Proteomic-Based Biomarker Discovery with Emphasis on Cerebrospinal Fluid and Multiple Sclerosis

Abstract

Discovery of disease specific biomarkers in human body fluids has become an important challenge in clinical proteomics. Facing the increasing threat of degenerative and disabling diseases like cancer, cardiovascular, neurological and inflammatory diseases in large parts of the world's population, there is an urgent need to improve early diagnostics. In this review we discuss possibilities and limitations connected to using mass spectrometry based proteomics in the search for novel biomarkers, with focus on multiple sclerosis as a typical representative for the large group of non-curable degenerative and disabling disease with the lack of specific tests for early diagnosis. Careful control of the pre-analytical phase including sampling, storage and fractionation of samples, in addition to a thoroughly considered patient selection, is important in order to avoid false biomarkers to appear in the resulting mass spectra. Furthermore, advanced computational tools are needed in order to discover potential biomarkers from the enormous data amounts generated by the mass spectrometers. The development of such computer tools is a research field currently in the start phase and could prove to be a bottle neck in the biomarker discovery the next years. Therefore, a rather detailed review of the most used computational and pre-analytical methods is given in this review. Mass spectrometry based biomarker discovery is undoubtedly still in its early infancy. However, in light of the potential of this technology to provide deep coverage of the body fluid proteomes, it will certainly consolidate its role in developing molecular medicine into clinical practice.

Application of proteomics to ecology and population biology

“…The application of MS-based techniques for the qualitative and quantitative analysis of cellular proteomes, often from complex mixtures, has become an important tool for the understanding of cellular function across a wide diversity of plant and animal taxa (Fels et al, 2003;Han and Lee, 2003;Ahram and Springer, 2004;Aldred et al, 2004;Banta-Wright and Steiner, 2004;Chen and White, 2004;Baginsky and Gruissem, 2006;Berven et al, 2006;Bowler et al, 2006;Hitchen and Dell, 2006) Historically, MS has been a workhorse analytic tool used by chemists and associated industries, where it is mainly used as a tool for structural determination of organic compounds and quality control assurance in the pharmacetutical and biotech industries. MS is also a prominent tool used by security agencies, for example in rapid detection of explosive materials at airports (Takats et al, 2004(Takats et al, , 2005a Over the past two decades, a number of major advances in MS technologies applied to the analysis of proteins and peptides has elevated MS to a central role in proteomics, including new methods for the introduction of complex protein and peptide mixtures into the mass spectrometer in such a manner as to allow for the de novo sequencing of small peptides (Lin et al, 2003;Yates, 2004;Gingras et al, 2005;Guerrera and Kleiner, 2005;Domon and Aebersold, 2006) Combined with the ever-expanding availability of whole, or partial, genome sequences and bioinformatic tools for their analysis, MS has assumed a primary role in proteomic analyses.…”

Protéomique et hépatites auto-immunes : techniques et résultats

“…Pour ce faire, on compare le protéome des cellules du tissu malade ou exposé à une substance à celui du tissu sain. C'est ainsi que des biomarqueurs de maladies autoimmunes ont été identifiés dans le liquide céphalorachidien de patients atteints d'une maladie de Guillain-Barré [63,78] ou de sclérose en plaque [12,29], dans l'humeur aqueuse de la rétinopathie diabétique [35], dans la salive de malades atteints d'un syndrome de Gougerot-Sjögren [107], dans les urines de la néphropathie à IgA [102], dans le liquide synovial de patients atteints de polyarthrite rhumatoïde [2,81].…”

Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology

“…Thus, the search for new, highly sensitive and specific markers, and combinations or signatures of multiple markers, has been intensive. The circulatory proteome has become one of the most promising molecular archives for the discovery of biomarkers of human diseases (14)(15)(16)(17). Even as some investigators have turned their attention to urine and abdominal fluid as a source of molecular diagnostic information for prostate and ovarian cancers, among all physiological fluids, human plasma and serum have become the most intensively investigated biological samples.…”