Clinical OMICS

MAY-JUN 2017

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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Page 30 of 47 May/June 2017 Clinical OMICs 29 their bodies which interfere with the IHC test. "This is where mass spectrometry could be used for thy- roglobulin," said Dr. Kulasignam. "You'd find a proteotypic peptide, develop an SRM assay, and then just go after it because you won't have the interference of this other mol- ecule. That is what some groups have developed and are offering it routinely in the clinical diagnostic lab." In the Clinical Diagnostic Lab While wide adoption may still be low, mass spectrometry is poised to make a significant impact in the coming years in the clinical diagnostic lab. "There is currently a great oppor- tunity in that space because that is the end goal; to benefit patients using diagnostic assays that are not achievable by other means," said Dr. Castro-Perez. As Dr. Castro-Perez sees it, the development of targeted panels for diagnostics and the research into the discovery of validated biomarkers will go hand in hand and is part of the translational research continuum. "It will progress on both paths," he said, "and will require the development of instru- mentation that is fit for purpose for the biomarker discovery function, along with ready-to-use assays that have specific pathways, which clinicians will be interested in." But in the case of proteomics and metabolomics, the potential number of biomarkers to query makes this seems a daunting task. According to Dr. Castro-Perez, a key trend moving researchers away from a shotgun approach to tar- geted biomarker research are requests from clinicians. "More than ever there is interest from clinicians." he con- cluded. "In the past it was a first pass shotgun approach— let's see if we can find an interesting signature and go from there. That was the old days. But clinicians think very dif- ferently now. They are very issue and hypothesis driven." Dr. Cheema agrees, and thinks leveraging MS tech- nologies via a top-down approach to proteomic research will help drive translation of new findings into the clinic. "Listening to people from the clinic, and understanding what their challenges are and what they would like allows researchers to design approaches for questions that are yet unanswered in areas of need," she said. While focusing on one or two biomarkers to provide clin- ically relevant information is one pathway, Dr. Kulasingam thinks the future also holds potential for broader assays. "The future, I think, is in using proteomics and mass spec- trometry for global profiling in the clinical diagnostics lab. We already have one such assay that looks at the biopsy tis- sue of individuals that have a disease called amyloidosis. If you take the tissue, digest it, and do a full proteome anal- ysis you can subtype that disease and make a diagnosis," she noted. "There will be many more opportunities to have global proteome profiling, whether from biopsy tissues or other biological samples." toms. They found that the model had excellent predictive power for distinguishing between culture-positive typhoid patients and patients with other types of tropical disease. "A major challenge in typhoid diagnosis is diagnosing true typhoid patients who have a negative blood culture result," explains first author Elin Näsström, a graduate student at Umeå University, Sweden. "We wanted to see if the detected metabo- lomics could help further distinguish these groups." The team's predictive model pinpointed five out of nine blood test negative samples that were actually typhoid positive. And three out of five patients who were suspected of typhoid from their symptoms were also indicated to be typhoid positive by their metabolite signature. To validate the signature further, the group studied an addi- tional collection of blood samples from patients in Bangla- desh and Senegal. They then compared these profiles against the original data from Nepalese patients, published in the 2014 study by Näsström et al. From these combined analyses, they identified 24 metabolites that were consistently different between patients who had typhoid and those who had other diseases including malaria. "Our results demonstrated a metabolite panel that can dis- tinguish typhoid from other fever-inducing diseases, provid- ing a new approach for typhoid diagnostics," noted Dr. Baker. "The next challenges are to corroborate these metabolites in larger patient numbers and try and incorporate them into sim- ple diagnostic test formats. This approach could be potentially expanded into other tropical diseases, eventually allowing for more accurate diagnosis and more effective treatment, and hopefully reducing the use of unnecessary antimicrobials." n Senior author Stephen Baker, Ph.D., of the Oxford University Clinical Research Unit in Vietnam is part of a team exploring the efficacy of diferentiating typhoid (right) from other tropical diseases through the use of mass spectrometry. decade3d / Getty Images Background: katerynakon / Deposit Photos

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