Indentifying sub-network functional modules in protein undirected networks

Protein networks are usually used to describe the interacting behaviours of complex biosystems. Bioinformatics must be able to provide methods to mine protein undirected networks and to infer subnetworks of interacting proteins for identifying relevant biological pathways. Here we present FunMod an innovative Cytoscape version 2.8 plugin able to identify biologically significant sub-networks within informative protein networks, enabling new opportunities for elucidating pathways involved in diseases. Moreover FunMod calculates three topological coefficients for each subnetwork, for a better understanding of the cooperative interactions between proteins and discriminating the role played by each protein within a functional module. FunMod is the first Cytoscape plugin with the ability of combining pathways and topological analysis allowing the identification of the key proteins within sub-network functional modules

Alzheimer’s Disease under the Purview of Graph Theory Centric Genetic Networks

Notice that the synapsis of brain is a form of communication. As communication demands connectivity, it is not a surprise that "graph theory" is a fastest growing area of research in the life sciences. It attempts to explain the connections and communication between networks of neurons. Alzheimer’s disease (AD) progression in brain is due to a deposition and development of amyloid plaque and the loss of communication between nerve cells. Graph/network theory can provide incredible insights into the incorrect wiring leading to memory loss in a progressive manner. Network in AD is slanted towards investigating the intricate patterns of interconnections found in the pathogenesis of brain. Here, we see how the notions of graph/network theory can be prudently exploited to comprehend the Alzheimer’s disease. We begin with introducing concepts of graph/network theory as a model for specific genetic hubs of the brain regions and cellular signalling. We begin with a brief introduction of prevalence and causes of AD followed by outlining its genetic and signalling pathogenesis. We then present some of the network-applied outcome in assessing the disease-signalling interactions, signal transduction of protein-protein interaction, disturbed genetics and signalling pathways as compelling targets of pathogenesis of the disease.</em

The functional network in predictive biology : predicting phenotype from genotype and predicting human disease from fungal phenotype

textThe ability to predict is one of the hallmarks of successful theories. Historically, the predictive power of biology has lagged behind disciplines like physics because the biological world is complex, challenging to quantify, and full of exceptions. However, in recent years the amount of available data has expanded exponentially and biological predictions based on this data become a possibility. The functional gene network is a quantitative way to integrate this data and a useful framework for making biological predictions. This study demonstrates that functional networks capture real biological insight and uses the network to predict both subcellular protein localization and the phenotypic outcome of gene knockouts. Furthermore, I use the functional network to evaluate genetic modules shared between diverse organisms that lead to orthologous phenotypes, many that are non-obvious. I show that the successful predictions of the functional network have broad applicability and implications that range from the design of large-scale biological experiments to the discovery of genes with potential roles in human disease.Institute for Cellular and Molecular Biolog

Transcriptome signature of the adult mouse choroid plexus

<p>Abstract</p> <p>Background</p> <p>Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP) transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid.</p> <p>Methods</p> <p>This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions.</p> <p>Results</p> <p>We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier.</p> <p>Conclusions</p> <p>Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.</p

Unravelling the proteome of chromatin bound RNA polymerase II using Proteome-ChIP in murine stem cells

Regulation of gene expression is critical to govern distinct transcriptional programs for a cell type, lineage specification and developmental stage. Transcription is the first step in gene expression wherein RNA Polymerase II (RNAPII) transcribes protein-coding genes. Transcription is a highly coordinated process that involves a range of chromatin interactions including transcription machinery, chromatin remodellers and co-transcriptional RNA processing. Embryonic stem (ES) cells are pluripotent, self-renewing cells that can differentiate to give rise to all lineages making them an invaluable tool to study early development and in therapy. Genome-wide analysis in murine mES cells has identified 30% of known genes harbouring bivalent chromatin modifications along with repressive Polycomb complexes and a novel variant of RNAPII (modified as S5p+S7p-S2p-) with mechanistic implications in stem cell pluripotency, differentiation potential and lineage specification. To explore chromatin composition associated with different variants of RNAPII, I developed an unbiased method, ‘Proteome-ChIP’ (pChIP) wherein crosslinked chromatin is purified by immunoprecipitation followed by protein extraction and identification by Mass Spectrometry. Using an unbiased comprehensive experimental strategy and a novel systems biology approach, I qualitatively and quantitatively dissect the proteome composition and dependencies on RNAPII modifications during different stages of the transcription cycle. The work done in this thesis provides an invaluable resource of RNAPII chromatin interactions. We identify known and novel components of the co-transcriptional machinery, chromatin remodelling and RNA processing machinery. The work also uncovers novel processes associated with unusual RNAPII (S5p+S7p-S2p-) including DNA replication, Polycomb proteins and chromatin remodellers; many of these processes critical for stem cell viability and regulation. Extending the RNAPII-pChIP analysis on low complexity samples by Native-pChIP and Gradient-pChIP highlights the versatility of robustness of our method. The work described in this sheds light on regulatory chromatin processes specific to mES cells, which informs our understanding of stem cell biology and reprogramming

