The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research
BackgroundAs global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease’s etiology...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
JMIR Publications
2024-04-01
|
Series: | Journal of Medical Internet Research |
Online Access: | https://www.jmir.org/2024/1/e46777 |
_version_ | 1797201450226417664 |
---|---|
author | Joseph D Romano Van Truong Rachit Kumar Mythreye Venkatesan Britney E Graham Yun Hao Nick Matsumoto Xi Li Zhiping Wang Marylyn D Ritchie Li Shen Jason H Moore |
author_facet | Joseph D Romano Van Truong Rachit Kumar Mythreye Venkatesan Britney E Graham Yun Hao Nick Matsumoto Xi Li Zhiping Wang Marylyn D Ritchie Li Shen Jason H Moore |
author_sort | Joseph D Romano |
collection | DOAJ |
description |
BackgroundAs global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease’s etiology and response to drugs.
ObjectiveWe designed the Alzheimer’s Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics.
MethodsWe designed the AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (eg, chemicals, genes, anatomy, and diseases). AlzKB uses a Web Ontology Language 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base.
ResultsAlzKB is freely available on the web and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we used graph data science and machine learning to (1) propose new therapeutic targets based on similarities of AD to Parkinson disease and (2) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones.
ConclusionsAlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through 2 use cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge. |
first_indexed | 2024-04-24T07:47:44Z |
format | Article |
id | doaj.art-484c4a7497fd40b4bfb9252d73687d5c |
institution | Directory Open Access Journal |
issn | 1438-8871 |
language | English |
last_indexed | 2024-04-24T07:47:44Z |
publishDate | 2024-04-01 |
publisher | JMIR Publications |
record_format | Article |
series | Journal of Medical Internet Research |
spelling | doaj.art-484c4a7497fd40b4bfb9252d73687d5c2024-04-18T16:30:32ZengJMIR PublicationsJournal of Medical Internet Research1438-88712024-04-0126e4677710.2196/46777The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease ResearchJoseph D Romanohttps://orcid.org/0000-0002-7999-4399Van Truonghttps://orcid.org/0000-0002-5485-1818Rachit Kumarhttps://orcid.org/0000-0002-7736-3307Mythreye Venkatesanhttps://orcid.org/0000-0001-9946-0688Britney E Grahamhttps://orcid.org/0000-0002-5417-3957Yun Haohttps://orcid.org/0009-0004-6198-3060Nick Matsumotohttps://orcid.org/0000-0002-3280-9678Xi Lihttps://orcid.org/0009-0006-4205-0729Zhiping Wanghttps://orcid.org/0000-0002-3796-3164Marylyn D Ritchiehttps://orcid.org/0000-0002-1208-1720Li Shenhttps://orcid.org/0000-0002-5443-0503Jason H Moorehttps://orcid.org/0000-0002-5015-1099 BackgroundAs global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease’s etiology and response to drugs. ObjectiveWe designed the Alzheimer’s Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. MethodsWe designed the AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (eg, chemicals, genes, anatomy, and diseases). AlzKB uses a Web Ontology Language 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base. ResultsAlzKB is freely available on the web and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we used graph data science and machine learning to (1) propose new therapeutic targets based on similarities of AD to Parkinson disease and (2) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones. ConclusionsAlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through 2 use cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge.https://www.jmir.org/2024/1/e46777 |
spellingShingle | Joseph D Romano Van Truong Rachit Kumar Mythreye Venkatesan Britney E Graham Yun Hao Nick Matsumoto Xi Li Zhiping Wang Marylyn D Ritchie Li Shen Jason H Moore The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research Journal of Medical Internet Research |
title | The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research |
title_full | The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research |
title_fullStr | The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research |
title_full_unstemmed | The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research |
title_short | The Alzheimer’s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research |
title_sort | alzheimer s knowledge base a knowledge graph for alzheimer disease research |
url | https://www.jmir.org/2024/1/e46777 |
work_keys_str_mv | AT josephdromano thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT vantruong thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT rachitkumar thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT mythreyevenkatesan thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT britneyegraham thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT yunhao thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT nickmatsumoto thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT xili thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT zhipingwang thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT marylyndritchie thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT lishen thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT jasonhmoore thealzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT josephdromano alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT vantruong alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT rachitkumar alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT mythreyevenkatesan alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT britneyegraham alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT yunhao alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT nickmatsumoto alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT xili alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT zhipingwang alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT marylyndritchie alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT lishen alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch AT jasonhmoore alzheimersknowledgebaseaknowledgegraphforalzheimerdiseaseresearch |