BiNoM Tutorial

Andrei Zinovyev, Laurence CalzoneUMR U900 INSERM/Institut Curie/Ecole des Mines de Paris

Wednesday, April 30th

BiNoM is a plugin for Cytoscape

http://cytoscape.org/

Install and Start Cytoscape+BiNoM

1) Download Cytoscape installer version 2.4.0 from http://cytoscape.org

2) Download BiNoM from http://bioinfo-out.curie.fr/projects/binom/BiNoM_all.jar

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 2.6.0. These technical issues will be resolved very soon.

Starting course about Cytoscape

Short introduction into Cytoscape

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 menuPlugins / BiNoM Analysis / Prune graph

Initial network Result of operation

Choose in the menuPlugins / BiNoM Analysis / Monomolecular reactions to edges

Initial network Result of operation

Choose in the menu Plugins / BiNoM Analysis / Exclude intermediate nodes

Initial network Result of operation

Choose in the menu Plugins / BiNoM Analysis / Material components

NFkB

IkBInitial network

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

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

Section 2. BiNoM and BioPAX

Biological PAthway eXchange format

BioPAX

Molecular InteractionsPro:Pro All:All

PSI

Biochemical Reactions

SBML,CellML

Regulatory PathwaysLow Detail High Detail

GeneticInteractions

Interaction NetworksMolecular Non-molecularPro:Pro TF:Gene Genetic

Metabolic PathwaysLow Detail High Detail

DatabaseExchange Formats

Simulation ModelExchange Formats

SmallMolecules (CML)

RateFormulas

BioPAXis formulated on Web Ontology

Language (OWL)

BioPAX level 2.0

Importing BioPAX files

Open example fileat 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 viewReimport the MAPK_Reactome example

with new pathway hierarchy options

Get BioPAX annotationPlugins / BiNoM BioPAX Utils/BioPAX Property Editor

Select someNodes first

Get BioPAX annotationBiNoM BioPAX Utils/BioPAX Property Editor

Browse by clicking at the color labels

Get Complete BioPAX annotationPlugins / 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_Reactome5. 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

BiNoMBig

BioPAXfile

To work with big BioPAX file, BiNoM user should generate BioPAX index

Reactome.owl file

ReactomeIndex

.xgmml fileBiNoM BiNoMQuery

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 proteinsby 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 involvedPlugins / BiNoM BioPAX Query / Standard query

Extract all selected reaction annotationsPlugins / 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 anotherPlugins / BiNoM BioPAX Query / Index Path Analysis

Finding the shortest path and suboptimal path from one protein to anotherPlugins / BiNoM BioPAX Query / Index Path Analysis

1) Select nodes2) 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”