iViS (In Vivo - In Silico) - Grand Challenge Website

Author: Ronan Sleep
Date: 25 March 2004

Summary / Description:
The aim of the in Vivo - in Silico (iViS) Grand Challenge is to realise fully detailed, accurate and predictive models of some of the most studied life in biology. This note offers but one way of attacking this ambitious goal: there are certainly other - for example the many bottom-up projects world wide that are mapping various genomic regulatory networks. I propose a top-down approach, driven by the various phenomena discovered by experimental embryology. An augmented BSP-like (Bulk Synchronous Parallel) architecture is suggested as a starting point, with an added computational geometry step using potential field models of cell interactions.

Category - Keywords: Grand Challenge 1, iViS, lifeforms in silico, biological development.

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Authors: Ronan Sleep and Ioannis Elpidis
Date: February 2004

Summary / Description:
The life-sciences are advancing by leaps and bounds: hard on the heels of the human genome project come the Proteome and Metabolome projects, creating even more data to digest. We routinely use advanced graphics and simulation to design aeroplanes and build bridges: in this paper we argue that the time is right to attack the accurate modelling of the development of whole life forms. Such a model would initially serve as a 4-D integrated repository of knowledge, but as it becomes populated with increasingly detailed and accurate biological data, and as the simulation and graphics develop in fidelity, the model can be used to carry out in-silico experiments with increasing accuracy. We survey the previous and current approaches to providing a computational geometry framework for such models, and suggest a new approach.

Category - Keywords: iViS, life-sciences, soft-objects, computational geometry

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Author: Pankaj Agarwal
Date: 1995

Summary / Description:
In developmental biology, modeling and simulation play an important role in understanding cellular behavior. This article includes a review of the general models of development that are based on cellular interaction. Inspired by these models, we suggest a simple language, the Cell Programming Language (CPL), to write computer programs to describe this developmental behavior. These programs are an estimate of the minimal information needed to model realistically such developmental systems. Using these programs, it is possible to simulate and visualise cell behavior. We have employed CPL to model the following: aggregation in cellular slime mold in response to a chemotactic agent, cellular segregation and engulfment due to differential adhesion, and precartilage fomation in vertebrate limbs. We believe CPL is a useful tool for developing, understanding, and checking biological models.

Category - Keywords: Modeling, Simulation, General model of development, Cell interaction, Pattern formation, Morphogenesis, Programming Language.

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Author: Thomas Berleth and Steve Chatfield
Date: 2002

Summary / Description:
During embryogenesis a single cell gives rise to a functional multicellular organism. In higher plants, as in many other multicellular systems, essential architectural features, such as body axes and major tissue layers are established early in embryogenesis and serve as a positional framework for subsequent pattern elaboration. In Arabidopsis, the apical-basal axis and the radial pattern of tissues wrapped around it is already anatomically recognizable in very young embryos of approximately a hundred cells. This early axial pattern seems to provide a coordinate system for the embryonic initiation of shoot and root. Findings from genetic studies in Arabidopsis are revealing molecular mechanisms underlying the initial establishment of the axial core pattern and its subsequent elaboration into functional shoots and roots. The genetic programs operating in the early embryo organize functional cell patterns rapidly and reproducibly from minimal cell numbers. Understanding their molecular details could therefore greatly expand our ability to generate plant body patterns de novo, with important implications for plant breeding and biotechnology.

Category - Keywords: Arabidopsis, embryo defective mutants, embryo pattern formation, root meristem, shoot meristem, cell polarity.

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Authors: Kurt Fleischer and Alan H. Barr
Date: 1993

Summary / Description:
This paper presents a simulation framework and computational testbed for studying multicellular pattern formation. The approach combines several developmental mechanisms (chemical, mechanical, genetic, and electrical) known to be important for biological pattern formation. The mechanisms are present in an environment containing discrete cells which are capable of independent movement (cell migration). Experience with the testbed indicates that the interactions between the developmental mechanisms are important in determining multicellular and developmental patterns.

Each simulated cell has an artificial genome whose expression is dependent only upon its internal state and its local environment. The changes of each cell's state and of the environment are determined by piecewise continuous differential equations. The current two-dimensional simulation exhibits a variety of multicellular behaviors, including cell migration, cell differentiation, gradient following, clustering, lateral inhibition, and neurite outgrowth.

We plan to perform simulated evolution on developmental models as part of a long range goal to create artificial neural networks which solve problems in perception and control. The testbed is a step on the path towards this goal.

Category - Keywords: Simulated cell, Artificial genome, Multicellular pattern formation.

