biological systems simulations based on negative feedback european union european regional...
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BIOLOGICAL SYSTEMS SIMULATIONS BASED ON NEGATIVE FEEDBACK
EUROPEAN UNIONEUROPEAN REGIONAL
DEVELOPMENT FUND
The work was co-funded by the European Regional Development Fund as part of the Innovative Economy program.
Jakub Wach3, Marian Bubak1,3, Leszek Konieczny2, Irena Roterman-Konieczna2
1AGH University of Science and Technology, Department of Computer Science, Kraków, Poland
2Jagiellonian University, Department of Bioinformatics and Telemedicine, Kraków, Poland
3Academic Computer Centre Cyfronet AGH, Kraków, Poland
http://dice.cyfronet.pl
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PROBLEM DESCRIPTION
Biological system Anything alive (enzyme, virus, cell, ….) Mulitple levels – from a single enzyme to whole organism
Need for simulation Novel treatments Insight into details (structure and function preciction)
Existing simulation methods Approximate (based on PDEs) Precise (Stanford cell model)
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NFS APPROACHThe idea L. Konieczny, I. Roterman, P. Spolnik : “Systems
biology” Model function, not structure Use negative-feedback systems (NFSs), simplest
regulator as building blocks
Negative Feedback System Effector
Delivers a product Output regulated by Receptor
Receptor Delivers signal regulating Effector Signal output is regulated by product level
Effector
Substrate
Outflow
Receptor
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NFS APPROACH - SYSTEMS Biological system – composition of building blocks Organized Systems – OS – composition of connected NFSs
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OS - COOPERATION Cooperation connection
Product of one NFS is substrate of another one Receptor is not aware of the change – it’s a local
(Effector) relation Example – enzymatic cascade, where one
enzyme delivers substrate to another, e.g. glycolysis
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OS - COORDINATION Coordiation connection
One NFS can change regulation threshold of another NFS Whole NFS is affected – it’s a global (Receptor) relation Example – allosteric control of enzymes
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OS – HIERARCHY Component hierarchy
One NFS can be coupled with a Receptor
Higher – level NFS is created this way Multiple „nesting” levels possible Example – hormonal regulation
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APPLICATION
Multiple modules available
Implements OS model with all of the relations Allows both bounded (cooperation) and unbounded (unlimited source)
NFSs Allows space-time constraints by introducing delay parameter Simple iterative simulation algorithm Sophisticated, real product diffusion model
http://crick.cm-uj.krakow.pl:8080/nfs/
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APPLICATION - PLAYGROUND
JSON definition of an OS Graphical parameters editor
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APPLICATION - PLAYGROUND
Real time OS model visualization in SVG (already presented)
Simulation run results charts Archivable and exportable
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APPLICATION - MANAGEMENT
Provides exercise management Allows for creating, editing and deleting
exercises Allows for user (student) assignment Allows date / time constraints for
exercises
Provides task management Allows for OS definition for a task User can add name and description for a
task
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WORKFLOW INTEGRATION
Models can be very complex, even for typical scenarios Hundreds of parameters for optimization Search for appropriate structure and values