Metabolomics overview
The metabolome constitutes the collective collection of low molecular weight components (<1500Da) in a biological system that could be cells, tissue, fluid or whole organisms. Metabolomics refers to the global and non-targeted quantitative analysis of the metabolome. While transcriptomics and proteomics profiles the gene transcription and protein translation respectively, metabolomics examines the ultimate down stream effect of changes in transcription and translation. Therefore, metabolomics could potentially provide us with molecular events close to the phenotype(s) under investigation.
Metabolomics at KBC
Our ambition is to integrate quantitative metabolomics with proteomics and transcriptomics to enable well resolved functional information on the dynamics between certain phenotypes and the underlying molecular interactions. A great challenge lies in the development of methods for metabolite measurement that are sufficiently general while still sensitive enough to detect the low abundant species and subtle concentration changes involved in transition between various phenotypes.
Biomarkers and metabolomics
A Biomarker is a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or responses to a therapeutic intervention. In a clinical context, metabolite concentration levels that can distinguish a normal biological state from a pathogenic process can be called diagnostic biomarkers whereas changes in metabolite concentrations that can predict propagation of a pathogenic process or indicate how well a patient is responding to a certain treatment are called prognostic biomarkers. Metabolomics can be used to define physiological/pathogenic processes as well as molecular deviations from these states.
Finding new biomarkers for the clinic
Various small molecules are today routinely used as markers for physiological/pathological conditions in the clinic. A few examples include; glucose (diabetes), phenylalanine/tyrosine ratio (Phenylketonuria), thyrotropin (hyperthyroidism), acylcarnitine’s (Glutaric Acidemia), prolactin (adrenal disorders) and urea (renal function). We are working towards both diagnostic biomarkers for lung cancer but also biomarkers that can be used to evaluate progress of an individually chosen therapy (personalized medicine). To facilitate screening of larger patient groups, the sample that is analyzed should optimally be obtained through non-invasive means (e.g. blood, saliva or urine). However in these sample types we could expect that potential biomarkers are fairly diluted which could make them unsuitable for initial metabolomics screening. At KBC we therefore also screen other material relevant for a certain phenotype such as tissue samples or cell lines in addition to patient serum samples. After initial identification of possible biomarkers, we develop targeted approaches to validate their concentration in the intended sample type (typically plasma or serum).
