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Bioinformatics meets systems biology
Carlos Salazar, Jana Schütze, Oliver Ebenh?h
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-1-303
Abstract: The efficient integration of bioinformatics and systems biology requires worldwide cooperation not only in the research of senior scientists but also in the research training of young scientists. To this end, a student-focused workshop on bioinformatics and systems biology http://www.biologie.hu-berlin.de/gk/ibsb2005 webcite was held last August at Humboldt University in Berlin, Germany. This was the fifth annual workshop held as part of a research collaboration between the Bioinformatics Program of Boston University in the USA, the Bioinformatics Center of Kyoto University in Japan, and the Berlin-located graduate program 'Dynamics and Evolution of Cellular and Macromolecular Processes'. This time the meeting had two main themes - the integration of genomic and chemical information in the analysis of the dynamics and topology of cellular regulatory networks, and the development of more accurate computational tools for the analysis of gene expression and the prediction of transcription-factor binding sites. Full papers accepted for the fifth workshop have been published in the Genome Informatics Series of the Japanese Society of Bioinformatics, edited by Satoru Miyano (University of Tokyo, Japan) http://www.jsbi.org/journal/GI16_1.html webcite.Trends in genome biology and bioinformatics were highlighted in the opening talk by Minoru Kanehisa (Kyoto University Bioinformatics Center, Japan), whose group is responsible for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database http://www.genome.ad.jp/kegg webcite. This stores molecular interaction networks and graphics, including metabolic pathways, regulatory pathways and molecular complexes. Kanehisa emphasized the importance of an integrated analysis of genomic and chemical information to predict the complete functional behaviors of cells, organisms and ecosystems. While traditional genomics and other 'omics' have contributed to our knowledge of the genes and proteins that make up a biological system, new chemi
Meeting report: Signal transduction meets systems biology
Christine Louis-Dit-Sully, Katharina F Kubatzky, Jonathan A Lindquist, Christine Blattner, Ottmar Janssen, Wolfgang W A Schamel
Cell Communication and Signaling , 2012, DOI: 10.1186/1478-811x-10-11
Abstract: As cellular constituents of the adaptive immune system, T cells carry an individual T cell antigen receptor (TCR)/CD3 complex with which they recognize specific antigens, resulting in activation of the cell and the mounting of an immune response [1,2]. However, to initiate a successful immune response against pathogens, without creating an inappropriate response against self-antigens, T cells have to discriminate between healthy cells of the body and diseased or infected cells. It is thought that the affinity of antigens to the TCR/CD3 complex governs this discrimination during intrathymic development. In the periphery, infected and diseased cells will present specific ‘foreign’ antigens with high affinity to the TCR leading to activation of the T cell. Due to the selection process, peripheral self-antigens have low or no binding-affinity and should not result in T-cell activation, but might rather be involved in T-cell survival. If the multiple backup systems of central and peripheral tolerance fail, T cells with high affinity to self-antigens might cause autoimmunity.T-cell activation is a complex process relying on multiple layers of tightly controlled intracellular signalling modules that form an intricate network. In order to gain systems-level insight into critical modules of the network and finally into the behaviour of the complete network, the SYBILLA consortium was founded. It groups 18 partners from 9 different EU countries, including a management company (Novamen, Lyon, France; represented by Sandrine Rival in SYBILLA), and coordinated by Wolfgang Schamel (Freiburg, Germany). Detailed information can be found at http://www.sybilla-t-cell.de webcite.The current development of several ongoing projects has been reported at the meeting and will be described below. In essence, through a multidisciplinary effort, SYBILLA aims to understand at the systems level, how T-cells discriminate foreign from auto-antigens, how T cells differentiate from naive cells into
Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna
Lars-Henrik Heckmann, Richard M Sibly, Richard Connon, Helen L Hooper, Thomas H Hutchinson, Steve J Maund, Christopher J Hill, Anthony Bouetard, Amanda Callaghan
Genome Biology , 2008, DOI: 10.1186/gb-2008-9-2-r40
Abstract: Our findings reveal intriguing similarities in the mode of action of ibuprofen between vertebrates and invertebrates, and they suggest that ibuprofen has a targeted impact on reproduction at the molecular, organismal, and population level in daphnids. Microarray expression and temporal real-time quantitative PCR profiles of key genes suggest early ibuprofen interruption of crustacean eicosanoid metabolism, which appears to disrupt signal transduction affecting juvenile hormone metabolism and oogenesis.Combining molecular and organismal stress responses provides a guide to possible chronic consequences of environmental stress for population health. This could improve current environmental risk assessment by providing an early indication of the need for higher tier testing. Our study demonstrates the advantages of a systems approach to stress ecology, in which Daphnia will probably play a major role.Organismal stress responses have been studied for decades in ecology and ecotoxicology to establish the factors