Annotating cancer variants and anti-cancer therapeutics in reactome

Area of Science:

• Biochemistry
• Molecular Biology
• Bioinformatics

Background:

• Reactome models biological pathways as chemical reactions mirroring cellular interactions.
• Existing Reactome data structures require extension to incorporate disease-specific information, particularly for cancer.

Purpose of the Study:

• To extend the Reactome data model for annotating cancer and other disease processes.
• To enhance pathway visualization and analysis tools for disease variants.

Main Methods:

• Extended the protein modification class to include amino acid sequence changes and fusion proteins relevant to disease.
• Added a disease attribute to reaction, pathway, and physical entity classes, utilizing disease ontology terms.
• Adapted the Pathway Browser for graphical representation and comparison of disease variants with wild-type pathways.

Main Results:

• The extended Reactome model now accommodates annotation of disease-related protein alterations.
• Disease attributes integrated into Reactome allow for specific tracking of disease pathways.
• The Pathway Browser visualizes cancer pathway variants, their connections to other pathways, and therapeutic interventions.

Conclusions:

• Reactome's data model extensions facilitate comprehensive annotation of cancer pathways.
• These enhancements enable interoperability with existing pathway and network analysis tools.
• The updated Reactome system provides insights into altered biological behavior in diseases like cancer, aiding therapeutic development.