network components and biological network construction methods
TRANSCRIPT
August 15th, 2013
Vijayaraj Nagarajan PhD Computational Biologist BCBB/OCICIB/NIAID, National Institutes of Health
Outline
§ Network Components – Basic components of a network – Basic features of a network – Types of biological networks
§ Biological Network Construc9on Methods – Methods (Logic and concept)
– Genome Sequences – “omics” data – Literature mining – Integra9on – Meta-‐networks
§ Nodes § DNA/RNA/Protein/Metabolite/Ontology
§ Edges Directed § Dis9nc9on between source and target
• Ac9va9on (direct/indirect) • Repression (direct/indirect)
Undirected § No dis9nc9on between source and target
• Co-‐expression (indirect) • Binding (direct) • Similarity/strength
Basic Components
Basic Features
§ Degree – Number of connec9ons that a node has
§ Distance – Number of connec9ons between two nodes, in a shortest path
§ Path – A sequence of connec9ons – Is there a path (reachability) – Mean Shortest Path distance (closeness) – In how many shortest paths (betweenness)
§ Size of a network (Number of nodes) § Density of a network (Propor9on of the connec9ons) § Mo9fs/Cliques/Clusters/Sub-‐networks
Loops
Chains
Parallels
Multi-input Single input
Basic Features
Types of Biological Networks § DNA-‐Protein
• Transcrip9onal regulatory networks • Methyla9on networks
§ RNA-‐RNA • miRNA regulatory networks
§ RNA-‐Protein • Splicing regulatory networks
§ Protein-‐Protein • Co-‐expression networks • Co-‐localiza9on networks • Co-‐evolu9on networks • Structure networks • Pathway networks • Protease regulatory networks • Signal transduc9on networks • Gene Ontology networks
meta-networks
Single gene
§ Regulators/Co-‐regulators § Upstream/Downstream elements in the network § Global connec9vity/interconnec9vity § Func9onal features § Differen9ally expressed subnetworks § One gene – one disease : bunch of genes – pathways § Nextgen sequencing data § Meta-‐analysis
List of genes
Why Build/Analyze Biological Networks ?
Outline
§ Network Components – Basic components of a network – Basic features of a network – Types of biological networks
§ Biological Network Construc9on Methods – Methods (Logic and concept)
– Genome Sequences – “omics” data – Literature mining – Integra9on – Meta-‐networks
How to Build Biological Networks ?
§ Search/Retrieve from knowledge bases § Predict from genome sequences § Predict from “omics” data § Predict from literature § Integrate and analyze § Meta-‐networks from genome/phenome scale data analysis
Protein Engineering, Vol. 14, No. 9, 609-614, September 2001
PredicCon from genome sequences
§ Gene neighbor (gene cluster, gene order) § Gene fusion (RoseWa stone) § Phylogene9c profiling § Co-‐evolu9on § Mirror tree
PredicCon from “omics” data
§ Co-‐expression (Correla9on, Mutual Informa9on)
PPI PredicCon Using Microarray Data
§ Co-‐expression concept – Correla9on Coefficient
• SIMoNE (Sta9s9cal Inference for Modular Networks) -‐ R – Mutual Informa9on
• Reference Networks • ARACNE (Algorithm for Reconstruc9on of Accurate Cellular Networks) – R, geWorkbench
• CLR (Context Likelihood of Relatedness) – R • MRNET (Maximum Relevance/Minimum Redundancy) – R • MONET (Modularized NETwork Learning) -‐ Cytoscape
– Bayesian Network
Meta-networks
13 http://www.pnas.org/content/105/29/9880
Predicted PPI Network
§ Could form a complex § Could be func9onally associated § Could be involved in a same metabolic pathway § Could be involved in a specific signal transduc9on path § False posi9ve
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