7th International Symposium on Networks in Bioinformatics

Program overview

Note that due to canceled flights two of Friday's keynote speakers (Anthony Bertucci and Tomer Shlomi) will not be able to come but we found two excellent speakers (Johannes Jaeger and Bas Teusink) willing to replace them. Thursday's program promises to be unaffected by volcanic ash!

Wednesday, April 21

• 19.00: Dinner for organisation and keynote speakers at: Indrapura, Rembrandtplein 42, 1017 CV Amsterdam, phone: +31 (0)20 623 73 29
  

Thursday, April 22

Friday, April 23

Keynote speakers

Dr. Steffen Klamt Structural and Functional Analysis of Cellular Networks Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg Germany

Qualitative modeling of cellular signaling networks: concepts, algorithms and application Abstract A central goal of systems biology is the construction of predictive models of cellular networks. Bio-molecular networks of moderate size have been modeled successfully in a quantitative way based on differential equations. In large-scale networks, knowledge of mechanistic details and kinetic parameters is often too limited to allow for the set-up of predictive quantitative models. In my talk I will present methods for qualitative and topology-based analysis of cellular signal transduction networks based on two different (but strongly related) formalisms for representing signaling networks: interaction graphs and logical networks. Interaction graphs (signed directed graphs) allow us to identify e.g. signaling paths, feedback loops or global causal dependencies. Based on these structural features one can make qualitative predictions (ups and downs) on the effect of perturbations giving us a valuable tool to detect inconsistencies between knowledge and measured data. Logical or Boolean models can be derived from interaction graphs by constraining the logical combination of edges. Using a hypergraphical representation of Boolean networks and introducing some novel techniques for their analysis we made this qualitative modeling approach also amenable to large-scale signaling networks. These techniques include qualitative simulation of stimulus-response experiments and the identification of proper intervention strategies enforcing or repressing a particular behavior. Recently we introduced a novel method to transform Boolean networks into a system of differential equations which may be used to study essential dynamic features of the network. I will also discuss algorithmic problems related to the analysis of interaction graphs (e.g. computation of shortest positive/negative paths) and logical networks (e.g. computation of minimal intervention sets). Practical application examples - including a large-scale model of EGF signaling - demonstrate that our methods deliver verifiable predictions and hypotheses on network function driving the iterative cycle between experiment and modeling.

Dr .Bas Teusink Department of Molecular Cell Physiology Free University Amsterdam The Netherlands

Understanding metabolic strategies through optimisation approaches Abstract Systems Biology aims at understanding the behaviour of biological systems most often, but not exclusively, at the cellular level on the basis of the properties of the biological components and their interactions. This is a dauntingly complex challenge, even though we have all the genetic components at hand, and we can increasingly more accurately measure the states variables of the cell, from genes, transcripts, and proteins, to fluxes and metabolites. One of the problems is that we have to reverse-engineer the function of the networks on the basis of measured data. What makes biology so unique, however, is that the systems under study are the result of evolution: all the functions we infer can and ultimately should be assessed in terms of fitness. This provides a purpose to biological systems that can be exploited in our reverse-engineering challenges. In this lecture I will make use of this property of life by mapping fitness to specific function, and function to design. I will illustrate this by focussing on the regulatory properties and evolution of metabolic networks, and imposing functions such as homeostasis, robustness and flux or yield maximization on these networks. Model predictions will subsequently be compared to experimental data, making use of laboratory-based (micro)evolution of microorganisms.

Dr. Tali Raveh-Sadka Segal lab of Computational Biology Weizmann Institute of Science Rehovot Israel

Predicting Expression Patterns From Sequence – Mechanistic Models For Transcriptional Control Abstract The establishment of complex expression patterns at precise times and locations is key to most biological processes, yet our understanding of the underlying transcriptional regulation is still limited. In my talk I will present two works aimed at uncovering the mechanistic principles that form the basis for transcriptional control. First, I will present our thermodynamic modeling framework for predicting expression patterns as a function of the regulatory sequence and of the binding-site preferences and expression of participating transcription factors. I will discuss its application to the intricate process of Drosophila melanogaster segmentation and show that our ability to predict expression in this system demonstrates that much of the positional information is encoded in the regulatory sequence and in the input factor distribution. In addition, I will show that further analysis of our predictions can be used to extract some of the design principles of transcriptional control in this system. Finally, I will present results obtained from an experimental system in yeast that was specifically developed in our lab to discover the mapping between DNA sequence and the transcriptional output, and use them to explore possible extensions of our modeling framework to include the effects of nucleosomes on transcriptional regulation.