De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.

Neurodevelopmental and psychiatric disorders are a highly disabling and heterogeneous group of developmental and mental disorders, resulting from complex interactions of genetic and environmental risk factors. The nature of multifactorial traits and the presence of comorbidity and polygenicity in these disorders present challenges in both disease risk identification and clinical diagnoses. The genetic component has been firmly established, but the identification of all the causative variants remains elusive. The development of next-generation sequencing, especially whole exome sequencing (WES), has greatly enriched our knowledge of the precise genetic alterations of human diseases, including brain-related disorders. In particular, the extensive usage of WES in research studies has uncovered the important contribution of de novo mutations (DNMs) to these disorders. Trio and quad familial WES are a particularly useful approach to discover DNMs. Here, we review the major WES studies in neurodevelopmental and psychiatric disorders and summarize how genes hit by discovered DNMs are shared among different disorders. Next, we discuss different integrative approaches utilized to interrogate DNMs and to identify biological pathways that may disrupt brain development and shed light on our understanding of the genetic architecture underlying these disorders. Lastly, we discuss the current state of the transition from WES research to its routine clinical application. This review will assist researchers and clinicians in the interpretation of variants obtained from WES studies, and highlights the need to develop consensus analytical protocols and validated lists of genes appropriate for clinical laboratory analysis, in order to reach the growing demands

Comparative genomics and systems biology of environmental stress responses relevant to fungal virulence

Imperial Users onl

Community and Identity in Contemporary Technosciences

This open access edited book provides new thinking on scientific identity formation. It thoroughly interrogates the concepts of community and identity, including both historical and contemporaneous analyses of several scientific fields. Chapters examine whether, and how, today’s scientific identities and communities are subject to fundamental changes, reacting to tangible shifts in research funding as well as more intangible transformations in our society’s understanding and expectations of technoscience. Authors: Karen Kastenhofer, Susan Molyneux-Hodgson, Clemens Blümel, Bettina Bock von Wülfingen, Béatrice Cointe, Carlos Cuevas-Garcia, Sarah R Davies, Alexander Degelsegger-Márquez, Juliane Jarke, Pierre-Benoît Joly, Marianne Noël, Benjamin Raimbault, Andrea Schikowitz, Sarah M. Schönbauer, Inga Ulnicane-Ozolina, Caitlin D. WylieDer vorgelegte Open Access Band befasst sich mit Identität und Gemeinschaft in den TechnoWissenschaften. Er widmet sich wesentlichen soziologischen Konzepten und präsentiert sowohl historische, als auch aktuelle Fallbeispiele, darunter Supramolekulare Chemie, Synthetische Biologie, Nanotechnologie und Nachhaltigkeitsforschung. AutorInnen: Karen Kastenhofer, Susan Molyneux-Hodgson, Clemens Blümel, Bettina Bock von Wülfingen, Béatrice Cointe, Carlos Cuevas-Garcia, Sarah R Davies, Alexander Degelsegger-Márquez, Juliane Jarke, Pierre-Benoît Joly, Marianne Noël, Benjamin Raimbault, Andrea Schikowitz, Sarah M. Schönbauer, Inga Ulnicane-Ozolina, Caitlin D. Wyli