SYSTEM BIOLOGY AND ITS TOOLS

BY GAURAV DIWAKAR

44820

Systems Biology Definition:

• A field that seeks to the study of relationships and interactions between various parts of a biological system (metabolic pathways, organelles, cells and organisms) and to integrate this information to understand how biological systems function.

• Systems biology is a relatively new biological study field that focuses on the systematic study of complex interactions in biological systems.

What is a biological network?

• Researchers are learning that biological pathways are far more complicated than once thought. Most pathways do not start at point A and end at point B. In fact, many pathways have no real boundaries, and they often work together to accomplish tasks. When multiple biological pathways interact with each other, it is called a biological network.

Biology NetworksA network is a set of nodes and a set of directed or undirected

edgesbetween the nodes.Transcriptional Regulatory Network:• Gene are the nodes and edges are directed

Signal transduction network:• Proteins are nodes and edges are directed

Metabolite network:• Metabolite are nodes and edges are directed

Parameter of Biological network

• Degree: the degree of a node in a network is the number of connections it has to other nodes

• Diameter: largest distance between any two nodes in the network

• Average path length: Average distance between any two nodesin the network

• Betweenness centrality: It is an indicator of a node's centrality in a network. It is equal to the number of shortest paths from all vertices to all others that pass through that node.

• Clustering coefficient: A measure of the degree to node which tend to cluster together

Database resources for System Biology

• Microarray gene expression database• ArrayExpress (http://www.ebi.ac.uk/microarray-as/ae/)

• GEO (http://www.ncbi.nlm.nih.gov/geo/)

• CIBEX ( http://cibex.nig.ac.jp/index.jsp)

• Protein-protein interaction database• BINDplus (Biomolecular Object Network Database)

http://www.thomsonreuters.com/products_services/scientific/BINDplus

• DIP(The Database of Interacting Proteins) http://dip.doe-mbi.ucla.edu/dip/Main.cgi

• MINT(The Molecular INTeraction database) http://mint.bio.uniroma2.it/mint/Welcome.do

• STRING(Search Tool for the Retrieval of Interacting Genes/Proteins) http://string.embl.de/

• Pathway database• KEGG(Kyoto Encyclopedia of Genes and Genomes)

http://www.genome.jp/kegg/

• REACTOME() http://www.reactome.org/

• MetaCyc http://metacyc.org/

• EcoCyc http://ecocyc.org/

• KEGG: Kyoto Encyclopedia of Genes and Genomes: KEGG

(Kyoto Encyclopedia of Genes and Genomes) is a bioinformatics resource for linking genomes to life and the environment.

• EcoCyc: Encyclopedia of Escherichia coli K-12 Genes and Metabolism: EcoCyc is a scientific database for the bacterium Escherichia coli K-12 MG1655. The EcoCyc project performs literature-based curation of the entire genome, and of transcriptional regulation, transporters, and metabolic pathways.

• BioModels Database: BioModels Database is a data resource that allows biologists to store, search and retrieve published mathematical models of biological interests.

• BiGG Database: The BiGG database is a metabolic reconstruction of human metabolism designed for systems biology simulation and metabolic flux balance modeling. It is a comprehensive literature-based genome-scale metabolic reconstruction that accounts for the functions of 1,496 ORFs, 2,004 proteins, 2,766 metabolites, and 3,311 metabolic and transport reactions. It was assembled from build 35 of the human genome. Need an username and password.

Network Visualization Tools • Cytoscape ( http://www.cytoscape.org/)

• BioTapestry (http://www.biotapestry.org/)

• BioUML ( http://www.biouml.org/)

• CADLIVE ( http://www.cadlive.jp/)

• Edinburgh Pathway Editor (http://www.bioinformatics.ed.ac.uk/epe/)

Modeling &Simulation tools

• CellDesigner http://www.celldesigner.org/

• Jarnac/JDesigner http://sbw.kgi.edu/

• COPASI http://www.copasi.org/

• E-Cell http://www.e-cell.org/

Cell Desginer

• CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. Networks are drawn based on the process diagram, with graphical notation system proposed by Kitano, and are stored using the Systems Biology Markup Language (SBML).

Cytoscape

• Cytoscape is an open source bioinformatics software platform for visualizing molecular interaction networks and integrating these interactions with gene expression profiles and other state data.

Layouts

• 12 algorithms available through plugins• Zooming, hide/show, alignment

yFiles Organic

yFiles Circular

Network Parameters

Graph Analysis

Protein-Protein Interaction Database

• STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) is a biological database and web resource of known and predicted protein-protein interactions.

• The STRING database contains information from numerous sources including:Experimental data Public text collections.

• It is freely accessible and it is regularly updated. • The latest version 10.0 contains information on about 5.2

millions proteins from 1133 species.

Step 1

Step 2

Step 3

Step 4

Network parameter

SWISS MODEL

• SWISS-MODEL is a fully automated protein structure homology-modelling server, accessible via the ExPASy web server, or from the program DeepView (Swiss Pdb-Viewer). The purpose of this server is to make Protein Modelling accessible to all biochemists and molecular biologists worldwide.

• https://swissmodel.expasy.org

APPLICATION OF SYSTEM BIOLOGY

• System biology in Crop improvement• System biology in drug discovery• Network biology• Topological analysis of Biological network

THANK YOU