Heme-triggered effects on blood coagulation: a bioinformatics approach based on experimental data

Introduction A considerable amount of heme is released under hemolytic conditions and thus causes pathological states such as thrombosis, by either binding to plasma proteins or interaction with distinct cells. The huge number of publications describing these effects, including the apparently contradictory observations, cannot be managed anymore in a traditional way to close knowledge gaps and deepen our understanding of heme-driven coagulopathies with the aim to develop suitable and specific treatment strategies. A computational approach and exploration of the complex network of heme-triggered effects in the blood coagulation system is therefore useful.

Method Herein, the knowledge available so far concerning heme-triggered effects on blood coagulation was curated and modeled in a mechanistic interactome. The data were incorporated in an earlier established heme knowledge graph, “HemeKG”, to better comprehend the existing data on heme biology.

Results A pathway enrichment analysis of these data provided insights into hitherto unknown connections and novel experimental targets within the blood coagulation cascade and platelet activation pathways.

Conclusion This curated knowledge will support further investigation of the prothrombotic nature of heme in the future, since our study allows, for the first time, a detailed network analysis of the effects of heme in blood coagulation.

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Artikel online veröffentlicht:
20. Februar 2023