CTD Tetramers

CTD Tetramers generates CGPD-tetramers from manually curated CTD interactions to link Chemicals, Genes, Phenotypes, and Diseases for elucidating molecular mechanisms of environmental exposures.

Key Features:

• Integration of Curated Data: Uses manually curated, literature-based interactions from the Comparative Toxicogenomics Database (CTD) so each tetramer component is evidence-based.
• CGPD-tetramer Structure: Represents information as four-unit blocks linking a Chemical exposure to an interacting Gene, a resultant Phenotype, and a Disease outcome.
• Construction of Detailed Mechanisms: Assembles multiple tetramers to construct modes-of-action that detail pathways through which chemicals induce diseases.
• Informing Adverse Outcome Pathways (AOPs): Maps adverse outcome terms to corresponding CTD terms to augment AOPs with additional stressors, genes, and phenotypes.
• Application Across Diverse Chemicals and Conditions: Demonstrates applicability with environmental chemicals such as perfluoroalkyl substances and bisphenol A, and phenotypes and diseases including apoptosis, spermatogenesis, asthma, obesity, and male infertility.

Scientific Applications:

• Elucidating molecular mechanisms: Links chemical exposures to gene-level interactions, phenotypes, and disease outcomes to clarify step-wise molecular mechanisms.
• Augmenting AOPs: Provides tetramer-based evidence to expand and refine adverse outcome pathways by adding stressors, genes, and phenotypes.
• Hypothesis generation and datasets: Produces computational datasets supported by curated evidence to generate testable hypotheses about environmental health effects.
• Chemical-specific analyses: Supports investigation of specific environmental chemicals (e.g., perfluoroalkyl substances, bisphenol A) and associated phenotypes and diseases.

Methodology:

Generates CGPD-tetramers from manually curated, literature-based CTD interactions by linking a Chemical to a Gene, a Phenotype, and a Disease; maps adverse outcome terms to CTD terms and assembles multiple tetramers to construct modes-of-action and provide computational datasets.