Bioinformatics platform for biomarker identification for End Stage Renal Disease through GC/MS metabolomics
Zusammenfassung der Projektergebnisse
In summary, the following aims have been reached during my appointment at MIT. 1. Implementation and evaluation of a high-throughput analysis pipeline for analyzing GC/MS based metabolomics data including the determination of statistically relevant biomarkers. Most parts of the pipeline have been included in the MetaboliteSoftware package. The software is freely available at http://metabolitedetector.tu-bs.de. 2. In deviation to the proposed project, I used human lung tumor samples for metabolic biomarker determination. Therefore, the developed analysis pipeline was applied to a GC/MS dataset recorded for metabolite extracts of tumor and healthy lung tissue samples obtained by biopsy from 14 lung cancer patients. The samples were provided by Prof. Tim Lautenschläger from the Radiology Department of the Ohio State University. The analysis revealed more than 20 tumor specific biomarkers. 3. In addition to the proposed project, the Non-targeted Tracer Fate Detection (NTFD) system was developed. NTFD is a combination of an experimental and algorithmic framework to detect all labeled compounds present in a GC/MS chromatogram derived from a stable-isotope labeled tracer. In addition, NTFD provides mass isotopomer distributions (MIDs) for all detected compounds. These MIDs are linked to the activities of participating enzymes. Thus, NTFD provides a non-targeted fingerprint of enzyme activities. To facilitate the application of NTFD, the algorithms have been implemented in a C++ and Qt4 based software freely available at http://ntfd.mit.edu. 4. The NTFD methodology was applied to elucidate the metabolic fate of glucose in human lung cancer cells (A549 cell line). Surprisingly, NTFD revealed metabolites derived from uniformly 13 C labeled glucose, which are not known to participate in human metabolism. Further research to unravel the underlying pathway is under progress.
Projektbezogene Publikationen (Auswahl)
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2009. Non-Targeted Metabolomics: From Biomarker Discovery to the Metabolic Fate of Compounds, Institute for Systems Biology, Seattle, USA
Karsten Hiller
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2010. Non-targeted elucidation of metabolic pathways using stable-isotope tracers and mass spectrometry. Analytical Chemistry, 82(15), pp.6621-6628
Hiller, K. et al.
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2010. Stable-isotope assisted and non-targeted analysis of cellular metabolism: Generating global fingerprints of enzyme activity. German Conference on Bioinformatics 2010, Braunschweig, Germany
Hiller, K. et al.
