds accurately and quickly, the incompleteness and imposed limitations of the more tra- ditional databases have led some researchers to take matters into their own hands. Groups have formed data- bases, along with analytical platforms, through crowdsourcing the metabolo- mics community. One platform in par- ticular is the Global Natural Products Social Molecular Networking (GNPS), which is made up of a database, data repository, and analysis tools. "The key reason for creating that infrastructure is so that we can capture knowledge and share knowledge with the community," said co-developer of GNPS Pieter Dorrestein, Ph.D., director (continued from previous page) Prospect of the Clinic Despite the trove of challenges in the metabolomics field, knowledge gained from metabolomic studies are beginning to translate to the clinic. It is an exciting prospect, given that compared to the oth- er omics, metabolomics is considered to be most closely tied to phenotype. "With metabolomics, it's really the only [omic] where you can effectively take the molecules that you're analyzing and put them back into the system and demon- strate that you can use these molecules to modulate the phenotype," said Gary Si- uzdak, Ph.D., senior director of the Scripps Center for Metabolomics. In contrast, he said, the primary utility of genomics and proteomics has traditionally been in the identification of biomarkers and elucida- tion of mechanistic information. A flurry of studies over the past year have shown how introducing a metabolite back into the system, whether in vitro or in vivo models, modulates phenotype. Exam- ples include, preclinical studies showing how taurine mediates multiple sclerosis response to therapy, or how succinate pro- tects against diet-induced obesity. One of the most notable studies was a Phase III clinical trial that showed oral supplemen- tation of L-glutamine alleviated pain re- sponse caused by disease among children and adults who had sickle cell anemia. Beyond the newest research, clinicians are starting to recognize the importance of metabolomics in human health. For example, some doctors might recom- mend coenzyme Q10 (CoQ10) supple- mentation for certain patients who are taking statins to lower cholester- ol levels. Because one of the side effects of statins is inhibition of CoQ10 production—which mani- fests as muscle soreness—CoQ10 supplementation can help coun- teract the muscle soreness. "Many clinical situations are now being investigated ,and investigated thoroughly," said Stephen Barnes, Ph.D., director of the Targeted Metabolomics and Proteomics Laboratory at the Univer- sity of Alabama at Birmingham. While the prospect of identifying all human metab- olites is a daunting task, "in the end, for clinical medicine, we may not need to know every metabolite," Barnes noted. —Christina Bennett n "In the end, for clinical medicine, we may not need to know every metabolite." —Stephen Barnes, Ph.D., University of Alabama at Birmingham Stephen Barnes, Ph.D., University of Alabama at Birmingham

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