A decade of proteomics accomplished! Central and Eastern European Proteomic Conference (CEEPC) celebrates its 10th Anniversary in Budapest,Hungary

The Central and Eastern European Proteomic Conference (CEEPC) proudly celebrated its 10th Anniversary with an exciting scientific program inclusive of proteome, proteomics and systems biology in Budapest, Hungary. Since 2007, CEEPC has represented ‘state-of the-art’ proteomics in and around Central and Eastern Europe and these series of conferences have become a well-recognized event in the proteomic calendar. Fresher challenges and global healthcare issues such as ageing and chronic diseases are driving clinical and scientific research towards regenerative, reparative and personalized medicine. To this end, proteomics may enable diverse intertwining research fields to reach their end goals. CEEPC will endeavor to facilitate these goals.     

Parasitic diseases: opportunities and challenges in the 21st century

The opportunities and challenges for the study and control of parasitic diseases in the 21st century are both exciting and daunting. Based on the contributions from this field over the last part of the 20th century, we should expect new biologic concepts will continue to come from this discipline to enrich the general area of biomedical research. The general nature of such a broad category of infections is difficult to distill, but they often depend on well-orchestrated, complex life cycles and they often involve chronic, relatively well-balanced host/parasite relationships. Such characteristics force biological systems to their limits, and this may be why studies of these diseases have made fundamental contributions to molecular biology, cell biology and immunology. However, if these findings are to continue apace, parasitologists must capitalize on the new findings being generated though genomics, bioinformatics, proteomics, and genetic manipulations of both host and parasite. Furthermore, they must do so based on sound biological insights and the use of hypothesis-driven studies of these complex systems. A major challenge over the next century will be to capitalize on these new findings and translate them into successful, sustainable strategies for control, elimination and eradication of the parasitic diseases that pose major public health threats to the physical and cognitive development and health of so many people worldwide.     

Data merging for integrated microarray and proteomic analysis.

The functioning of even a simple biological system is much more complicated than the sum of its genes, proteins and metabolites. A premise of systems biology is that molecular profiling will facilitate the discovery and characterization of important disease pathways. However, as multiple levels of effector pathway regulation appear to be the norm rather than the exception, a significant challenge presented by high-throughput genomics and proteomics technologies is the extraction of the biological implications of complex data. Thus, integration of heterogeneous types of data generated from diverse global technology platforms represents the first challenge in developing the necessary foundational databases needed for predictive modelling of cell and tissue responses. Given the apparent difficulty in defining the correspondence between gene expression and protein abundance measured in several systems to date, how do we make sense of these data and design the next experiment? In this review, we highlight current approaches and challenges associated with integration and analysis of heterogeneous data sets, focusing on global analysis obtained from high-throughput technologies.     

A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory

Systems biology and the digital revolution are together transforming healthcare to a proactive P4 medicine that is predictive, preventive, personalized and participatory. Systems biology - holistic, global and integrative in approach - has given rise to systems medicine, a systems approach to health and disease. Systems medicine promises to (1) provide deep insights into disease mechanisms, (2) make blood a diagnostic window for viewing health and disease for the individual, (3) stratify complex diseases into their distinct subtypes for a impedance match against proper drugs, (4) provide new approaches to drug target discovery and (5) generate metrics for assessing wellness. P4 medicine, the clinical face of systems medicine, has two major objectives: to quantify wellness and to demystify disease. Patients and consumers will be a major driver in the realization of P4 medicine through their participation in medically oriented social networks directed at improving their own healthcare. P4 medicine has striking implications for society - including the ability to turn around the ever-escalating costs of healthcare. The challenge in bringing P4 medicine to patients and consumers is twofold: first, inventing the strategies and technologies that will enable P4 medicine and second, dealing with the impact of P4 medicine on society - including key ethical, social, legal, regulatory, and economic issues. Managing the societal problems will pose the most significant challenges. Strategic partnerships of a variety of types will be necessary to bring P4 medicine to patients.     

Advances and challenges in understanding the role of the lipid raft proteome in human health

ABSTRACT

Introduction: Phase separation as a biophysical principle drives the formation of liquid-ordered ‘lipid raft’ membrane microdomains in cellular membranes, including organelles. Given the critical role of cellular membranes in both compartmentalization and signaling, clarifying the roles of membrane microdomains and their mutual regulation of/by membrane proteins is important in understanding the fundamentals of biology, and has implications for health.

