Ingenuity Pathways Analysis (IPA)

The Ingenuity Knowledge Base

	Overview The Ingenuity Knowledge Base is a repository of molecular interactions, regulatory events, gene-to-phenotype associations, and chemical knowledge that provides 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 Ph.D.-level life scientists, and features the most descriptive and detailed structure, and the highest degree of accuracy. Ingenuity's Knowledge Base is used as a starting point for exploration of biological and chemical systems 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. The Ingenuity Knowledge Base provides: Integrated, broad coverage of systems biology knowledge including relationships between proteins, genes, protein complexes, cells, cellular components, tissues, organs, small molecules, cellular phenotypes, and disease processes Gene View pages with comprehensive, species-specific knowledge about gene function and regulation, tissue and cell line expression patterns, subcellular location, mutations, and disease associations Chemical and drug information for clinical candidates and FDA-approved drugs Millions of physical interactions and regulatory events extracted from literature Semantic and linguistic consistency based on Ingenuity's comprehensive ontology Synonym and homonym mapping to maintain object identity and remove duplicate objects Representation of biological context, including species specificity, localization, mutations, epigenetic modifications, and experimental conditions Systematic capture of canonical pathway relationships

	Highlights Expert Extraction: All relationships are manually curated and modeled by a team of Ph.D. scientists, and are supported by experimental evidence published in the peer-reviewed literature. Breadth of Knowledge: The Knowledge Base houses millions of relationships between proteins, genes, complexes, cells, tissues, drugs, and diseases. Biological Context: Strict content extraction protocols require inclusion of details regarding cellular context, mutations, protein and promoter domains, species, tissues, and the net effect on the process or phenotype being studied. Consistent Modeling: Ingenuity's proprietary ontology tools and protocols ensure consistent modeling of biological and chemical knowledge, enabling rapid development of computational solutions. Frequent Updates: Regular updates provide customers with high-impact content from over 300 journals, review articles, textbooks, and external databases such as OMIM, GO, and EntrezGene, as well as manually curated canonical pathways and drug/target/disease relationships.

Quality Content
The information in the Ingenuity Knowledge Base includes modeled relationships between proteins, genes, complexes, cells, tissues, drugs, and diseases. Each modeled relationship originates from reported experimental findings from various primary literature sources, including peer-reviewed journal articles, review articles, and textbooks. In addition to literature findings, the Ingenuity Knowledge Base includes many other types of content including findings and annotations from major NCBI databases (EntrezGene, RefSeq, OMIM disease associations), targets and pharmacological relevance of FDA approved and clinical trial drugs, Gene Ontology annotations, a normal gene expression body atlas for over 30 tissues and the NCI-60 panel of cancer cell lines, KEGG and LIGAND metabolic pathways and reactions, cell signaling pathways, and more. It also includes content from BIND, DIP, MIPS, IntAct, Biogrid, MINT, and interactome studies (Y2H).

Manual Curation
Ingenuity's unique content extraction and modeling process employs a rigorous quality assurance protocol to ensure that literature findings are incorporated into the knowledge base with the accuracy and detail needed to ensure successful biological inference, modeling, and prediction. To obtain each finding, Ph.D.-level scientists read the full text primary source, then extract findings substantiated by experimental evidence and report each finding using a highly descriptive, controlled vocabulary. This process involves breaking down a finding into its logical components, then modeling each component and the reported relationship between components along with the contextual experimental parameters (e.g., species type, cell type, experimental method, etc.). This modeling process captures not only relationships between biological objects, but also important contextual details that enable more sophisticated biological queries.The components, relationships, and contextual details are then deposited within the Ingenuity Knowledge Base, where they are computationally accessed to drive the features and solutions in IPA. Created by Ingenuity's founders at Stanford University, this unique knowledge acquisition and modeling process is protected by eight (8) US Patents.

Structured Knowledge
The structure of the Ingenuity Knowledge Base is provided by the Ingenuity Ontology, which contains hundreds of thousands of unique concepts (such as macromolecules, interaction types, functions, processes, species, diseases) that enforce semantic and linguistic consistency across all the reported literature findings. This ontology preserves object identity across findings, resolves synonym and homonym confusion, and integrates data sources for more accurate relationship representation. The result is a knowledge base characterized by consistent, accurate, and detailed information that enables life scientists to quickly generate novel biological insights.

Chemical Content
Ingenuity's Knowledge Base contains knowledge on thousands of compounds, including endogenous chemicals and metabolites, FDA-approved drugs and clinical candidates, and exogenous chemicals and toxicants. This information allows researchers to understand and visualize the biological impact of these compounds, including:

• Interaction with target proteins, regulation of target protein activity, phosphorylation, and expression
• Impact on non-target proteins and on molecular, cellular and disease processes
• Participation in signaling and metabolic pathways
• Toxicity and therapeutic information
• Compound regulation of P450 enzyme expression and activity
• Bioavailability, plasma binding, LD50, IC50, PK/PD, AUC, and metabolism
• Mutagenicity data
• CAS number
• Synonyms (including systematic name and brand names)
• Chemical formula and SMILES notation

Toxicology Content
The Ingenuity Knowledge Base features a large collection of knowledge from the molecular toxicology literature describing the pharmacological and toxicological effects of chemicals in vitro and in vivo.

Here are a few highlights from the collection of toxicity pathways and lists in Ingenuity's knowledge base:

New Updates
With the release of IPA 6.3, the content in the Ingenuity Knowledge Base has been updated to incorporate new expert-extracted biological and chemical information from the scientific literature on the following pathways:

• 14-3-3-mediated Signaling
• Alpha-Adrenergic Signaling
• Erythropoietin Signaling
• RAR Activation
• Role of BRCA1 in DNA Damage Response
• BMP Signaling

IPA 6.3 also includes content updates for:

• Drug information such as manufacturer, clinical trial sponsor, date of last clinical trial update, and link to NCT website
• Protein-protein interactions Additional Protein-Protein Interaction Content based on external database imports, >80K findings, includes: BIND, DIP, MIPS, IntAct, Biogrid, MINT, Interactome studies (Y2H)

»Top of Page