Dr. Katy Wolfsencroft School of Computer Science University of Manchester Manchester UK

SysMO-DB: Sharing and Exchanging Data and Models in Systems Biology Abstract SysMO-DB is a web-based exchange environment for scientists to share and exchange Systems Biology data and models. It was designed to hold the research outcomes from the SysMO consortium (Systems Biology of Microorganisms), but the principles and methods employed could be generally applicable to Systems Biology research. SysMO-DB is composed of the SysMO SEEK and the SysMO JERM. The SEEK is a Yellow Pages and assets catalogue, describing who holds what resources and where they can be accessed. It is the main user interface to the system and links out to data, models, protocols and analysis methods hosted by individual projects. The JERM (“Just Enough Results Model”) is the underlying model for understanding the structure and content of assets, and extracting them from their source. A JERM for any one type of data (i.e. microarray data, or metabolomic data) is the minimum data schema that the SysMO projects agree to share. In addition, SysMO-DB provides integrated access to external resources, such as the model simulation tool from JWS Online. SysMO-DB is a light-touch approach to integration, allowing scientists to associate models and data in the context of experiments and the investigations they are a part of. Scientists can browse data and models, run simulations and further analyses on model predictions with data discovered through the SEEK. In this talk I will describe SysMO-DB and its support of the interaction between data and models in Systems Biology.

Prof. dr. Yaochu Jin Honda Research Institute Offenbach Germany

A fitness-independent evolvability measure for evolutionary developmental systems Abstract Evolvability refers to the organisms ability to create heritable new phenotypes that potentially facilitate the organism's survival and reproduction. In this paper, a general evolvability measure for a computational model of evolutionary development is proposed. The measure is able to quantify individuals' evolvability, including robustness and innovation, independent of the fitness function of the evolutionary system. Empirical studies are performed to check the evolvability of individuals in in silico evolution of oscillatory behavior using the proposed evolvability measure. Our preliminary results suggest that evolvability of the developmental system can evolve without an explicit selection pressure on evolvability, confirming findings revealed in other artificial evolutionary systems.

Dr Yulia Kraus Dept. of Evolutionary Biology Moscow State University Moscow Russia Department of Molecular Evolution and Development Faculty of Life Sciences University of Vienna Vienna Austria

Morphogenetic movements in the gastrulation of cnidarians: an ultrastructural study Abstract Cnidaria are the simple metazoan animals, consisting of only two cell layers: the outer ectoderm and the inner endoderm. A striking feature of this phylum is the high degree of developmental diversity, that can be observed at different time points of the cnidarian early development. Interestingly, the different developmental pathways successfully converge to form the morphologically conserved body plans of a planula larva and a polyp. It is known that different Cnidaria species display all modes of gastrulation known from high Metazoans: invagination, unipolar and multipolar ingression, two types of delamination and epiboly. So, what are the ultrastructural bases of these morphogenetic movements? To at least partly answer this question, we studied the changes of cell shape, the cellular behavior and the ultrastructure associated with the successive stages of gastrulation in the sea anemone Nematostella vectensis and in the colonial hydroid Clytia hemispaerica. Nematostella gastrulates by invagination of a pre-endodermal plate consisting of cells undergoing epithelial – mesenchymal transition and acquiring the “bottle” shape (Kraus, Technau. 2006; Magie et al., 2007). Ultrastructural study revealed several force-generating mechanisms, all of which can, in principle, drive the primary invagination and the deepening of Nematostella blastopore: 1) contraction of the microfilamental network joining the pre-endodermal plate cells, 2) centripetal movements of blastopore lip marginal cells, 3) contraction of the microfilamental ring surrounding the blastopore, 4) coordinated changes in the shape of blastopore lip epithelial cells providing the involution of the blastopore lip. Interestingly, the same morphogenetic mechanisms have been tested in the morpho-dynamic models of invagination that were developed for higher metazoans (Davidson et al.,1995; Keller et al., 2003). Gastrulation in Clytia has been described as an ingression of the presumptive endoderm cells from the specialized oral territory established by the action of maternally localized determinants (Metschnikoff, 1886; Freeman, 1981; Momose, Houliston, 2007). We have shown that the ingression in Clytia not only facilitates the formation of the endoderm, but also generates forces that shape the embryo in the course of gastrulation (Kraus et al., 2009).The behavior of the ingressed cells seems to be highly coordinated. They intercalate inside the blastocoel, aligning as layers. The endodermal cells migrate towards the blastocoel wall and also aborally as streams, in which cells are oriented end-to-end and side-to-side. We suppose that this coordinated cell behavior accounts for the changes in the embryonic morphology, such as the shrinking of the oralmost territory and the sharpening of the oral pole. The morphogenetic movements described here are only few examples out of a great variety of morphogenetic processes that can be observed in the different cnidarian species during gastrulation. So, Cnidaria represent a perfect phylum for anyone who wishes to formulate a biomechanical model of gastrulation.