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Authors: Kouichi Takahashi, Kazunari Kaizu, Bin Hu and Masaru Tomita
Date: 2003

Summary / Description:
Many important problems in cell biology require the dense nonlinear interactions between functional modules to be considered. The importance of computer simulation in understanding cellular processes is now widely accepted, and a variety of simulation algorithms useful for studying certain subsystems have been designed. Many of these are already widely used, and a large number of models constructed on these existing formalisms are available. A significant computational challenge is how we can integrate such sub-cellular models running on different types of algorithms to construct higher order models.

A modular, object-oriented simulation metaalgorithm based on a discrete-event scheduler and Hermite polynomial interpolation has been developed and implemented. It is shown that this new method can efficiently handle many components driven by different algorithms and different timescales. The utility of this simulation framework is further demonstrated with a “composite” heatshock response model that combines the Gillespie- Gibson stochastic algorithm and deterministic differential equations. Dramatic improvements in performance were obtained without significant accuracy drawbacks. A multi-timescale demonstration of coupled harmonic oscillators is also shown.

Category - Keywords: Multi-cellular, Cell simulation, Timescale, Cell biology, E-Cell.

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Author: Gerd Jurgens
Date: 2001

Summary / Description:
Embryogenesis transforms the fertilized egg cell into a multicellular organism. In higher animals, the mature embryo is a miniature variant of the adult animal, and whatever changes may take place during post-embryonic development, they occur within the confines of the body organization established during embryogenesis. By contrast, higher plant embryogenesis generates a juvenile form, the seedling, which lacks most species-specific features of the adult plant. Post-embyonic development originates from two primary meristems, stem-cell systems that occypy opposite ends if the main body axis. The primary shoot meristem at the top end is the source of cells for the new organsm such as leaves, and secondary shoot meristems, including flowers. The primary root meristem at the bottom end produces cells for extension growth of the primary root. In addition, root branches are initiated from specific cell groups within the primary root. These primordia recapitulate radial patterning and root meristem establishment as occurs in embryogenesis. Thus, the considerable increase in architectural complexity during post-embryonic development is contingent upon the basic body organization laid down during embryogenesis.

Category - Keywords: Arabidopsis, Axis, Embryogenesis, Meristem, Polarity.

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Authors: Bjorn E. Oleson, Mark Moller, and Klaus Prank
Date: 2003

Summary / Description:Cells must be able to sense and respond to their environment, in particular to communicate with other cells. The exchange of information, called signal transduction, between and inside cells is essential for their survival. Modelling of cellular processes, such as signal transduction often involves the representation of biochemical reactions with very small numbers of molecules. Deterministic approaches to a continuous-variation in the concentrations of molecular species by using systems of coupled ordinary differential equations (ODE) fail. In order to correctly model the dynamics of cellular signalling, stochastic effects have to be taken into account. Stochastic simulations try to imitate biophysically and biochemically realistic processes by using computational methods. There have been already several attempts to use Monte Carlo simulations for the study of biochemical kinetics. However, these approaches possess a major problem. Although these algorithms are elegant and strait forward, the understanding of a model and its transformation to the simulation both become rather complicated. The user here has to handle with abstract parameters not easily found in the lab. In our computational approach we examine the important means by which cells communicate and work, using modelling and simulation of cellular behaviour, the interpretation of information transferred in as well as between cells, and the interpretation of signals they receive.

Category - Keywords: Stohastic Cell Simulation, Signal Transduction, Systems Biology, CAVE, Visualization

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Author: Masaru Tomita
Date: June 2001

Summary / Description:
Study of the cell will never be complete unless its dynamic behavior is understood. The complex behavior of the cell cannot be determined or predicted unless a computer model of the cell is constructed and computer simulation is undertaken. Rapid accumulation of biological data from genome, proteome, transcriptome and metabolome projects can bring us to the point where it is no longer purely speculative to discuss how to construct virtual cells in silico. This article describes attempts to construct whole cell models. The E-CELL project has completed a couple of virtual cell models, and computer simulations have revealed some biological surprises.

Category - Keywords: E-Cell project, Cell Models, Virtual Cells in Silico, Genome, Proteome.

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Author: Maria Louise Lantin
Date: November 1997

Summary / Description:
The ultimate goal of developmental biology is to discover how one cell with limited direct information can develop into a complex organism. Countless experiments have been done and several hypotheses have been put forward to explain the differentiation, migration, growth and division of cells in early plant and embryonic development. Mechanical, chemical and electrical mechanisms (and combinations of these) have been suggested as being responsible for the aforementioned cellular behavior. Through developmental models and computer simulations it is hoped that we can compliment traditional techniques and gain a better understanding of how these mechanisms interact with each other and influence cellular development.

