“In all stages of biomarker discovery, it is extremely important to know the identities of differentially expressed metabolic components as compared to viewing them solely as statistical objects,” states Robert Mistrik, Ph.D., and CEO at HighChem, who will discuss the challenges posed by structural profiling of endogenous metabolites.
Metabolic profiling, a widely used tool today, compares two groups of individuals —a sample of normal controls and a matched group of diseased individuals. Scanning the levels of many metabolites, profiles for individuals can be obtained and differences noted between the various groups. Consistent alterations in metabolite expression can reveal significant features of a disease process not obtainable through other approaches.
The company’s main thrust is the development of software solutions for crunching complex analytical data. The analysis is aimed at low molecular weight substances, that is, nonpeptide or proteinaceous materials. Other areas of interest include comprehensive libraries of fragmentation knowledge and experimental spectral data.
Much of the company’s efforts involve the development of an accurate mass search tool for analyzing structural libraries. The traditional approaches adopted by HighChem include spectra searches against reference libraries, multivariate pattern-recognition methods, biochemical pathway analysis, and direct spectra interpretation.
To facilitate this analysis, HighChem is pursuing an extension of its spectral library of endogenous metabolites referred to as spectral trees, according to Dr. Mistrik. Mass spectrometers are usually coupled to either liquid chromatography or gas chromatography devices, which yield data with divergent properties resulting from the different features of the two separation technologies.
HighChem software allows the spectral trees to be reconstructed from data files, extracting and comparing informative data from both LC and GC characterization. “It is possible to store and search trees in libraries, to annotate every node spectrum or to create chromatographic libraries with spectral tree components,” states Dr. Mistrik.
One of the important collaborative efforts that HighChem is involved in is the METAcancer project, a large consortium currently investigating breast cancer in the EU. The company is investigating new biomarkers for early detection of breast cancer as part of the project.