BiNoM Tutorial Andrei Zinovyev, Laurence Calzone UMR U900 INSERM/Institut Curie/Ecole des Mines de Paris Wednesday, April 30th

BiNoM is a plugin for Cytoscape

Install and Start Cytoscape+BiNoM 1) Download Cytoscape installer version from 2) Download BiNoM from 3) Copy BiNoM_all.jar into the ‘plugins’ folder of Cytoscape 4) Remove (better, backup) xercesImpl.jar from the ‘lib’ folder of Cytoscape Attention : BiNoM is not yet compatible with the latest version of Cytoscape These technical issues will be resolved very soon.

Starting course about Cytoscape

Short introduction into Cytoscape

Main concept : directed graph with attributes source target Attribute1Name : Value Attribute2Name : Value AttributeYName : Value AttributeXName : Value

Short introduction into Cytoscape Selected nodes

Short introduction into Cytoscape

BiNoM – Biological Network Manager

Naming convension

Section 1. Basic Network Analysis tools in BiNoM

Importing CellDesigner (SBML) files Open NFKB_final.xml example

Importing CellDesigner (SBML) files Reaction network

Choose in the menu Plugins / BiNoM Analysis / Prune graph Initial network Result of operation

Choose in the menu Plugins / BiNoM Analysis / Monomolecular reactions to edges Initial network Result of operation

Choose in the menu Plugins / BiNoM Analysis / Exclude intermediate nodes Initial networkResult of operation

Choose in the menu Plugins / BiNoM Analysis / Material components NFkB IkB Initial network

BiNoM Analysis / Get cycle decomposition Apply from the initial network

1. Select and IkB_alpha:NFkB nodes (holding Shift key) 2. Choose in the menu: Plugins / BiNoM Analysis / Path analysis

BiNoM I/O: Export current network to CellDesigner 1.Select some nodes 2.File->New->Network->From selected nodes, all edges 3.BiNoM I/O->Export current network to CellDesigner 4.Associate the network with NFKB_final.xml 5.Save to a new xml file 6.Open the newly created file in CellDesigner

Section 2. BiNoM and BioPAX

Biological PAthway eXchange format BioPAX Molecular Interactions Pro:Pro All:All PSI Biochemical Reactions SBML, CellML Regulatory Pathways Low Detail High Detail Genetic Interactions Interaction Networks Molecular Non-molecular Pro:Pro TF:Gene Genetic Metabolic Pathways Low Detail High Detail Database Exchange Formats Simulation Model Exchange Formats Small Molecules (CML) Rate Formulas

BioPAX is formulated on Web Ontology Language (OWL) BioPAX level 2.0

Importing BioPAX files Open example file at Desktop/ Pathway Charting/ MAPK_Reactome.owl

Reaction network (RN) Apply Layout -> yFiles -> Organic layout

Pathway hierachy (PS) Apply Layout -> yFiles -> Hierarchic layout

Protein-protein interactions (PP) Apply Layout -> yFiles -> Organic layout

Example of combined view Apply Plugins->Merge networks

Alternative Pathway view Reimport the MAPK_Reactome example with new pathway hierarchy options

Get BioPAX annotation Plugins / BiNoM BioPAX Utils/BioPAX Property Editor Select some Nodes first

Get BioPAX annotation BiNoM BioPAX Utils/BioPAX Property Editor Browse by clicking at the color labels

Get Complete BioPAX annotation Plugins / BiNoM BioPAX Utils / BioPAX Class tree…

Exporting subnetwork: 1.Select subtree 2.File->New->Network->From selected nodes, all edges

Exporting subnetwork: 3. Plugins->BiNoM->Export current network to BioPAX 4. Associate with MAPK_Reactome 5. Save to ERK2.owl

Exporting subnetwork: 6. Reopen ERK2.owl using Plugin->BiNoM I/O-> Import BioPAX

Section 3. Using BiNoM with pathway databases

Pathway Database -> BioPAX -> BiNoM query Cancer Cell Map Reactome BioBase INOH HumanCyc Nature/NCI Pathway Interaction KEGG BiNoM Big BioPAX file

To work with big BioPAX file, BiNoM user should generate BioPAX index Reactome.owl file Reactome Index.xgmml file BiNoM Query Network

Preparing database: Plugins / BiNoM BioPAX Query / Generate Index

Loading index: Plugins / BiNoM BioPAX Query / Load Index The accession number file (list of synonyms) is optional. It facilitates identifying proteins by name or other Ids

Plugins / BiNoM BioPAX Query -> Select entities IGF_1 IGFBP_3 pRB

Plugins / BiNoM BioPAX Query / Standard query

Get all reactions in which IGF_1 is involved Plugins / BiNoM BioPAX Query / Standard query

Extract all selected reaction annotations Plugins / BiNoM BioPAX Query / Standard query

Plugins / BiNoM Analysis / Extract Reaction Network Plugins / BiNoM Analysis / Mono-molecular Reactions To Edges Simplifying the query result view

Finding the shortest path from one protein to another Plugins / BiNoM BioPAX Query / Index Path Analysis

Finding the shortest path and suboptimal path from one protein to another Plugins / BiNoM BioPAX Query / Index Path Analysis 1) Select nodes 2) Open dialog, change parameters 3) Apply hierarchic layout

Q: Why are there some hanging nodes in the tree? A: Because there are connections “through complexes”