Diagnostic Proteomics: Will this impact the clinic?

Abstract

Sascha Sauer Over the last decades we have witnessed enormous progress in the life sciences in terms of in-depth knowledge but less in the development of groundbreaking new concepts. Modern life sciences are dominated by application of the very successful reductionist research paradigm of experimental physics and chemistry [1]. However, experimental manipulation and simple mechanistic interpretation may turn out to be inadequate in biology when dealing with interconnected and inherently non-separable processes, leading to technical or even fundamental limitations due to biological uncertainty of the various states of interacting molecules [2]. Recently, systematic data driven approaches were introduced to generate in a largely unbiased fashion hypotheses, and in the ideal case to monitor the expression and regulation of all relevant molecular key players such as proteins. However, complexity may in particular arise from causality structures [3], which cannot be easily deduced from the “parts of the sum” of single molecules and mechanistic interaction of a few key players. It seems that network-based interaction of molecules results in the important redundancy, plasticity and flexibility of biological systems including homeostatic regulation of the proteome, which would otherwise be too vulnerable to environmental perturbation or stochastic events [4]. The advent of new methodologies in the life sciences including proteomics raised hope to provide efficient tools for diagnosis and for monitoring of complex disease (treatments) [5]. But the transition of proteomics-based research to clinical practice is in general still inefficient. Clinical proteomics as other fields of the life sciences dealing with complex issues may benefit from developing innovative approaches, i.e. to adequately grasp the etiology and causality of diseases to eventually develop fruitful approaches and tools for efficient diagnostics and medication of diseases. In this Focus Issue on “Diagnostic Proteomics”, a number of concepts, methodologies and promising results are presented to advance the field of clinical proteomics. In a viewpoint, Ulrich Stelzl (contribution in this issue, pp. 727–732) discusses the importance of molecular networks for interpreting various large data sets including genetic variation and proteomics data, to better understand fundamental biological organisation principles and to comprehensively analyse disease processes [6]. During the last years, biological mass spectrometry based methods have been introduced for various potential clinical applications. For example, mass spectrometry based imaging methods have become promising tools to analyze on the molecular level the pathology of tissue samples [7]. Jeremy Norris and Richard Caprioli (contribution in this issue, pp. 733–738) provide a concise update on these methods and discuss future applications. Furthermore, protein-based diagnostic markers can be identified in discovery-driven approaches using high-throughput mass spectrometers [8]. In this context, Bruno Domon and co-workers (contribution in this issue, pp. 739–747) discuss newest developments in the field of (targeted) mass spectrometry (also [9]) to validate potential protein-based biomarkers for final application in diagnostic test systems such as ELISA. Clearly, all these endeavours in clinical proteomics and related fields would be useless without making well-organised efforts in standardising clinical samples for biomarker development and validation using genomics, proteomics or other modern methodologies [10]. In a Standardisation & Guidelines paper Gil Omenn (contribution in this issue, pp. 748–755) describes current efforts to establish solid grounds in this crucial field. Furthermore, it is well known that many research and diagnostic methods heavily rely on the use of well-validated protein binding molecules such as antibodies [11]. In a review, Mike Taussig and co-workers (contribution in this issue, pp. 756–766) give a thorough overview to guide the readers through the world of protein binders, which are key components of many diagnostic technologies. Recently, facile, robust and standardized mass spectrometry based methods have been successfully implemented in hundreds of microbiology laboratories. In particular MALDI-TOF