Ingenuity Pathways Analysis (IPA)

Capabilities

Search and Explore Biological and Chemical Knowledge

IPA's Search & Explore capabilities offer researchers access to the most current knowledge 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 working 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 targeted hypotheses by using molecule or relationship filters to leverage only the findings related to your experimental model
• Understand the biological effects of chemicals

With the new, expanded chemical content, search for genes or chemicals that are:

• 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 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, 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.
• Drill down to the supporting evidence 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.

My Pathways & Lists
Build custom libraries of pathways representing 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 Grow and Connect tools to edit and expand networks based on the molecular relationships most relevant to the project:
  • Transcriptional networks o Phosphorylation cascades
  • Protein-Protein of Protein-DNA Interaction 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.

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.

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
• Understand the relevance to organismal physiology and pathophysiology
• Visualize time course and dose response effects
• Interpret and integrate data from multiple platforms (e.g., genomics, proteomics, genotyping) and with mixed identifiers
• Quickly focus on analysis results that are most closely aligned with your experimental model or question

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 uploads data from multiple formats without time-consuming data formatting steps. Analyze datasets 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 human, mouse, rat, and canine identifiers. Additionally, IPA supports 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, and high-resolution images to include in reports and presentations. Reference export management allows you to export references into EndNote or other formats.

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 Ingenuity's Knowledge Base, a repository of 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 pulled 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 literature findings. 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 IPA's extensive knowledge base includes modeled relationships between chemicals, proteins, genes, 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: EntrezGene RefSeq OMIM Gene Ontology Gene Expression Body Atlas from GNF Tissue Expression Body Atlas NCI-60 Cell Line Expression Atlas KEGG metabolic pathway information LIGAND enzyme/substrate reactions BIND, DIP, MIPS, IntAct, Biogrid, MINT, interactome studies (Y2H) IPA also contains key findings and relationships curated by Ingenuity scientists that describe: FDA approved drugs and clinical candidates Cell Signaling Pathways Toxicity Lists and Pathways Predicted and experimentally demonstrated mRNA targets Manually Curated Information All of the information in IPA is 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 content in IPA is updated regularly to provide customers with high-impact knowledge on a timely basis.

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