Transcript Pathways, Networks and Systems Session Introduction Vincent Schächter Alfonso Valencia ISMB’05 – Detroit, MI.

Pathways, Networks and Systems Session
Introduction
Vincent Schächter
Alfonso Valencia
ISMB’05 – Detroit, MI
Biological networks and systems : context
• (Partial) catalog of functional elements available : genes,
proteins, RNAs
• High-throughput measurement technologies
– Elements of mechanisms : protein-protein interactions, proteinDNA interactions, biochemical reactions…
– Information on cellular states : mRNA expression, protein
expression, phenotype, microscopy & imaging, metabolite
concentrations, metabolite fluxes…
• Increasing realization of the limits of functional
understanding at the level of individual genes / proteins
ISMB’05 – Detroit, MI
Motivations for the study of biological
networks and systems
• Help structure, represent and interpret experimental data on
interactions and states
– Integrate different types of experimental data
– Relate mechanisms to states
• Build a detailed understanding of cellular processes
– allowing prediction of cellular state observables at different levels of
detail
– allowing intervention with predictable & measurable outcomes
• Guide experiments by providing testable hypotheses obeying
parsimony criteria
• Compare processes within and across organisms, gain insight into
their evolution
• Better characterize the function of single genes
ISMB’05 – Detroit, MI
Types of biomolecular networks
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Gene regulatory networks
Vertices : genes
Edges : regulatory influences
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Metabolic networks
Vertices : metabolites, reactions (catalyzed
by enzymes)
Edges : consumption, production
Degenerate networks : enzymes,
metabolites
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Protein-protein interaction networks
Vertices : proteins
Edges : physical interactions
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Signaling networks
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ChIP-Chip
Gene expression data
Sequence
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Sequence
Classical biochemistry
Mass spectrometry
Isotope labeling
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Yeast two-hybrid
Mass spectrometry
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Measurements of post-translational
modifications
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Sequence (of several organisms)
Expression data
Any data type allowing definition of a
similarity measure…
Vertices : proteins with state information
Edges : interactions modifying states
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Networks of functional links
Vertices : genes
Edges : functional relationships
ISMB’05 – Detroit, MI
Computational Biology of Networks
• Modeling
• Reconstruction
• Simulation
• Analysis
– Structural (topological) properties
– Dynamical properties
• Tools for visualization and navigation
ISMB’05 – Detroit, MI
Pathways & Networks @ISMB’05
• Pathways, networks and systems session
– 8 papers selected from 64 submissions
• Pathways, networks and proteomics session
– Oral abstracts, Sunday morning and Wednesday
• BioPathways SIG
– Started at ISMB 2000, yearly meeting
– Sessions on :
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metabolic networks
regulatory networks
protein-protein interaction networks
database, exchange formats & software tools
ISMB’05 – Detroit, MI
Modeling
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Design modeling frameworks adapted to
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the type of biological network / system
the type(s) of experimental data available to build the model
the type of predictions the model will be used for
the type of experimental data model predictions will be compared to
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Design predictive methods to answer specific questions on network
architecture or dynamics
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Model, validate, refine specific biological systems
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Validation of Qualitative Models of Genetic Regulatory Networks by Model Checking:
Analysis of the Nutritional Stress Response in Escherichia coli
Batt, Ropers, de Jong, Geiselmann, Mateescu, Page, Schneider
Sun, 2:50-3:15pm
Modeling the Organization of the WUSCHEL Expression Domain in the Shoot Apical
Meristem
Jönsson, Heisler, Reddy, Agrawal, Gor, Shapiro, Mjolsness, Meyerowitz
Sun, 4:35-5pm
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ISMB’05 – Detroit, MI
Network Reconstruction
Infer networks from experimental data
– using one or several experimental data types
– using prior knowledge about network structure
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Challenges :
– Data quantity and availability
– Validation sets ?
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Methods
– Machine learning
– Comparison across organisms, evolutionary reasoning
Protein-protein interaction prediction
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Kernel Methods for Predicting Protein-protein Interactions
Ben-Hur, Noble
Sun, 3:45-4:10pm
Predicting Protein-Protein Interaction by Searching Evolutionary Tree Automorphism Space
Jothi, Kann, Przytycka
Tue, 2:10-2:35pm
Metabolic Pathways Reconstruction
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Supervised Enzyme Network Inference from the Integration of Genomic Data and Chemical Information
Yamanishi, Vert, Kanehisa
Tue, 3:05-3:30pm
Automatic Detection of Subsystem/Pathway Variants in Genome Analysis
Ye, Osterman, Overbeek, Godzik
Sun, 4:10-4:35pm
ISMB’05 – Detroit, MI
Analyses of network structure
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Motivation
– Experimental data on the mechanistic details of network dynamics not available
at large scale
– Identifying biologically relevant dynamical properties of large networks is a hard
problem
 Focus first on topological properties of networks
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Goals
– Build simplified, tractable view of network architecture : modules…
– Identify properties of network structure with potential interpretation as traces of
underlying biological mechanisms
• Dynamics : how structure reflects dynamics
• Evolution : how structure reflects evolutionary history and thus fitness constraints
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Automatic Detection of Subsystem/Pathway Variants in Genome Analysis
Ye, Osterman, Overbeek, Godzik
Sun, 4:10-4:35pm
Mining Coherent Dense Subgraphs Across Massive Biological Networks for
Functional Discovery
Hu, Yan, Huang, Han, Zhou
Tue, 3:55-4:20pm
ISMB’05 – Detroit, MI
Function prediction using networks
Predict function of individual genes/proteins using network structure
Variations on the intuitive guilt-by-association idea
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Whole-proteome Prediction of Protein Function via Graph-theoretic Analysis of
Interaction Maps
Nabieva, Jim, Agarwal, Chazelle, Singh
Tue, 3:30-3:55pm
ISMB’05 – Detroit, MI
Pathways, Networks and Systems Session
Sunday afternoon :
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Validation of Qualitative Models of Genetic Regulatory Networks by Model Checking:
Analysis of the Nutritional Stress Response in Escherichia coli
Batt, Ropers, de Jong, Geiselmann, Mateescu, Page, Schneider
Sun, 2:50-3:15pm
Kernel Methods for Predicting Protein-protein Interactions
Ben-Hur, Noble
Sun, 3:45-4:10pm
Automatic Detection of Subsystem/Pathway Variants in Genome Analysis
Ye, Osterman, Overbeek, Godzik
Sun, 4:10-4:35pm
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Modeling the Organization of the WUSCHEL Expression Domain in the Shoot Apical
Meristem
Jönsson, Heisler, Reddy, Agrawal, Gor, Shapiro, Mjolsness, Meyerowitz
Sun, 4:35-5pm
ISMB’05 – Detroit, MI
ISMB’05 – Detroit, MI