Areas covered: This article will consider the evidence for lateral membrane phase separation in model membranes and organellar membranes, critically evaluate the current methods for lipid raft proteomics and discuss the biomedical implications of lipid rafts.

Expert commentary: Lipid raft homeostasis is perturbed in numerous chronic conditions; hence, understanding the precise roles and regulation of the lipid raft proteome is important for health and medicine. The current technical challenges in performing lipid raft proteomics can be overcome through well-controlled experimental design and careful interpretation. Together with technical developments in mass spectrometry and microscopy, our understanding of lipid raft biology and function will improve through recognition of the similarity between organelle and plasma membrane lipid rafts and considered integration of published lipid raft proteomics data.     

Diffusion of synthetic biology: a challenge to biosafety

One of the main aims of synthetic biology is to make biology easier to engineer. Major efforts in synthetic biology are made to develop a toolbox to design biological systems without having to go through a massive research and technology process. With this “de-skilling” agenda, synthetic biology might finally unleash the full potential of biotechnology and spark a wave of innovation, as more and more people have the necessary skills to engineer biology. But this ultimate domestication of biology could easily lead to unprecedented safety challenges that need to be addressed: more and more people outside the traditional biotechnology community will create self-replicating machines (life) for civil and defence applications, “biohackers” will engineer new life forms at their kitchen table; and illicit substances will be produced synthetically and much cheaper. Such a scenario is a messy and dangerous one, and we need to think about appropriate safety standards now.     

Bottom up proteomics data analysis strategies to explore protein modifications and genomic variants

The quest to understand biological systems requires further attention of the scientific community to the challenges faced in proteomics. In fact the complexity of the proteome reaches uncountable orders of magnitude. This means that significant technical and data‐analytic innovations will be needed for the full understanding of biology. Current state of art MS is probably our best choice for studying protein complexity and exploring new ways to use MS and MS derived data should be given higher priority. We present here a brief overview of visualization and statistical analysis strategies for quantitative peptide values on an individual protein basis. These analysis strategies can help pinpoint protein modifications, splice, and genomic variants of biological relevance. We demonstrate the application of these data analysis strategies using a bottom‐up proteomics dataset obtained in a drug profiling experiment. Furthermore, we have also observed that the presented methods are useful for studying peptide distributions from clinical samples from a large number of individuals. We expect that the presented data analysis strategy will be useful in the future to define functional protein variants in biological model systems and disease studies. Therefore robust software implementing these strategies is urgently needed.     

Proteomic tools for biomedicine

Proteomic tools measure gene expression, protein activity and interactions of biological events at the protein level. Proteins are the major catalysts of biological functions and contain several dimensions of information that collectively indicate the actual rather than the potential functional state as indicated by mRNA analysis. Measurements can be made in terms of protein quantity, location, and time-point. For the future we see a further integration of existing and new technologies for proteomics from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology. This will further advance our knowledge of how biological systems are built up and what mechanisms control these systems. However, the potential of proteomics to comprehensively answer all biological questions is limited as only protein activity is measured. A unification of genomics, proteomics, and other technologies is needed if we are to start to understand the complexity of biological function in the context of disease and health.     

Perspectives in spicing up proteomics with splicing

In the post-genomics era there has been an acceleration of understanding of cellular and organismal biology and this acceleration has moved the goalposts for proteomics. Higher eukaryotes use alternative promoters, alternative splicing, RNA editing and post-translational modification to produce multiple isoforms of proteins from single genes. Switching amongst these isoforms is a major mechanism for control of cellular function. At present fundamental limitations in sensitivity, in absolute quantitation of proteins and in the characterization of protein structure at functionally important levels strongly limit the applicability of proteomics to higher eukaryotes. Recent developments suggest that quantitative, top-down proteomics analyses of complete proteins at sub-attomole levels are necessary for physiologically relevant studies of higher eukaryotes. New proteomics technologies which will ensure the future of proteomics as an important technology in medicine and cellular biology of higher eukaryotes are becoming available.     

