CBM KG: A Comorbidity-Centric Knowledge Graph Uncovering Causal Pathomechanisms Between COVID-19 and Neurodegenerative Diseases

Atas Guvenilir, H.; Sethumadhavan, P.; Kaladharan, A.; Vieira de Sa, R.; Sridhar, A.; Haferkamp, U.; Pless, O.; Marti-Sarrias, A.; Acosta, S.; Letoha, T.; Hudak, A.; Ohnmacht, J.; Hefeng, F. Q.; Hofmann-Apitius, M.; Tom Kodamullil, A.

doi:10.1101/2025.08.18.670790

bioRxiv · 10.1101/2025.08.18.670790

CBM KG: A Comorbidity-Centric Knowledge Graph Uncovering Causal Pathomechanisms Between COVID-19 and Neurodegenerative Diseases

Atas Guvenilir, H.·Sethumadhavan, P.·Kaladharan, A.·Vieira de Sa, R.·Sridhar, A.·Haferkamp, U.·Pless, O.·Marti-Sarrias, A.·Acosta, S.·Letoha, T.·Hudak, A.·Ohnmacht, J.·Hefeng, F. Q.·Hofmann-Apitius, M.·Tom Kodamullil, A.

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Abstract

SummaryCOVID-19 is increasingly recognized as a potential trigger or accelerator of neurodegenerative diseases such as Alzheimers and Parkinsons. To systematically explore the putative molecular and clinical associations between them, we present CBM KG (Causal Biological Mechanisms Knowledge Graph)--a manually curated, comorbidity-centric resource developed within the EU-funded COMMUTE project. CBM KG integrates over 2,800 cause-and-effect or correlative relationships from 63 peer-reviewed publications, highlighting key mechanisms such as viral entry routes, blood-brain barrier alteration, microglial activation, neuroinflammation, and APOE {varepsilon}4-associated susceptibility. Each relationship in the graph is fully traceable to its source evidence, ensuring transparency and reproducibility. Unlike general-purpose or single disease-focused knowledge graphs, CBM KG is specifically designed to represent causal biological mechanisms spanning both infectious and neurodegenerative processes. By encoding directional, cause-and-effect relationships, it supports the interpretation of clinical co-occurrences through plausible mechanistic links between overlapping disease pathways, offering high-resolution insights at both molecular and clinical levels. Availability and implementationThe BEL files, Neo4j database, and Cytoscape visualization files are publicly available at: https://github.com/SCAI-BIO/CBM-Comorbidity-KG.

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Atas Guvenilir, H., Sethumadhavan, P., Kaladharan, A., Vieira de Sa, R., Sridhar, A., Haferkamp, U., Pless, O., Marti-Sarrias, A., Acosta, S., Letoha, T., Hudak, A., Ohnmacht, J., Hefeng, F. Q., Hofmann-Apitius, M., Tom Kodamullil, A.. 2025-08-19. CBM KG: A Comorbidity-Centric Knowledge Graph Uncovering Causal Pathomechanisms Between COVID-19 and Neurodegenerative Diseases. https://doi.org/10.1101/2025.08.18.670790

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