Exploring the Complex Network of Heme-Triggered Effects on the Blood Coagulation System

Area of Science:

• Biochemistry and Molecular Biology
• Hematology
• Computational Biology

Background:

• Excess labile heme during hemolysis modulates the blood coagulation system, promoting prothrombotic states through interactions with plasma proteins and cellular components.
• Existing knowledge on heme's procoagulant effects is fragmented, with contradictory findings and significant gaps, hindering a comprehensive understanding of heme-driven coagulopathies and therapeutic development.

Purpose of the Study:

• To computationally explore the complex network of heme-triggered effects within the blood coagulation system.
• To integrate heme-specific and hemostasis terminology into a mechanistic interactome and the HemeKG knowledge graph.
• To identify novel experimental targets and understand heme's prothrombotic role in coagulation and platelet activation.

Main Methods:

• Curated and modeled existing knowledge on heme-coagulation interactions into a mechanistic interactome.
• Integrated the interactome data into the established HemeKG knowledge graph.
• Performed pathway enrichment analysis on the integrated data to uncover novel links and targets.

Main Results:

• Developed a detailed mechanistic interactome of heme's effects on blood coagulation.
• Successfully integrated heme-coagulation data into the HemeKG, enhancing the understanding of heme biology.
• Pathway enrichment analysis revealed previously unknown connections within coagulation and platelet activation pathways.

Conclusions:

• This study provides the first detailed network analysis of heme's impact on the blood coagulation system.
• The findings offer novel insights into the prothrombotic nature of heme and identify potential therapeutic targets.
• The developed interactome and integrated knowledge graph serve as a foundation for future research into heme-driven coagulopathies.