Ingenuity Pathways Analysis (IPA)

Capabilities

Search and Explore Biological and Chemical Knowledge

IPA's Search & Explore capabilities offer researchers access to the most current Findings available on genes, drugs, chemicals, protein families, normal cellular and disease processes, and signaling and metabolic pathways. Use IPA's extensive repository of biological and chemical knowledge to get up to speed in a new area of research, or generate targeted search results and then act on those results to build interactive graphical representations of in vivo or in vitro experimental systems.

Search
Use Search to look for information on genes and chemicals, their impact on diseases and cellular processes, and their role in pathways.

• Build interactive pathways representing the key genes, chemicals, and processes in experimental systems of interest
• Validate experimental assumptions
• Generate testable hypotheses by using molecule or relationship filters to leverage only the Findings related to your experimental model
• Understand the biological effects of chemicals

Search for genes, proteins, metabolites, or chemicals that are:

• Clinical Biomarkers
• Localized to a specific cell compartment
• Targeted by FDA approved drugs or clinical candidates
• Involved in a particular disease or process
• Members of a specific protein or chemical family
• Most relevant by running combinations of searches to rapidly generate lists of genes with biological characteristics

ChemView
ChemView provides access to chemical content describing therapeutic information, target protein, toxicity, bioavailability, LD50, PK/PD, metabolism, CAS number, synonyms (including systematic name and brand names for drugs), chemical formula, and SMILES notation.

• Find novel intervention points in pathways by identifying chemical reagents or compounds that affect the activity of key players in pathways, networks, and cellular processes.
• Utilize chemical content to build pathways and working models representing compound mechanism of toxicity and mechanism of action.
• Include chemicals when generating networks and analyzing datasets.
• Add chemicals to custom pathways.
• Access drug and chemical information such as drug manufacturer, clinical trial, and link to NCT website for each trial displayed.

Dynamic Signaling & Metabolic Pathways
Use Ingenuity's extensive library of well-characterized signaling and metabolic pathways as a starting point for exploration and a bridge between novel discovery and known biology. Layer in novel insights, custom SBML pathways imported into IPA, drugs, and 'omics data.

• Explore beyond the boundaries of well-characterized signaling and metabolic pathways to incorporate the molecular relationships that are the most relevant to the experimental system being studied.
• Customize pathways using IPA's extensive molecular interaction content.
• Understand chemical effects on genes; find upstream activators, and downstream transcriptional targets of pathways.
• Find predicted and demonstrated mRNA targets of microRNA.
• Drill down to the Findings curated from the scientific literature.
• Layer in expression, proteomic, and copy number data.
• Browse pathway libraries by function to quickly identify pathways most relevant to your biological question.
• Utilize descriptive pathway summaries to quickly clarify a pathway’s relevance and identify key biological processes that are downstream of a pathway.
• Generate Pathway Reports that provide a broader understanding of the biological and therapeutic relevance of a pathway.

My Pathways & Lists
Build custom libraries of pathways representing disease mechanisms, drug mechanism of action and mechanism of toxicity. Create custom, literature-supported signaling pathways with proteins of interest. Store collections of custom pathways and lists for subsequent core, IPA-Tox™, IPA-Biomarker™, or IPA-Metabolomics™ analyses.

• Use the Build tools to edit and expand networks based on the molecular relationships most relevant to the project:
  • Transcriptional networks
  • Phosphorylation cascades
  • Protein-Protein or Protein-DNA interaction networks
  • microRNA-mRNA target networks
  • Chemical effects on proteins
• Use Search results as building blocks for custom pathways
  • Identify cross-talk between biological processes and pathways
  • Understand whether gene lists and signatures are tightly connected at the molecular level

Path Explorer
Find relevant regulatory paths and physical interactions between genes of interest.

• Find biological paths that connect one set of genes to another.
• Identify regulatory events that lead from signaling events to transcriptional effects.
• Understand toxicity responses by exploring connections between drugs or targets and related genes or chemicals.

Analyze and Interpret Data

IPA Core Analysis
IPA delivers a rapid assessment of the signaling and metabolic pathways, molecular networks, and biological processes that are most significantly perturbed in the dataset of interest.

The key components of the IPA Core Analysis are:

• Signaling and Metabolic Pathways Analysis
• Cellular and Disease Process Analysis
• Molecular Network Analysis
• Contextual Data Analysis

These capabilities enable researchers to:

• Analyze data in the context of molecular mechanisms
• Relate molecular events to higher-order cellular and disease processes
• Relate molecular changes to organismal physiology and pathophysiology
• Visualize time course and dose response effects
• Interpret and integrate data from multiple platforms (e.g., genomics, proteomics, genotyping, miRNA) and with mixed identifiers
• Quickly focus on analysis results that are most closely aligned with your experimental model or question
• Compare affected pathways and phenotypes across platform, time, dose, or patient population

IPA-Tox™ Analysis
IPA-Tox uses Toxicity Functions in combination with Toxicity Lists to link experimental data to clinical pathology endpoints, understand pharmacological response, and support mechanism of action and mechanism of toxicity hypothesis generation.

IPA-Biomarker™ Analysis
IPA-Biomarker identifies the most biologically relevant and promising molecular biomarker candidates from datasets generated at every step of the drug discovery process.

IPA-Metabolomics ™ Analysis
IPA-Metabolomics overcomes the metabolomics data analysis challenge by providing the critical context necessary to gain biological insight into cell physiology and metabolism from metabolite data.

