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Tools and Algorithms in Bioinformatics GCBA815, Fall 2015 Week-10: IPA: Ingenuity Pathway Analysis Babu Guda Department of Genetics, Cell Biology and Anatomy University of Nebraska Medical Center __________________________________________________________________________________________________ 11/6/2015 GCBA 815 Ingenuity Pathway Analysis (IPA) http://www.ingenuity.com • A leading commercial software for biological pathway and network analysis • Ingenuity knowledge Base (expert curated information from the literature) • Public databases (Entrez Gene, RefSeq, OMIM, GWAS, GO, HMDB, GNF, KEGG, IntAct, BIND, Clinical trials, DrugBank, etc.) • Four major products • IPA (UNMC has two concurrent licenses) • iReport: Interactive web-based report • Variant Analysis: To identify variants from sequencing data • BioProfiler: Profiles a disease or phenotype by associating genes and compounds __________________________________________________________________________________________________ 11/6/2015 GCBA 815 1 __________________________________________________________________________________________________ 11/6/2015 GCBA 815 Different types of analyses • Browsing the database (genes, molecules, diseases, pathways and functions using the IPA knowledgebase) • Gene expression analysis • Pathway analysis (signaling, metabolic, disease) • Interaction network analysis • Grow/build networks from seed molecules • Trim larger networks • Upstream regulator analysis • Mechanistic network analysis • Human Isoform view • Molecule activity predictor (MAP) • Predicted cascading effects of altering one molecule in a pathway • Hypothesis generation __________________________________________________________________________________________________ 11/6/2015 GCBA 815 2 Some special features of IPA • Search feature against the entire IPA Knowledgebase • Molecule pages sorted by species (human/mouse) • Directly access PubMed records for each annotation • Share your analysis results with other IPA registered users • Can also share only part of the result • Import external pathways into IPA (in SBML format) • Use Path Designer to edit pathway/network diagrams • MicroRNA target filter • Biomarker analysis • Export data and images for reports/publications __________________________________________________________________________________________________ 11/6/2015 GCBA 815 Upload the data • Data in a structured format (excel, tab-delimited, etc.) • Limit the header to only the first row • Keep the ‘flexible format’ option (default) • Identifier type: Automatic, but change if inappropriate • Select only the columns that you want to upload and ignore the rest • Select appropriate units like fold change, z-score, p-value, etc. • Prompts you to create a new project; all your analysis results will be stored in this project folder, which can be accessed from the left panel • General default setting are good unless you want to customize • Step-wise directions are available at • http://ingenuity.force.com/ipa/IPATutorials?id=kA150000000TPy1# __________________________________________________________________________________________________ 11/6/2015 GCBA 815 3 Running Core Analysis • Mapped Ids: Identified by the IPA database • Unmapped Ids: Unidentified by the IPA database • Analysis –ready molecules: Identified and also contain information in the database • Run the analysis for individual observations • If more than one observation is selected, analysis is run independently for each and saved under separate names __________________________________________________________________________________________________ 11/6/2015 GCBA 815 Network/Pathway Analysis • Grow: Connected molecules for a selected molecule can be grown based on the known connections in the literature • Trim: Connections can be removed from a larger network based on certain criteria • Connect: Two sets of unconnected genes can be connected via the shortest path • Pathway Explorer: Above tools can be used to explore pathways • Pathway Designer: Offers graphical representation of molecules for generating publication quality figures • Canonical pathways can be selected and genes from the dataset can be overlaid __________________________________________________________________________________________________ 11/6/2015 GCBA 815 4