A novel network-based approach for discovering dynamic metabolic biomarkers in cardiovascular disease

• Published in: PloS one 2018-12, Vol.13 (12), p.e0208953-e0208953
• Main Authors: Baumgartner, Christian, Spath-Blass, Verena, Niederkofler, Verena, Bergmoser, Katharina, Langthaler, Sonja, Lassnig, Alexander, Rienmüller, Theresa, Baumgartner, Daniela, Asnani, Aarti, Gerszten, Robert E
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Bioindicators; Bioinformatics; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Biomedical research; Cardiomyopathy; Cardiovascular diseases; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - physiopathology; Carnosine; Clinical medicine; Complexity; Computation; Computational Biology; Computer and Information Sciences; Computer applications; Computer networks; Data mining; Engineering; Graph representations; Graphical representations; Heart attack; Heart attacks; Humans; Information retrieval; Kinases; Kinetics; Mass Spectrometry; Medical equipment; Medicine and Health Sciences; Metabolic Networks and Pathways; Metabolism; Metabolites; Molecular dynamics; Molecular interactions; Myocardial Infarction; Novels; Pharmacology; Program verification (computers); Proteins; Proteomics; R&D; Research & development; Signatures; Time series
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0208953

Metabolic biomarkers may play an important role in the diagnosis, prognostication and assessment of response to pharmacological therapy in complex diseases. The process of discovering new metabolic biomarkers is a non-trivial task which involves a number of bioanalytical processing steps coupled with a computational approach for the search, prioritization and verification of new biomarker candidates. Kinetic analysis provides an additional dimension of complexity in time-series data, allowing for a more precise interpretation of biomarker dynamics in terms of molecular interaction and pathway modulation. A novel network-based computational strategy for the discovery of putative dynamic biomarker candidates is presented, enabling the identification and verification of unexpected metabolic signatures in complex diseases such as myocardial infarction. The novelty of the proposed method lies in combining metabolic time-series data into a superimposed graph representation, highlighting the strength of the underlying kinetic interaction of preselected analytes. Using this approach, we were able to confirm known metabolic signatures and also identify new candidates such as carnosine and glycocholic acid, and pathways that have been previously associated with cardiovascular or related diseases. This computational strategy may serve as a complementary tool for the discovery of dynamic metabolic or proteomic biomarkers in the field of clinical medicine.