Data Upload Wizard
Quickly upload data from multiple formats without time-consuming data formatting steps. Compare or analyze datasets from multiple experimental platforms with mixed gene and protein identifiers.

Analysis Summaries
Creates an automated, focused, and summarized output of analysis results that can easily be emailed as an interactive PDF document.

Supported Species:
IPA supports the upload and analysis of human, mouse, rat, and canine identifiers. Additionally, IPA supports analysis of molecular data for the following species through ortholog mapping of Entrez Gene IDs:

• Cow
• Chimp
• Chicken
• Rhesus macaque monkey
• Plant (Arabidopsis thaliana)
• Yeast (Saccharomyces cerevisiae)
• Fly (Drosophila melanogaster)
• Worm (Caenorhabditis elegans)
• Zebrafish (Danio rerio)

Researchers can now avoid the time-consuming and manual mapping process formerly needed for analyzing data sets from these animal models. Predicted pathway modeling of data generated from these species enables biological interpretation. IPA supports the mapping of Entrez Gene ID's,GenBank, Refseq, and GenPept ID's. In addition, microarray ID mapping is supported for a subset of the new species.

Communicate and Collaborate

IPA's tools and pathways are a quick and valuable way to share hypotheses and insights with other research teams and collaborators. Integrate knowledge from multiple sites and data repositories and easily share findings of interest in order to streamline the workflow and communicate more easily with colleagues.

Share
Easily invite collaborators to review and integrate analysis results, dataset files, analysis summaries, and pathways.

Report
Export results, tables of annotations, bibliographies, interactive analysis summaries, Pathway and List Reports, and high-resolution images to include in reports and presentations. Reference export management allows you to export references into EndNote or other formats.

Path Designer
Transform your networks and pathways in IPA into publication-quality pathway graphics rich with color, customized text and fonts, biological icons, organelles, and custom backgrounds.

• Expand and explore pathways using the high quality content stored in IPA.
• Complete your entire workflow - from data analysis to data sharing and publication - within IPA.
• Quickly create custom graphics with an intuitive and easy-to-use interface.

Interactive Pathways

Insert fully referenced pathways that provide access to the underlying biological information into e-mails or presentations.

Integrate with in-house software applications or 3rd party software tools
The IPA Integration Module enables life science researchers to access the high quality, detail-rich biological and chemical knowledge in IPA directly from their internal websites, applications, and gene catalogues, as well as from internal research reports, e-mails and other shared documents that are part of their daily research workflows. This easy-to-implement module increases the utility of internal web sites, search portals, and research reports by providing direct links to the content and analysis capabilities in IPA.

Click here to read more, or download the whitepaper.

	Content IPA uses the Ingenuity Knowledge Base, a repository of Findings that describe molecular interactions, regulatory events, gene to phenotype associations, and chemical knowledge that provide the building blocks for pathway construction. It is the largest knowledge base of its kind, with millions of Findings curated from the full text of the life sciences literature by PhD life scientists, and features the most descriptive and detailed structure, the highest degree of accuracy, and the largest number of experimentally-demonstrated Findings from the literature. The Ingenuity Knowledge Base is used as a starting point for exploration and a bridge between novel discovery and known biology. It provides researchers with a tremendous resource for searching relevant and substantiated knowledge from the literature, and for interpreting experimental results in the context of larger biological systems for greater confidence with research decisions. Biological and Chemical Information The Ingenuity Knowledge Base includes modeled relationships between chemicals, proteins, genes, mutations, complexes, cells, cellular components, tissues, drugs, cellular processes, diseases and clinical phenotypes. Additional Sources Beyond Literature Findings In addition to expert extraction of findings from the literature, IPA includes content from high quality databases such as: Entrez Gene RefSeq OMIM GWAS Database Gene Ontology Human Metabolome Database (HMDB) GNF Tissue Expression Body Atlas NCI-60 Cell Line Expression Atlas KEGG metabolic pathway information LIGAND enzyme/substrate reactions BIND, DIP, MINT, MIPS, BIOGRID, INTACT, COGNIA protein-protein interactions (updated) ARGONAUTE 2, TARBASE microRNA-mRNA targeting interactions Clinicaltrials.gov Drugs@FDA.gov Mosby’s Drug Consult Goodman & Gilman's 'Pharmacological Basis of Therapeutics' DrugBank IPA also contains key Findings and relationships manually curated by Ingenuity scientists that describe: FDA approved drugs and clinical candidates Cell Signaling, Metabolic, and Disease Pathways Toxicity Lists and Pathways Predicted and experimentally demonstrated microRNA targets Gene, protein, and compound associations with disease Manually Curated Information The vast majority of Findings in IPA are manually curated and modeled by a team of Ph.D. scientists from primary literature sources, including peer-reviewed journal articles, review articles, and textbooks. Unparalleled Structure and Contextual Details The content in IPA contains a tremendous amount of contextual detail such as species specificity, cell type context, mutations, post-translational modification sites, epigenetic modifications, and experimental methods used. The organizational structure ensures semantic and linguistic consistency, the resolution of synonyms, the integration and mapping of content from multiple sources, and the inference of novel relationships. Frequent Updates The findings in IPA are updated regularly to provide customers with high impact knowledge on a timely basis. Findings that populate Gene Views, Chem Views, and Molecular Networks are updated weekly. Full releases of the Ingenuity Knowledge Base to IPA are provided quarterly.

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