Category - Keywords: Cell-cell communications, Cellular behavior, Differentiation, Morphogenesis

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Authors: Scott E. Fraser and Richard M. Harlang
Date: 7 January 2000

Summary / Description:
Most embryologists have beed drawn to the field by the beauty of the developing embryo and the mystery of its structure emerging from a single fertilized egg. The classic publications in the field of exprerimental embryology illustrate the powe of describing cell behavior and perturbing the embryo to test hypotheses of the underlying mechanisms. This tight coupling between observation, hypothesis, and perturbation has extracted significant insights from relatively simple expreimental designs. Simple perturbation experiments designed to destroy the genetic information offered some of the first evidence that information in the chromosomes depended on intact DNA. Thus, the basic approach of the exprerimental embryologist has generated insights that are amazing in their accuracy and depth.

Category - Keywords: Molecular metamorphosis, Embryogenesis, Cell behavior, Fate maps, Diversification.

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Authors: Thomas Seidl and Hans-Peter Kriegel
Date: 1995

Summary / Description:
Applications in molecular biology more and more require geometric data management along with physicochemical data handling. Thus, 3D structures and surfaces of molecules become basic objects in molecular databases. We propose the neighborhood query on graphs such as molecular surfaces as a fundamental query class concerning topological information on patch adjacency. Furthermore, we suggest a patch-based data structure, called the TriEdge structure, first, to efficiently support neighborhood query processing, and second, to save space in comparison to common 2D subdivision data structures such as the quad-edge structure or the doubly-connected edge list. In analogy to the quad-edge structure, the TriEdge structure has an algebraic interface and is implemented via complex pointers. However, we achieve a reduction of the space requirement by a factor of four. Finally, we investigate the time performance of our prototype which is based on an object-oriented database management system.

Category - Keywords: 3D Molecular modeling, Spatial databases, Surface representation, Surfance approximation, Database systems in molecular biology.

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Authors: A. Frinkelstein, J. Hetherington, L. Li, O. Margoninski, P. Saffrey, R.Saymour and A. Warner
Date: 2004 ?

Summary / Description:
Systems biology is an important and higly demanding area of interdisciplinary science. We argue that, as discipline, computer science has much to contribute to meeting these demands. We outline what is meant by systems biology, and contrast it with bioinformatics. We then briefly review the computing contributions to the state-of-the-art. The paper uses a simple information model to outline the challenges for computer science in this new and largely uncharted area. An example is presented which illustrates the complexities that must be faced. We discuss modelling strategy and conclude by marking some staging posts for future progress.

Category - Keywords: Systems biology, Bioinformatics, Cell markup-language (CellML), Liver model, Heart model.

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Author: Richard Kennaway
Date: 2004

Summary / Description:
We describe an experiment in robot control, using a simulated six-legged robot. The robot, herein called Archy, is capable of standing, resisting disturbing forces, and walking over uneven terrain and up and down a staircase. It can continue to stand up and control its body position and orientation even when some legs are removed. The control systems are all simple PID controllers, with a couple of fuzzy controllers for navigating when walking.

Category - Keywords: Robotics, Walking robot, fuzzy controllers.

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Authors: Chiou-Hwa Yuh, Hamid Bolouri and Davidson Eric H.
Date: 20 March 1998

Summary / Description:
The genomic regulatory network that controls gene expression ultimately determines form and function in each species. The operational nature of the regulatory programming specified in cis-regulatory DNA sequence was determined from a detailed functional analysis of a sea urchin control element that directs the expression of a gene in the endoderm during development. Spatial expression and repression, and the changing rate of transcription of this gene, are mediated by a complex and extended cis-regulatory system. The system may be typical of developmental cis-regulatory apparatus. All of its activities are integrated in the proximal element, which contains seven target sites for DNA binding proteins. A quantitative computational model of this regulatory element was constructed that explicitly reveals the logical interrelations hard-wired into the DNA.

Category - Keywords: The category it is listed and a list of keywords

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Authors: Chiou-Hwa Yuh, Hamid Bolouri and Davidson Eric H.
Date: 20 March 1998

Summary / Description:
The genomic regulatory network that controls gene expression ultimately determines form and function in each species. The operational nature of the regulatory programming specified in cis-regulatory DNA sequence was determined from a detailed functional analysis of a sea urchin control element that directs the expression of a gene in the endoderm during development. Spatial expression and repression, and the changing rate of transcription of this gene, are mediated by a complex and extended cis-regulatory system. The system may be typical of developmental cis-regulatory apparatus. All of its activities are integrated in the proximal element, which contains seven target sites for DNA binding proteins. A quantitative computational model of this regulatory element was constructed that explicitly reveals the logical interrelations hard-wired into the DNA.

Category - Keywords: The category it is listed and a list of keywords

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