From Functional Genomics to Physiological Model: the Gene ...

From Functional Genomics to Physiological Model: the Gene ...

Pathways analysis Iowa State Workshop 11 June 2009 All tools and materials from this workshop are available online at the AgBase database Educational Resources link. For continuing support and assistance please contact: [email protected] This workshop is supported by USDA CSREES grant number MISV-329140. Pathways analysis enables Analysis of data in the context of molecular mechanisms to move beyond statistical analysis of expression to novel biological insights

Applying biological filters to focus in on the changes most relevant to experimental model Comparison of affected pathways and phenotypes across platform, time, dose etc (www.ingenuity.com) What regulatory relationships exist between the genes, proteins in my dataset? Networks Which biological and disease processes are most relevant to my

genes of interest? Functional analysis Which well-characterized cell signaling and metabolic pathways are most relevant to my experimental data? Metabolic And Signaling pathways http://www.ingenuity.com Cytoscape

Cytoscape is a freely-available (open-source, java-based) bioinformatics software platform for visualizing biological networks (e.g. molecular interaction networks) and analyzing networks with gene expression profiles and other data Core Features Customize network data display using visual styles Powerful graph layout tools

Easily organize multiple networks Easily navigate large networks Filter the network Plugin API Cytoscape includes a flexible plugin architecture that enables developers to add extra functionality beyond that provided in the core

Some plugins jActiveModules: identify significant active subnetworks Expression Correlation Network: cluster expression data Agilent Literature Search: build networks by extracting interactions from scientific literature. MCODE: finds clusters of highly interconnected regions in networks cPath: query, retrieve and visualize interactions from the MSKCC Cancer Pathway database BiNGO: determine which Gene Ontology (GO) categories are statistically over-represented in a set of genes

Motif Finder: runs a Gibbs sampling motif detector on sequences for nodes in a Cytoscape network. Exhaustive list at http://chianti.ucsd.edu/cyto_web/plugins/index.php Gene Ontology enrichment analysis BiNGO plugin Gene Ontology structure Analysis tools (commercial) Ingenuity Pathway Analysis http://www.ingenuity.com Networks Pathways Functions and diseases Gene Ontology (GO) groups

Pathway studio http://www.ariadnegenomics.com/ GSEA Pathways IPA analysis included as IPA.txt Data curation Ingenuity : Manually curated database by Ph.D level scientists (mining 32 different peer reviewed journals). Pathway studio : Automated curation by Medscan Reader using Natural language processing (NLP)

technology. Mining Pubmed abstracts and peer reviewed journals (users can do their own text mining) Comparison Criteria Features Proportion of proteins involved in modeling Data generation Display Test Dataset: 3,600 bovine spermatozoa proteins (Comparison by Divya Swetha Peddinti) Feature Ingenuity Pathway analysis (IPA)

Pathway studio Input GI number Microarray ID Affymetrix ID GenBank Swiss Prot Accession Unigene ID Name orAlias HUGO ID Entrez gene GenBank Microarray ID Swiss Prot Accession Unigene ID Name or Alias HUGO ID

Databases Contains biological interactions data for human, mouse, rat Orthologous mapping available for dog, Cow, Chimp, Chicken, Rhesus macaque monkey, Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Danio rerio Contains biological data for human, mouse, rat, bacteria, chicken, Zebra fish, frog, cow, bee, dog, Arabidopsis, Drosophila, Yeast, and transplantation research etc..

Ingenuity Pathway analysis (IPA) Pathway studio Statistical test The significance value( p value) assigned to the function / pathways using Fischers exact test The statistical significance of the overlap between the protein list and a GO group or pathway using the Fischers

exact test. Updates Quarterly Quarterly Networks Builds networks with a maximum of 35 genes/ proteins - Proteins involved in modeling 120 100 80

0.15 42.5 60 99.85 40 20 57.5 Proteins not involved in modeling Proteins involved in modeling 0 Pathwaystudio

Ingenuity Data generation 50 44 40 33 Ingenuity pathway anlaysis 30 20 Pathway studio

10 0 Pathways 37 7 26 Pathway display EGF signaling pathway Equally efficient at drawing networks of relationships.

IPA : simplifies the pathway display and creates more manageable user friendly network for users to analyze. Pathway Studio: Shows the relations in a table format. Ariadne supported database statistics Mamamlian ResNet 1.5 Million molecular interactions and functional relationships from the entire PubMed (17,000,000 abstracts) and 61 full text journals for 110,435 proteins

13,533 small molecules 2814 cellular processes 2,410 diseases Pathways: 227 Receptor signaling pathways 21 new cellular process regulation pathways Atlas of Signaling - all cellular signaling on one map

Plant ResNet Relations to Arabidopsis proteins, (and rice genes that are mapped to Arabidopsis), Protein annotation for eight other plant species; Over 90,000 functional relationships and molecular interactions from 117,000 plant-specific abstracts and 8 plant-specific full-text journals for 71,501 proteins 3,831 small molecules 915 cellular processes 97 plant diseases Pathways: 17 Plant Signaling Pathways 315 AraCyc pathways

Journals: Annals of Botany Crop Science Journal of Experimental Botany New Phytologist Plant Cell Plant, Cell and Environment Plant Journal Plant Physiology

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