Multiscale Modelling Project Fallot Tariq Abdulla December 2009.

Slides:



Advertisements
Similar presentations
Annotation of Gene Function …and how thats useful to you.
Advertisements

The bioinformatics of biological processes The challenge of temporal data Per Kraulis Avatar Software AB.
Biological pathway and systems analysis An introduction.
Prof. Carolina Ruiz Computer Science Department Bioinformatics and Computational Biology Program WPI WELCOME TO BCB4003/CS4803 BCB503/CS583 BIOLOGICAL.
Simulation-based model checking approach to cell fate specification during C. elegans vulval development by HFPNe Chen LI Masao Nagasaki Kazuko Ueno Satoru.
University of Sheffield Modelling Tissue Development Rod Smallwood, Mike Holcombe, Sheila Mac Neil, Rod Hose, Richard Clayton.
GOAT: The Gene Ontology Annotation Tool Dr. Mike Bada Department of Computer Science University of Manchester
Models and methods in systems biology Daniel Kluesing Algorithms in Biology Spring 2009.
Systems Biology Existing and future genome sequencing projects and the follow-on structural and functional analysis of complete genomes will produce an.
Petri net modeling of biological networks Claudine Chaouiya.
Systems Modelling of EMT Cell Signalling Pathways in Heart Valve Development Tariq Abdulla 1, Ryan Imms 1, Jean-Marc Schleich 2 and Ron Summers 1 VPH 2010.
Multiscale Information Modelling for Heart Morphogenesis Tariq Abdulla 13 th IMEKO TC1-TC7 Joint Symposium 02/09/2010.
XML Documentation of Biopathways and Their Simulations in Genomic Object Net Speaker : Hungwei chen.
Fungal Semantic Web Stephen Scott, Scott Henninger, Leen-Kiat Soh (CSE) Etsuko Moriyama, Ken Nickerson, Audrey Atkin (Biological Sciences) Steve Harris.
Regulatory networks 10/29/07. Definition of a module Module here has broader meanings than before. A functional module is a discrete entity whose function.
27803::Systems Biology1CBS, Department of Systems Biology Schedule for the Afternoon 13:00 – 13:30ChIP-chip lecture 13:30 – 14:30Exercise 14:30 – 14:45Break.
What is an ontology and Why should you care? Barry Smith with thanks to Jane Lomax, Gene Ontology Consortium 1.
SCB : 1 Department of Computer Science Simulation and Complexity SCB : Simulating Complex Biosystems Susan Stepney Department of Computer Science Leo Caves.
Use of Ontologies in the Life Sciences: BioPax Graciela Gonzalez, PhD (some slides adapted from presentations available at
Internet tools for genomic analysis: part 2
The bioinformatics of biological processes The challenge of temporal data Per J. Kraulis CMCM, Tartu University.
Modeling Functional Genomics Datasets CVM Lesson 1 13 June 2007Bindu Nanduri.
Introduction to molecular networks Sushmita Roy BMI/CS 576 Nov 6 th, 2014.
Computational Models in Systems Biology Karan Mangla 22 nd April, 2008.
Seminar in Bioinformatics (236818) Ron Y. Pinter Fall 2007/08.
Pathways Database System: An Integrated System For Biological Pathways L. Krishnamurthy, J. Nadeau, G. Ozsoyoglu, M. Ozsoyoglu, G. Schaeffer, M. Tasan.
Modeling Functional Genomics Datasets CVM Lessons 4&5 10 July 2007Bindu Nanduri.
Systematic Analysis of Interactome: A New Trend in Bioinformatics KOCSEA Technical Symposium 2010 Young-Rae Cho, Ph.D. Assistant Professor Department of.
Biological pathway and systems analysis An introduction.
Large-scale organization of metabolic networks Jeong et al. CS 466 Saurabh Sinha.
Ch10. Intermolecular Interactions and Biological Pathways
Genome-scale Metabolic Reconstruction and Modeling of Microbial Life Aaron Best, Biology Matthew DeJongh, Computer Science Nathan Tintle, Mathematics Hope.
Shankar Subramaniam University of California at San Diego Data to Biology.
Genetic network inference: from co-expression clustering to reverse engineering Patrik D’haeseleer,Shoudan Liang and Roland Somogyi.