that limit species distributions and to investigate the effects of anthropogenic activities [1]. It was not until recently, however, that stress responses were investigated at the genomic level to illuminate underlying mechanisms [2,3]. Studying stress responses individually at just one level of biological organization yield little insight into how the organism deals with stress overall, but integration of responses at different levels promotes a holistic understanding of the whole system. Knowledge of the phenotypic consequences of stress as well as the genomic components (for instance, genes) that are induced or suppressed enables us to identify not only the mode of action (MOA) of the stressor but also which genomic components affect organismal growth, reproduction and survival, and thus populations. So, increased knowledge of the fundamental interactions between genome and phenotype should enable us to predict population stress responses better.In genomic non
The next evolutionary synthesis: from Lamarck and Darwin to genomic variation and systems biology
Jonathan BL Bard
Cell Communication and Signaling , 2011, DOI: 10.1186/1478-811x-9-30
Abstract: In the latter half of the twentieth century, the view of the process by which new species originated was based on meshing Darwinian variation and selection with work on population genetics and mutation. This view, the evolutionary synthesis, suggested that mutation within individuals led to genetic variation within a population; should a subgroup of that population become genetically isolated in a novel environment, a mix of unbalanced variation and new mutation within the subgroup would lead to new phenotypes appearing. In due course, one of these might reproduce better than the original phenotype so that it would take over and eventually lead to the appearance of a new species with a novel genotype [1].The enormous amount of molecular information that has emerged during the last couple of decades is making us review this synthesis, partly because we now know that the relationship between the phenotype and genotype is not as simple as previously assumed, partly because the genome is a richer, more complicated world than the scientists who put together the modern synthesis could ever have supposed and partly because there is data that does not fit comfortably within the synthesis. The two interesting and important books under review here set out to examine aspects of the state of evolutionary science now, the one taking an unashamedly contemporary position, the other starting from 200 years ago. Before discussing what they have to say, it is worth taking a look at their context by considering the state of evolutionary biology today.The evidence for evolution itself is robust as it comes from the three independent lines that each tells the same story: history (fossil record and isotope dating), morphology (taxonomic relationship and comparative embryology in living organisms - evolutionary change starts off as developmental change) and molecular sequence relationships. While the evolutionary synthesis is of course compatible with evolution, the evidence to support it
Quantum physics meets biology  [PDF]
Markus Arndt,Thomas Juffmann,Vlatko Vedral
Physics , 2009,
Abstract: Quantum physics and biology have long been regarded as unrelated disciplines, describing nature at the inanimate microlevel on the one hand and living species on the other hand. Over the last decades the life sciences have succeeded in providing ever more and refined explanations of macroscopic phenomena that were based on an improved understanding of molecular structures and mechanisms. Simultaneously, quantum physics, originally rooted in a world view of quantum coherences, entanglement and other non-classical effects, has been heading towards systems of increasing complexity. The present perspective article shall serve as a pedestrian guide to the growing interconnections between the two fields. We recapitulate the generic and sometimes unintuitive characteristics of quantum physics and point to a number of applications in the life sciences. We discuss our criteria for a future quantum biology, its current status, recent experimental progress and also the restrictions that nature imposes on bold extrapolations of quantum theory to macroscopic phenomena.
Comparative Systems Biology Reveals Allelic Variation Modulating Tocochromanol Profiles in Barley (Hordeum vulgare L.)  [PDF]
Rebekah E. Oliver, Emir Islamovic, Donald E. Obert, Mitchell L. Wise, Lauri L. Herrin, An Hang, Stephen A. Harrison, Amir Ibrahim, Juliet M. Marshall, Kelci J. Miclaus, Gerard R. Lazo, Gongshe Hu, Eric W. Jackson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096276
Abstract: Tocochromanols are recognized for nutritional content, plant stress response, and seed longevity. Here we present a systems biological approach to characterize and develop predictive assays for genes affecting tocochromanol variation in barley. Major QTL, detected in three regions of a SNP linkage map, affected multiple tocochromanol forms. Candidate genes were identified through barley/rice orthology and sequenced in genotypes with disparate tocochromanol profiles. Gene-specific markers, designed based on observed polymorphism, mapped to the originating QTL, increasing R2 values at the respective loci. Polymorphism within promoter regions corresponded to motifs known to influence gene expression. Quantitative PCR analysis revealed a trend of increased expression in tissues grown at cold temperatures. These results demonstrate utility of a novel method for rapid gene identification and characterization, and provide a resource for efficient development of barley lines with improved tocochromanol profiles.
