Norwegian version

Public defence: Hanne Bendiksen Skogvold

Hanne Bendiksen Skogvold will defend her thesis “Global Metabolomics as a Tool in Clinical Research and Diagnostics” for the PhD programme in Engineering Science.

The trial lecture and public defence will also be streamed live.

Ordinary opponents:

Leader of the public defence: Associate Professor Astrid Oust Janbu, OsloMet


  • Abstract


    The human metabolism is a highly complex and dynamic system with thousands of chemical reactions taking place simultaneously to break down and synthesize molecules to produce energy and maintain life. The metabolome is the complete set of all metabolites, i.e., small molecules participating in the metabolism, in a sample or organism. Global metabolomics involves the comprehensive study of the metabolome. As metabolites are associated with a wide range of diseases and medical conditions, the use of global metabolomics in clinical research and diagnostics has a large potential for discovering biomarkers suitable for diagnostics and assessing treatment effects. However, a full-scale implementation of global metabolomics in diagnostics has not yet been realized.

    This doctoral study involved characterization and evaluation of liquid chromatography-mass spectrometry (LC-MS) based global metabolomics as a tool in clinical research and diagnostics. A key focus was given to analytical method development, the importance of preanalytical factors, and mapping of the biochemical consequences of both normal biological processes and medical conditions for clinical samples within Oslo University Hospital.

    Main findings

    A global metabolomics method with reversed phase LC and a Q Exactive Orbitrap MS was optimized and evaluated. The method was demonstrated to cover a large range of metabolites regarding polarity and other properties. The method detected expected metabolic changes induced by fasting. The ability to reveal expected changes induced by normal biological processes showed that the method is suitable for global metabolomics studies with DBS of human samples in a clinical setting.

    The developed method was used to assess the effects of preanalytical factors on the dried blood spot metabolome. Dried blood spots of cases of sudden infant death syndrome and controls, collected during autopsy, were used. We compared two groups of samples that differed in storage time, storage temperature and type of filter card. We observed both accumulations and degradations of metabolites as a consequence of preanalytical differences. The findings demonstrated that the method was able to reveal metabolite alterations caused by preanalytical differences, and that the dried blood spot metabolome is heavily affected by preanalytical factors. Our findings emphasize the importance of ensuring identical preanalytical factors for the groups to be compared in global metabolomics.

    The cause of an intoxication of a young boy was uncovered with the use of the developed method, showing the method’s ability to discover biomarkers. The patient was revealed to suffer from acute and severe 3-nitropropionic acid intoxication. The finding of the toxin was highly unexpected, as the forensic toxicology screening of the patient samples did not detect any toxicants. By comparing samples taken at various stages of the intoxication, including the healthy follow-up phase, we performed a wide metabolic mapping showing alterations especially in the glycolysis and citric acid cycle, in line with the widespread metabolic disturbances caused by 3-nitropropionic acid blocking a central enzyme in both the citric acid cycle and the electron transport chain.


    Our developed global metabolomics LC-MS method proved to be suitable for wide metabolome coverage, detection of metabolic alterations caused by normal biological processes, preanalytical factors and an acute medical condition, and detection of biomarkers. This thesis demonstrates the suitability of global metabolomics using LC-MS for clinical research and diagnostics in a university hospital setting like Oslo University Hospital.


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