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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28 Clinical OMICs May/June 2017 gene deletion or certain mutations in a specific biochemical pathway. This can also be utilized as a vehicle to identify target genes that can we use for target validation in humans since we can now build genetic association with causal- ity for the disease. This biomarker association analysis obtained using mass spectrometry may also help to develop therapeutic drugs that can improve the lifestyle and health of an individual. This is where I see the implementation of this technology can really take a huge leap forward, because the economics behind it makes a lot of sense." The potential for mass spectrometry to play a prognostic role in care is also continuing to evolve. Amrita Cheema, Ph.D., who is a professor in the department of oncology at Georgetown University School of Medicine, is using mass spectrometry to identify biomarkers that are indicative of the accidental or intentional exposure to radiation, and also biomarkers for the early detection of pancreatic cancer. Currently, the lab where Dr. Cheema works has National Cancer Institute funding to discover biomarkers predictive of patient outcomes who undergo radiation therapy. "The idea is to develop a diagnostic kit that will be available in a high-throughput format, to run in a clinical mass spec lab," she said. "So the doctors can have the information on whether the patient will benefit from the therapy or not." While mass spectrometry-based tests for proteins and metabolites are slowly making their way into the clinical diagnostic arsenal, it some cases it is unlikely they will com- pletely supplant some established testing methods, such as immunohistochemistry. However, there may be a role for MS-based tests in cases where IHC can't accurately diag- nose all patients. One such area where mass spec plays a role is in monitor- ing thyroid cancer patients for the presence of thyroglobu- lin. Typcially, doctors will order an IHC thyroglobulin test for patients who have been treated for thyroid cancer to make sure the treatment was successful. No thyroglobulin present indicates the patient is cancer free. Unfortunately, IHC accurately measures thyroglobulin in only 90% of patients. The other 10% percent of the popu- lation have anti-thyroglobulin autoantibodies circulating in (continued from previous page) An international team of researchers recently published a new study which identified a metabolite signature that can accu- rately distinguish typhoid from other tropical diseases using patient blood samples and analyzed using mass spectrometry. The research study "Reproducible Diagnostic Metabolites in Plasma from Typhoid Fever Patients in Asia and Africa", pub- lished in eLife, builds on previous results from 2014 showing that metabolite markers can distinguish between typhoid infec- tion caused by different organisms. Many tropical diseases, such as typhoid and malaria, present with similar symptoms, making accurate diagnosis challenging and delaying effective treatment. A further problem with diag- nosing typhoid is that currently available tests are not sensitive enough, and some patients are later found to have the disease, even though an organism cannot be cultured from their blood. The investigators relied on metabolomics to try and identify metabolite patterns that are unique to different diseases. In a previous study, they used this method to identify metabolic sig- natures that could differentiate between typhoid caused by two closely related organisms—Salmonella Typhi and Salmonella Paratyphi A. "We wanted to assess if metabolomics could accurately diag- nose typhoid in patients from different regions with a wider range of tropical diseases," says senior author Stephen Baker, Ph.D., molecular microbiologist at Oxford University Clinical Research Unit, Vietnam. "We thought that this approach would more closely reflect the real situation where patients with fever-inducing diseases present with nonspecific symptoms." Dr. Baker and his research collaborators collected blood sam- ples from multiple patients from Bangladesh that fell into three groups: patients who had S.Typhi in their blood, those who were suspected of having typhoid from their symptoms, and a third group who were suspected of having a different tropical disease characterized by fever (a fever-control group). Using mass spectrometry, the team analyzed the metab- olites in each patient's blood sample to generate a metabolic signature for two patient groups: those whose blood tested positive for typhoid, and fever controls. They then used this as a model to predict the identity of individual samples in a third group: patients suspected of having typhoid from their symp- Mass Spec IDs Metabolite Signature for Typhoid Fever Today's mass spec tools require less specialized training. Waters Corperation

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