Systems Biology — the Broader Perspective  [PDF]
Jonathan Bard
Cells , 2013, DOI: 10.3390/cells2020414
Abstract: Systems biology has two general aims: a narrow one, which is to discover how complex networks of proteins work, and a broader one, which is to integrate the molecular and network data with the generation and function of organism phenotypes. Doing all this involves complex methodologies, but underpinning the subject are more general conceptual problems about upwards and downwards causality, complexity and information storage, and their solutions provide the constraints within which these methodologies can be used. This essay considers these general aspects and the particular role of protein networks; their functional outputs are often the processes driving phenotypic change and physiological function—networks are, in a sense, the units of systems biology much as proteins are for molecular biology. It goes on to argue that the natural language for systems-biological descriptions of biological phenomena is the mathematical graph (a set of connected facts of the general form [process] (e.g., [activates] ). Such graphs not only integrate events at different levels but emphasize the distributed nature of control as well as displaying a great deal of data. The implications and successes of these ideas for physiology, pharmacology, development and evolution are briefly considered. The paper concludes with some challenges for the future.
Gene expression and the evolution of phenotypic diversity in social wasps
Eric A Hoffman, Michael AD Goodisman
BMC Biology , 2007, DOI: 10.1186/1741-7007-5-23
Abstract: We constructed 11 different cDNA libraries derived from various developmental stages and castes of Vespula squamosa. Comparisons of overall expression patterns indicated that gene-expression differences distinguishing developmental stages were greater than expression differences differentiating sex or caste. Furthermore, we determined that certain sets of genes showed similar patterns of expression in the same phenotypic forms of different species. Specifically, larvae upregulated genes related to metabolism and genes possessing structural activity. Surprisingly, our data indicated that at least a few specific gene functions and at least one specific gene family are important components of caste differentiation across social insect taxa.Despite research on various aspects of development originating from model systems, growth in understanding how development is related to phenotypic diversity relies on a growing literature of contrasting studies in non-model systems. In this study, we found that comparisons of patterns of gene expression with model systems highlighted areas of conserved and convergent developmental evolution across diverse taxa. Indeed, conserved biological functions across species implicated key functions related to how phenotypes are built. Finally, overall differences between social insect taxa suggest that the independent evolution of caste arose via distinct developmental trajectories.A fundamental goal of the burgeoning field of evolutionary developmental biology is to understand how differences in gene expression contribute to phenotypic diversity. Phenotypic plasticity, the ability of a single genotype to produce alternate forms of morphology, physiology or behavior in response to environmental conditions [1-3], provides a unique opportunity to investigate environmental influence on gene expression. Phenotypic plasticity is taxonomically widespread and usually results in continuous phenotypic variation [2,4]. However, some organisms exhibit p
Systems Biology  [cached]
Halil Kasap,Percin Pazarci,Mehmet Ali Erkoc
Arsiv Kaynak Tarama Dergisi , 2010,
Abstract: Systems biology is a newly emerged and multi-disciplinary study field that aims to understand the living organisms as complex, interacted and integrated networks of genes, proteins and biochemical reactions unlike the classical biology that have a reductionist approach. Instead of examining the proteins, genes and metabolic pathways separately like genetics, biology or biochemistry do, this study field accepts a new holistic approach which assumes that all the elements are pieces of a whole and they work by interacting with each other. This study field consists of the integration of genomics, transcriptomics, proteomics, metabolomics, glycomics, interactomics, fluxomics and bioinformatics. Systems biology quantifies the data gathered from these disciplines by making mathematical models and thus, it creates living system models by using computers and obtains information about the whole system. [Archives Medical Review Journal 2010; 19(1.000): 25-35]
Phenotypic Variation in Dysferlinopathy  [PDF]
Munevver CELIK,Hulya ERTASOGLU
Journal of Neurological Sciences , 2009,
Abstract: Mutations in the dysferlin gene cause distinct phenotypes of muscular dystrophy known by the term “dysferlinopathy”. Nowadays, four subtypes of dysferlinopathies have been established: limb-girdle muscular dystrophy 2B (LGMD 2B), Miyoshi myopathy (MM), distal anterior compartment type and scapuloperoneal type.We report a girl with dysferlinopathy with an unusual involvement of muscles in lower extremities and her brother whose symptoms started after the diagnosis of his sister.Both of them had lower limb weakness, marked elevation of serum creatine kinase (CK) levels and myopathic patterns in electromyography (EMG). Muscle biopsy of the girl who was diagnosed as having dysferlinopathy disclosed dystrophic changes and an absence of dysferlin. She had both proximal and distal weakness of the lower limbs presented in a 5-year-period. However her brother had difficulty only in foot dorsiflexion at the beginning of the symptoms.In conclusion, phenotypic variability, particularly at onset is one of the features of dysferlinopathies. To recognize and distinguish them from polymyositis is important to protect the patients from unnecessary treatment modalities. Recent imaging studies indicate that the pattern of muscular involvement is essentially uniform when both symptomatic and presymptomatic involvement is considered.
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