Dr. Frederic Marin Biogeosciences University of Dijon Dijon France frederic.marin@u-bourgogne.fr

Shell formation in mollusks: molecular and evolutionary aspects Abstract For a decade, the field of molluscan shell biomineralization has accomplished remarkable progresses. The most recent advances deal more particularly with the structure of shell biominerals at the nanoscale, and with the identification of an increasing number of shell matrix protein components. Although the organic matrix represents usually less than 5% of the shell weight, it is however the major component that controls different aspects of the shell formation process. Until recently, the classical paradigm was to consider that the control of shell synthesis at the biocrystal scale was performed primarily by two mechanisms: crystal nucleation and growth inhibition. New concepts and emerging models try now to translate a more complex and dynamic reality, which is remarkably illustrated by the wide variety of shell proteins, characterized in the last few years (Marin et al., 2008). These proteins cover a broad spectrum of pI, from very acidic to very basic. The primary structure of a number of them is composed of different domains, suggesting that these proteins are multifunctional. Some of them exhibit enzymatic activities. Others may be involved in cell signalling. Some others have remarkable crystal-binding properties, and may even have an effect at the level of crystal lattice (Pokroy et al., 2006). Today, the extra-cellular calcifying shell matrix appears as a whole integrated system, which regulates protein-mineral and protein-protein interactions as well as feedback interactions between the biominerals and the calcifying epithelium that synthesized them. Marin, F., Luquet, G., Marie, B., and Medakovic, D., 2008. Curr. Topics Dev. Biol., 80, 209-276. Pokroy, B., Fitch, A. N., Marin, F., Kapon, N., Adir, N., and Zolotoyabko, E., 2006. J. Struct. Biol., 155, 96-103.

Dr. Johannes Jaeger Centre for Genomic Regulation Barcelona Spain
Regulation of gene expression in Drosophila Abstract to be announced

Presentation abstracts

Towards system level modeling of functional modules and context-specific pathways using genome-scale data.
Contributed speaker: Tom Michoel
Division of Bioinformatics and Systems Biology, Department of Plant Systems Biology, VIB, Ghent University, Belgium
Abstract

Maintaining optimal network functions in dynamic environments
Contributed speaker: Jan Berkhout
Vrije Universiteit, Amsterdam, the Netherlands
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Collaboration based Function Prediction in Protein-Protein Interaction networks
Contributed speaker: Hossein Rahmani
Leiden Institute of Advanced Computer Science, Universiteit Leiden, the Netherlands
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Recovering gene networks using l1 and l0 penalties
Contributed speaker: Johan De Rooi
Department of Bioinformatics, Erasmus Medical Centre, Rotterdam, the Netherlands
Abstract

Variation and canalization of gene expression in the Drosophila blastoderm
Contributed speaker: Maria Samsonova
Department of Computational Biology, Center for Advanced Studies, St.Petersburg State Polytechnical University, Russia
Abstract

The inheritance procedure: multiple testing of tree-structured hypotheses
Contributed speaker: Jelle J. Goeman
Medical Statistics and Bioinformatics, LUMC, Leiden, the Netherlands
Abstract

Mutational robustness of gene regulatory networks: interplay between transcription factor - target gene and protein-protein interactions
Contributed speaker: Aalt-Jan van Dijk
Applied Bioinformatics, PRI, Wageningen UR, Wageningen, The Netherlands
Abstract

Link and Node Prediction in Metabolic Networks with Probabilistic Logic
Contributed speaker: Fabrizio Costa
Department of Computer Science, Katholieke Universiteit Leuven, Belgium
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Stochastic simulation of gene regulatory states
Contributed speaker: David van Dijk
Computational Science, University of Amsterdam, the Netherlands
Abstract

Integration of human metabolic pathway databases: a critical assessment
Contributed speaker: Miranda Stobbe
Bioinformatics Laboratory, Academic Medical Center, Amsterdam,the Netherlands
Abstract

Spatiotemporal integration of signaling networks regulating pollen tube growth
Contributed speaker: Laura Zonia
University of Amsterdam, Swammerdam Institute for Life Sciences, Amsterdam, the Netherlands
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Population genomics of bacteria and yeast
Contributed speaker: Michael G. Sadovsky
Institute of computational modelling of SD RAS, Russia
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The reaction-dfifusion-mobility model for protein concentration dynamics
Contributed speaker: Alexander Samsonov
The Ioffe Physical Technical Institute of the Russian Academy of Sciences, St. Petersburg, Russia
Abstract

CaBioMinDB, a database for the proteins of CaCO3 mineralized tissues: further application to the shell proteins of the freshwater mussel Unio pictorum
Contributed speaker: Paula Ramos-Silva
CNRS Biogéosciences, Université de Bourgogne, Dijon, France
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Poster abstracts

Visualizing gene expression in transcription regulation and metabolic networks
Michel Westenberg
Department of Mathematics and Computer Science, TU Eindhoven, The Netherlands
Abstract

Information Capacity of Genomes
Anna A. Koval
Siberian Federal University
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Combinatorial Properties of Genomes
Evgeniya Temlyakova
Siberian Federal University
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A model of networks with structured nodes
Pierluigi Frisco
School of Math. and Comp. Sciences, Heriot-Watt University, Edinburgh, UK
Abstract

Systems biology analysis at VIB
Xin-Ying Ren
VIB - Department of Plant Systems Biology, Gent University, 9052 Gent, Belgium
Abstract