BioUML

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BioUML integrated platform for systems
biologyFrom gene regulatory networks to
modeling virtual cell and virtual physiological
human
Fedor Kolpakov Institute of Systems
BiologyNovosibirsk, Russia
Alexander Kel geneXplain GmbH,Wolfenbuettel,
Germany
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BioUML platform

• BioUML is an open source integrated platform for
  systems biology that spans the comprehensive
  range of capabilities including access to
  databases with experimental data, tools for
  formalized description, visual modeling and
  analyses of complex biological systems.
• Due to scripts (R, JavaScript) and workflow
  support it provides powerful possibilities for
  analyses of high-throughput data.
• Plug-in based architecture (Eclipse run time from
  IBM is used) allows to add new functionality
  using plug-ins.
• BioUML platform consists from 3 parts
• BioUML server provides access to biological
  databases
• BioUML workbench standalone application.
• BioUML web edition web interface based on AJAX
  technology

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BioUML main features

• Supports access to main biological databases
• catalolgs Ensembl, UniProt, ChEBI, GO
• pathways KEGG, Reactome, EHMN, BioModels,
  SABIO-RK, TRANSPATH, EndoNet, BMOND
• Supports main standards used in systems biology
  SBML, SBGN, CellML, BioPAX, OBO, PSI-MI
• database search
• full text search using Lucene engine
• graph search
• graph layout engine
• visual modeling
• simulation engine supports (ODE, DAE, hybrid,1D
  PDE)
• composite models
• agent based modeling
• parameters fitting
• genome browser (supports DAS protocol, tracks
  import/export)
• data analyses and workflows specialized
  plug-ins for microarray analysis, integration
  with R/Bioconductor, JavaScript support,
  interactive script console.

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BioUML workbench
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BioUML web edition
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BioUML web editiondedicated Amazon EC2 server
http//79.125.109.165/bioumlweb BioUML
workbenchhttp//79.125.109.165/bioumlweb/biouml-
install.jarPrerequisite Java
www.java.com/getjava/
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Notation
Entities
RNA Active monomer Inactive monomer Phosphoryla
ted protein
Heterodimer Homodimer Multimer
Reactions
Binary reaction
Complex reaction
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Text searchuniversal full text search engine
based on Apache Lucene technology
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Metaphor biological systems reconstruction as
solitaire (patience) game
Desk BioUML editor Solitaire biological
pathway Cards biological objects(genes,
proteins, lipids, etc.) Pack of cards
different biological databases
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Biomodels databaseSBGN Graph layoutVisual
modelling
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SBGN Process Description Diagram 1.1
Entity Pool Nodes
Auxiliary Units
Process Nodes
Connecting Arcs
process
consumption
unspecified entity
unit of information
uncertain process
state variable
production
simple chemical
omitted process
modulation
association
macromolecule
LABEL
marker
catalysis
clone markers
dissociation
nucleic acid feature
stimulation
LABEL
phenotype
LABEL
inhibition
perturbing agent
necessary stimulation
Container Node
source sink
multimers
Source EPN
logic arc
equivalence arc
compartment
Logical Operators
Reference Nodes
and operator
LABEL
or operator
complex
tag
submap
not operator
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Visual modeling
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Pane model parmaters
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Pane model variables
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Pane model variables
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Pane model simulation
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Reports (templates)
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Parameters fitting
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Main features

• Experimental data time courses or steady states
  expressed as exact or relative values of
  substance concentrations
• Different optimization methods for analysis
• Multi-experimentsfitting
• Constraint optimization
• Local/global parameters
• Parameters optimization using java script

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Comparison with COPASI (10,000 simulations)
Method BioUML (4 cores) BioUML (1 core) COPASI (1 core)
Evolutionary Programming 1 min 58,2sec 1 min 31,3 sec 1 min 16,6 sec
Particle swarm 7,1 sec 7,7 sec 6,9 sec 22,4 sec 15,3 sec 22,5 sec 1 min 32 sec 1 min 26,4 sec 1 min 07,1 sec
Stochastic Ranking Evolution Strategy 7,5 sec 7,47 sec 6,9 sec 23,4 sec 23,5 sec 22,2 sec 1 min 25,0 sec 1 min 5,6 sec 1 min 8,8 sec
Cellular genetic algorithm 7,7 sec 7,5 sec 7,2 sec 25,5 sec 22,1 sec 20,8 sec
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Parameters fitting user interface
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CD95L module and results of fitting its dynamics
to experimental data
Bentele M, 2004
Neumann L, 2010
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Genome browser
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Genome browser main features

• uses AJAX and HTML5 ltcanvasgt technologies
• interactive - dragging, semantic zoom
• tracks support
• Ensembl
• DAS-servers
• user-loaded BED/GFF/Wiggle files

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Data analysescollaboration reproducible
research
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JavaScript host objects allows to merge
R/Bioconductor and Java/BioUML worlds
R world
Java/BioUML world
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Analysis workflow
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JavaScript console
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Composite modelsPoster Modular Approach To
Modeling Of The Apoptosis MachineryAgent based
modelingPosterAgent based modelling plug-in
for BioUML platform
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Composite model of apoptosis (286 species, 684
reactions)
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CD95L module and results of fitting its dynamics
to experimental data
Bentele M, 2004
Neumann L, 2010
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Agent based model of arterial hypertension (blood
pressure regulation)
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• October 10 Tutorial 3 BioUML integrated
  platform for building virtual cell and virtual
  physiological human
• October 12, 16.20-16.40, Parallel sessionFedor
  Kolpakov Modular Approach To Modeling Of The
  Apoptosis Machinery
• October 11-12, poster session
• BioUML Integrated Platform for Building
  Virtual Cell and Virtual Physiological Human
• Modular Approach To Modeling Of The Apoptosis
  Machinery
• The Optimization Plug-in For The BioUML Platform
• Agent based modelling - plug-in for BioUML
  platform Numerical Analysis Of The Complex Model
  Of Human Cardio-Vascular System Using 1D
  Hemodynamic Model
• Stand of geneXplain GmbH company

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Acknowledgements

• Part of this work was partially supported by the
  grant
• European Committee grant ?037590 Net2Drug
• European Committee grant ?202272 LipidomicNet
• Integration and interdisciplinary grants ?16, 91
  of SB RAS.
• BioUML team
• Software developers Biologists
• Nikita Tolstyh Ilya Kiselev Ruslan Sharipov
• Tagir Valeev Elena Kutumova Ivan Yevshin
• Anna Ryabova Alexey Shadrin

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BioUML architecture
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Plug-in based architecture
A plug-in is the smallest unit of BioUML
workbench function that can be developed and
delivered separately into BioUML workbench. A
plug-in is described in an XML manifest file,
called plugin.xml. The parsed contents of plug-in
manifest files are made available
programmatically through a plug-in registry API
provided by Eclipse runtime. -
extension points are well-defined function points
in the system where other plug-ins can contribute
functionality. - extension is a
specific contribution to an extension point.
Plug-ins can define their own extension points,
so that other plug-ins can integrate tightly with
them.

• Plug-in
• plugin.xml
• Java jar files

• Plug-in
• plugin.xml
• Java jar files

• Plug-in
• plugin.xml
• etc.

Eclipse platform runtime (IBM)
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