Biological Pathways & Networks
GTL Facilities Computing Infrastructure for 21 st Century Systems Biology Ed Uberbacher ORNL & Mike Colvin LLNL.
ANALYZING PROTEIN NETWORK ROBUSTNESS USING GRAPH SPECTRUM Jingchun Chen The Ohio State University, Columbus, Ohio Institute.
EBI is an Outstation of the European Molecular Biology Laboratory. BioModels Database, a public model- sharing resource In silico systems biology: network.
March 24, Integrating genomic knowledge sources through an anatomy ontology Gennari JH, Silberfein A, and Wiley JC Pac Symp Biocomputing 2005:
AMATH 382: Computational Modeling of Cellular Systems Dynamic modelling of biochemical, genetic, and neural networks Introductory Lecture, Jan. 6, 2014.
Network & Systems Modeling 29 June 2009 NCSU GO Workshop.
Agent-based methods for translational cancer multilevel modelling Sylvia Nagl PhD Cancer Systems Science & Biomedical Informatics UCL Cancer Institute.
Gene Ontology TM (GO) Consortium Jennifer I Clark EMBL Outstation - European Bioinformatics Institute (EBI), Hinxton, Cambridge CB10 1SD, UK Objectives:
A Method for Protein Functional Flow Configuration and Validation Woo-Hyuk Jang 1 Suk-Hoon Jung 1 Dong-Soo Han 1
Cell Signaling Ontology Takako Takai-Igarashi and Toshihisa Takagi Human Genome Center, Institute of Medical Science, University of Tokyo.
Integrating the Bioinformatic Technology Group into your research programme Introduction People and Skills Examples Integrating the BTG Contacts BHRC Away.
A Biology Primer Part IV: Gene networks and systems biology Vasileios Hatzivassiloglou University of Texas at Dallas.
1 Departament of Bioengineering, University of California 2 Harvard Medical School Department of Genetics Metabolic Flux Balance Analysis and the in Silico.
Systems Biology ___ Toward System-level Understanding of Biological Systems Hou-Haifeng.
1 Gene function annotation. 2 Outline  Functional annotation  Controlled vocabularies  Functional annotation at TAIR  Resources and tools at TAIR.
Microarrays.
Bioinformatics MEDC601 Lecture by Brad Windle Ph# Office: Massey Cancer Center, Goodwin Labs Room 319 Web site for lecture:
Mining the Biomedical Research Literature Ken Baclawski.
A collaborative tool for sequence annotation. Contact:
An approach to carry out research and teaching in Bioinformatics in remote areas Alok Bhattacharya Centre for Computational Biology & Bioinformatics JAWAHARLAL.
Hybrid Functional Petri Net model of the Canonical Wnt Pathway Koh Yeow Nam, Geoffrey.
Genome Biology and Biotechnology The next frontier: Systems biology Prof. M. Zabeau Department of Plant Systems Biology Flanders Interuniversity Institute.
Introduction to biological molecular networks
GO based data analysis Iowa State Workshop 11 June 2009.
26/04/04 Petri nets in systems biology: creation, analysis and simulation Oliver Shaw School of Computing Science.
Tools in Bioinformatics Ontologies and pathways. Why are ontologies needed? A free text is the best way to describe what a protein does to a human reader.
Ontology Driven Data Collection for EuPathDB Jie Zheng, Omar Harb, Chris Stoeckert Center for Bioinformatics, University of Pennsylvania.
High Risk 1. Ensure productive use of GRID computing through participation of biologists to shape the development of the GRID. 2. Develop user-friendly.
High throughput biology data management and data intensive computing drivers George Michaels.
1 Survey of Biodata Analysis from a Data Mining Perspective Peter Bajcsy Jiawei Han Lei Liu Jiong Yang.
University of California at San Diego
Whole-cell models: combining genomics and dynamical modeling
Model Curation Edmund J. Crampin Auckland Bioengineering Institute
What contribution can automated reasoning make to e-Science?
University of California at San Diego
Presentation transcript:

Multiscale Modelling Project Fallot Tariq Abdulla December 2009

Outline Information Modelling – Ontologies, XML and databases Petri nets – graph based representation of networks and pathways Network Analysis – network type, motifs Integration of models

Ontologies 1.Provide a common, structured vocabulary, in order to overcome confusion in terminology. 2.Facilitate the integration and querying of heterogeneous datasets (and, increasingly, models).

Gene Ontology 1.Collaboration between model organism databases – thus inherently cross-species 2.Reference ontology – for more specific annotation, we may develop application ontologies, that reference GO and other reference ontologies 3.Split into 3 seperate ontologies: Biological Process, Cellular Component and Molecular Function

Gene Ontology: AmiGO

Rat Genome Database Nkx2.5

Rat Genome Database Jagged1

Properties Irreflexive Functional Reflexive Transitive Inverse Functional Symmetric (Horridge et al. 2009)

Properties

Automatic Classification

place transition arc inhibitory arc token Petri Nets 3 t2 t1 t3 p1 p3 p4 p2

(Gilbert, et al. 2006) v max = K cat [E]

SBML – Enzyme Reaction

KEGG Representation Is this straightforward?

(Heiner, Koch and Will 2004)

Pathways: structural differences Metabolic NetworksSignal Transduction Networks (Breitling, et al. 2008)

Phosphorylation Kinase Phosphorylated Form Phosphotase Signalling Protein

Notch Signalling (Artavanis-Tsakonas, Rand and Lake 1999)

Hybrid Petri Nets Places and Transitions can be either discrete or continuous

HFPN: Notch Signalling

XML Representation of HFPN m1m2 T1 1m1/2 P1P2 m1/2.5

How Can we understand this? Network Analysis!

Signalling Pathways are robust because: They are small world, scale free networks Power Law Distribution: P(k) ∼ k −γ

Signalling Pathways are robust because: There are redundant pathways, feedback loops, and combinatorial complex Cross-talk between pathways provide additional sites to regulate signalling

Network Motifs

(Prill, Iglesias and Levchenko 2005)

Model Checking Liveness Reachability P and T invariants

Mining Pathway Information Pathway databases are either created by curators, or through text mining of the literature Curated databases tend to be higher quality, but the breadth may be narrower

Levels of Abstraction

Why model? Generate new insights Make testable predictions Test conditions that may be difficult/impossible to study in vitro / in vivo Rule out particular explanations for an experimental observation Help identify what is right/wrong with an hypothesis

Analysis and Interpretation Validation: do the model results match experimental data? Prediction: – Sensitivity analysis – Knockout experiments

Information Management Identify building blocks / submodels Database – Models, model components – Behaviours – Properties Component reuse Version control Model checking – Maintaining temporal-logical properties

A Proposition: Find out the expression of Delta and Notch in the precursor cells of the Heart fields at an early stage Simulate to find if the patterning corresponds to what is expected

Conclusion By encoding models, literature and experimental results in XML, and storing them in web-accessible databases, intermediated by ontologies, we facilitate more holistic approaches. A range of modelling are appropriate to different levels of scale In the places where these can begin to be integrated, there is insight to be gained in silico

References Horridge, Matthew, Simon Jupp, Georgina Moulton, Alan Rector, Robert Stevens, and Chris Wroe. "A Practical Guide To Building OWL Ontologies Using Protégé 4." CO-ODE. October 16, Gilbert, David, et al. "Computational methodologies for modelling, analysis and simulation of signalling networks." Breifings in Bioinformatics 7, no. 4 (2006): Heiner, Monika, Ina Koch, and Jürgen Will. "Model validation of biological pathways using Petri nets— demonstrated for apoptosis." Biosystems 75 (2004): Breitling, Rainer, David Gilbert, Monika Heiner, and Richard Orton. "A structured approach for the engineering of biochemical network models, illustrated for signaling pathways." Briefings in Bioinformatics 9, no. 5 (2008): Matsuno, Hiroshi, Ryutaro Murakami, Rie Yamane, Naoyuki Yamasaki, Sachie Fujita, and Haruka Yoshimori. "Boundary Formation by Notch Signalling in Drosophila Multicellular Systems: Experimental Observations and Gene Network Modeling by Genomic Object Net." Pacific Symposium on Biocomputing. Kauai, Hawaii: World Scientific, Artavanis-Tsakonas, Spyros, Matthew D. Rand, and Robert J. Lake. "Notch Signaling: Cell Fate Control and Signal Integration in Development." Science 284 (1999): Prill, Rober J., Pablo A. Iglesias, and Andre Levchenko. "Dynamic Properties of Network Motifs Contribute to Biological Network Organization." PLOS Biology 3, no. 11 (2005):

Further Reading Fisher, Steven A., Lowell B. Langille, and Deepak Srivastava. "Apoptosis During Cardiovascular Development." Circulation Research, 2000: Gittenberger-de Groot, A. C., and R. E. Poelmann. "A Subpopulation of Apoptosis-Prone Cardiac Neural Crest Cells Targets to the Venous Pole: Multiple Functions in Heart Development?" Developmental Biology, 1999: Barabási, Albert-László, and Zoltán N. Oltvai. "Network Biology: Understanding the Cell’s Functional Organization." Nature Reviews: Genetics, 2004: Rector, Alan, Jeremy Rogers, and Thomas Bittner. "Granularity scale and collectivity: when size does and does not matter." Journal of Biomedical Informatics, no. 39 (2006): Fisher, Jasmin, and Thomas A Henzinger. "Executable cell biology." NATURE BIOTECHNOLOGY 25, no. 11 (2007): Novere, Nicholas Le, Melanie Courtot, and Camille Laibe. "Adding Semantics in Kinetics Models of Biochemical Pathways." 2nd International ESCEC Symposium on Experimental Standard Conditions on Enzyme Characterizations. Rhein: Beilstein Institut, Niessen, Kyle, and Aly Karsan. "Notch Signalling in Cardiac Development." Circulation Research, 2008: Walker D C, Southgate J S, Hill G, Holcombe M, Hose D R, Wood S M, MacNeil S and Smallwood R H (2004) The Epitheliome: modelling the social behaviour of cells. BioSystems 76:89-100