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A Knowledge Graph Approach to Elucidate the Role of Organellar Pathways in Disease via Biomedical Reports
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Knowledge graph-driven curation of heme-TLR4 interactions in inflammatory pathways.

Dhruv C Rathod1, Negin Sadat Babaiha2, Elena Kullmann1

  • 1Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, Bonn, Germany.

Journal of Inorganic Biochemistry
|August 27, 2025
PubMed
Summary
This summary is machine-generated.

Labile heme activates inflammatory pathways via Toll-like receptor 4 (TLR4). This study expands the Heme Knowledge Graph (HemeKG) to include new heme-TLR4 interactions, improving understanding of inflammation and metabolic dysregulation.

Keywords:
HemeHemolysisKnowledge graphSignaling pathwaysTLR4

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Area of Science:

  • Biochemistry
  • Immunology
  • Bioinformatics

Background:

  • Heme is an iron-containing molecule crucial for oxygen transport and electron transfer.
  • Heme also functions as an extracellular signaling molecule, modulating inflammatory responses.
  • Elevated heme levels can trigger inflammatory signaling, particularly via Toll-like receptor 4 (TLR4).

Purpose of the Study:

  • To systematically expand the Heme Knowledge Graph (HemeKG) with recent findings on heme-TLR4 interactions.
  • To integrate newly identified molecular entities involved in heme-mediated inflammation.
  • To provide an enhanced platform for understanding heme-driven inflammatory pathways.

Main Methods:

  • Literature curation and validation using Biological Expression Language (BEL) standards.
  • Integration of new molecular entities (AP-1, IL-12, CD80, CD86, CXCL1) into the HemeKG.
  • Pathway enrichment analysis using KEGG, Reactome, and WikiPathways databases.

Main Results:

  • Successfully integrated novel molecular entities into the HemeKG framework.
  • Pathway enrichment analysis confirmed significant involvement of the TLR4 signaling cascade.
  • The updated HemeKG enhances the representation of heme-TLR4 interactions.

Conclusions:

  • The expanded HemeKG offers an integrated and predictive resource for studying heme-TLR4 signaling.
  • This work deepens the understanding of how heme influences inflammatory responses.
  • The findings contribute to insights into metabolic dysregulation linked to heme-driven inflammation.