Role and challenges of proteomics in pharma and biotech: technical, scientific and commercial perspective

Contemporary proteomics, currently in its exponential growth phase, is a bewildering array of tools. Proteomic methods are the result of a convergence of rapidly improving mass spectrometry technologies, protein chemistry and separation sciences, genomics and bioinformatics. Strides in improving proteomics technologies to map and measure proteomes and subproteomes are being made. However, no single proteomic platform appears ideally suited to address all research needs or accomplish ambitious goals satisfactorily. However, proteomics is in a unique position to contribute to protein discovery and to public health in terms of better biomarkers, diagnostics and treatment of disease. While the potential is great, many challenges and issues remain to be solved. Fundamental issues, such as biological variability, pre-analytic factors and analytical reproducibility, remain to be resolved. Neither an all-genetic approach nor an all-proteomic approach will solve biological complexity. Proteomics will be the foundation for constructing and extracting useful knowledge to pharma and biotech depicted in the following path: data --> structured data --> information --> information architecture --> knowledge --> useful knowledge.     

A proteomic view of mycobacteria

Tuberculosis, the disease caused by Mycobacterium tuberculosis, remains a relevant public health issue. This is due mostly to the coepidemiology with HIV/AIDS, the appearance of multidrug-resistant strains globally, and failure of BCG (bacillus Calmette-Guerin) vaccination to confer complete protection. This bacterium was one of the first to have its genome sequenced, yet over a decade after the release of the genomic information, the characterization of its phylogenetic tree and of different strain variants inside this species revealed that much is still needed to be done for a full understanding of the M. tuberculosis genome and proteome. Current methods using LC-MS/MS and hybrid high-resolution mass spectrometers can identify 2400-2800 proteins of the 4000 predicted genes in M. tuberculosis. In this article, we review relevant details of this bacterium's pathology and immunology, describing articles where proteomics helped the community to tackle some of the organism biology, from understanding strain diversity, cellular structure composition, immunogenicity, and host-pathogen interactions. Finally, we will discuss the challenges yet to be fulfilled in order to better characterize M. tuberculosis by proteomics.     

Proteomics and phosphoproteomics for the mapping of cellular signalling networks

Proteomics is transitioning from inventory mapping to the mapping of functional cellular contexts. This has been enabled by progress in technologies as well as conceptual strategies. Here, we review recent advances in this area with focus on cellular signalling pathways. We discuss genetics-based methods such as yeast two hybrid methods as well as biochemistry-based methods such as two-dimensional gel electrophoresis, quantitative proteomics, interaction proteomics, and phosphoproteomics. A central tenet is that by its ability to capture dynamic changes in protein expression, localisation and modification modern proteomics has become a powerful tool to map signal transduction pathways and deliver the functional information that will promote insights in cell biology and systems biology.     

Nutrient Sensing by Histone Marks: Reading the Metabolic Histone Code Using Tracing,Omics, and Modeling

Several metabolites serve as substrates for histone modifications and communicate changes in the metabolic environment to the epigenome. Technologies such as metabolomics and proteomics have allowed us to reconstruct the interactions between metabolic pathways and histones. These technologies have shed light on how nutrient availability can have a dramatic effect on various histone modifications. This metabolism–epigenome cross talk plays a fundamental role in development, immune function, and diseases like cancer. Yet, major challenges remain in understanding the interactions between cellular metabolism and the epigenome. How the levels and fluxes of various metabolites impact epigenetic marks is still unclear. Discussed herein are recent applications and the potential of systems biology methods such as flux tracing and metabolic modeling to address these challenges and to uncover new metabolic–epigenetic interactions. These systems approaches can ultimately help elucidate how nutrients shape the epigenome of microbes and mammalian cells.     

Moss systems biology en route: phytohormones in Physcomitrella development

The moss Physcomitrella patens has become a powerful model system in modern plant biology. Highly standardized cell culture techniques, as well as the necessary tools for computational biology, functional genomics and proteomics have been established. Large EST collections are available and the complete moss genome will be released soon. A simple body plan and the small number of different cell types in Physcomitrella facilitate the study of developmental processes. In the filamentous juvenile moss tissue, developmental decisions rely on the differentiation of single cells. Developmental steps are controlled by distinct phytohormones and integration of environmental signals. Especially the phytohormones auxin, cytokinin, and abscisic acid have distinct effects on early moss development. In this article, we review current knowledge about phytohormone influences on early moss development in an attempt to fully unravel the complex regulatory signal transduction networks underlying the developmental decisions of single plant cells in a holistic systems biology approach.