Current Genomics - Volume 12, Issue 6, 2011

Systems biology has a long history as a theoretical framework in biology, positing that cellular systems possess emergent properties that can only be explained by the interactions among the components of an organism rather than by any individual component in itself. With the advent of the genomic era, data sets encompassing systems-wide measurements of gene complements, transcription, and protein expression are becoming available. Thoughtful integration of these data can lead to a systems-level understanding of the components and dynamics of cellular machineries and the development of practical methods for inferring and constructing network models of these interactions is well under way. As the creation of plausible network models of cellular systems becomes possible, comparison of systems in an evolutionary light promises to reveal the evolutionary forces that shape these systems. Systems are dynamic and selectable, that is, they respond to pressures brought to bear by changes in their environment. Therefore, the application of the methods of evolutionary biology within a systems biology framework can aid in identifying the concerted changes that drive the emergence of new phenotypes. A better understanding of systems evolution will greatly advance our knowledge about the complexity of gene regulation and help identify new therapeutic targets for effective treatment of various diseases. This special issue of Current Genomics is intended to provide a forum for researchers to share their experiences on all aspects of genome and systems evolution. This issue includes a review article discussing about the proteomics techniques that are capable of generating high quality data for systems biology research: Chen et al. reviewed recent advances in proteolysis, a key procedure prior to mass spectrometry and peptide mapping in proteomic studies of gene function. They showed that the proteolysis strategies can be accelerated by various electromagnetic waves, such as microwave-accelerated protein digestion, infrared-assisted proteolysis, ultraviolet-enhanced protein digestion, laser-assisted proteolysis, and future prospects. This issue also includes two review articles with a special emphasis on the systems biology of bacteria, ideal model organisms for evolutionary analyses of genome plasticity and adaptive phenotypes. Tang's review is focused on microbial metabolomics, which involves fast, high throughput characterization of the metabolite complements of a microorganism, and thus summarizes the global outcome of the interplay between the developmental processes and the environment. Selected topics illustrate the impact of metabolomics on the understanding of systems microbiology. Zhou et al. provide an overview of the recent advances in Streptomyces biology that have been driven by high throughput technologies. The omics based studies have revolutionized the understanding of system control and regulation dynamics of this group of bacterial of medicinal and industrial importance. Evolutionary systems biology approaches have also been applied to biomedical studies. Cai et al. provide a phylogenomic overview of the origin, distribution, diversity, and evolution of malarial proteases, a class of promising therapeutic targets for combating this devastating infectious disease that is responsible for over 1 million deaths yearly. Klemcke et al. introduce a novel physiogenomic approach to the study of hemorraghic shock, a major cause of death throughout the world. Their findings in heritable quantitative trait loci, as well as potential epigenetic mechanisms that might influence survival time after severe hemorrhage, may lead to the improvement in survival of traumatic hemorrhage and provide knowledge of genetically-informed personalized treatments. Overall, these reviews provide a fascinating survey of the combination of systems thinking and evolutionary analysis across the biological spectrum. As modeling approaches improve and as more data from more species become available, the study of systems evolution will clarify the links among the genotype, the phenotype and the selective pressures arising from the organism's place in the environment. As an emerging field in the post genomic era, evolutionary systems biology promises to make profound contributions to our understanding of life.

Proteomics will contribute greatly to the understanding of gene functions in the post-genomic era. In proteome research, protein digestion is a key procedure prior to mass spectrometry identification. During the past decade, a variety of electromagnetic waves have been employed to accelerate proteolysis. This review focuses on the recent advances and the key strategies of these novel proteolysis approaches for digesting and identifying proteins. The subjects covered include microwave-accelerated protein digestion, infrared-assisted proteolysis, ultraviolet-enhanced protein digestion, laser-assisted proteolysis, and future prospects. It is expected that these novel proteolysis strategies accelerated by various electromagnetic waves will become powerful tools in proteome research and will find wide applications in high throughput protein digestion and identification.

Microbial metabolomics constitutes an integrated component of systems biology. By studying the complete set of metabolites within a microorganism and monitoring the global outcome of interactions between its development processes and the environment, metabolomics can potentially provide a more accurate snap shot of the actual physiological state of the cell. Recent advancement of technologies and post-genomic developments enable the study and analysis of metabolome. This unique contribution resulted in many scientific disciplines incorporating metabolomics as one of their “omics” platforms. This review focuses on metabolomics in microorganisms and utilizes selected topics to illustrate its impact on the understanding of systems microbiology.

Streptomyces is a group of soil bacteria of medicinal, economic, ecological, and industrial importance. It is renowned for its complex biology in gene regulation, antibiotic production, morphological differentiation, and stress response. In this review, we provide an overview of the recent advances in Streptomyces biology inspired by -omics based high throughput technologies. In this post-genomic era, vast amounts of data have been integrated to provide significant new insights into the fundamental mechanisms of system control and regulation dynamics of Streptomyces.

Malaria continues to be one of the most devastating global health problems due to the high morbidity and mortality it causes in endemic regions. The search for new antimalarial targets is of high priority because of the increasing prevalence of drug resistance in malaria parasites. Malarial proteases constitute a class of promising therapeutic targets as they play important roles in the parasite life cycle and it is possible to design and screen for specific protease inhibitors. In this mini-review, we provide a phylogenomic overview of malarial proteases. An evolutionary perspective on the origin and divergence of these proteases will provide insights into the adaptive mechanisms of parasite growth, development, infection, and pathogenesis.

Severe hemorrhage due to trauma is a major cause of death throughout the world. It has often been observed that some victims are able to withstand hemorrhage better than others. For decades investigators have attempted to identify physiological mechanisms that distinguish survivors from nonsurvivors for the purpose of providing more informed therapies. As an alternative approach to address this issue, we have initiated a research program to identify genes and genetic mechanisms that contribute to this phenotype of survival time after controlled hemorrhage. From physiogenomic studies using inbred rat strains, we have demonstrated that this phenotype is a heritable quantitative trait, and is therefore a complex trait regulated by multiple genes. Our work continues to identify quantitative trait loci as well as potential epigenetic mechanisms that might influence survival time after severe hemorrhage. Our ultimate goal is to improve survival to traumatic hemorrhage and attendant shock via regulation of genetic mechanisms and to provide knowledge that will lead to genetically-informed personalized treatments.

We present recent advances in the genetics of recurrent vertigo, including familial episodic ataxias, migraneous vertigo, bilateral vestibular hypofunction and Meniere's disease. Although several vestibular disorders are more common within families, the genetics of vestibulopathies is largely not known. Genetic loci and clinical features of familial episodic ataxias have been defined in linkage disequilibrium studies with mutations in neuronal genes KCNA1 and CACNA1A. Migrainous vertigo is a clinical disorder with a high comorbidity within families much more common in females with overlapping features with episodic ataxia and migraine. Bilateral vestibular hypofunction is a heterogeneous clinical group defined by episodes of vertigo leading to progressive loss of vestibular function which also can include migraine. Meniere's disease is a clinical syndrome characterized by spontaneous episodes of recurrent vertigo, sensorineural hearing loss, tinnitus and aural fullness and familial Meniere's disease in around 10-20%of cases. An international collaborative effort to define the clinical phenotype and recruiting patients with migrainous vertigo and Meniere's disease is ongoing for genome-wide association studies.