Journal Article

DZNE-2020-04960

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Towards a Pathway Inventory of the Human Brain for Modeling Disease Mechanisms Underlying Neurodegeneration.

Iyappan, A. ; Gündel, M. ; Shahid, M.DZNE* ; Wang, J. ; Li, H. ; Mevissen, H.-T. ; Müller, B. ; Fluck, J. ; Jirsa, V. ; Domide, L. ; Younesi, E. ; Hofmann-Apitius, M.

2016
IOS Press Amsterdam

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Please use a persistent id in citations: doi:10.3233/JAD-151178  doi:10.1016/0167-5273(89)90276-3

Abstract: Molecular signaling pathways have been long used to demonstrate interactions among upstream causal molecules and downstream biological effects. They show the signal flow between cell compartments, the majority of which are represented as cartoons. These are often drawn manually by scanning through the literature, which is time-consuming, static, and non-interoperable. Moreover, these pathways are often devoid of context (condition and tissue) and biased toward certain disease conditions. Mining the scientific literature creates new possibilities to retrieve pathway information at higher contextual resolution and specificity. To address this challenge, we have created a pathway terminology system by combining signaling pathways and biological events to ensure a broad coverage of the entire pathway knowledge domain. This terminology was applied to mining biomedical papers and patents about neurodegenerative diseases with focus on Alzheimer's disease. We demonstrate the power of our approach by mapping literature-derived signaling pathways onto their corresponding anatomical regions in the human brain under healthy and Alzheimer's disease states. We demonstrate how this knowledge resource can be used to identify a putative mechanism explaining the mode-of-action of the approved drug Rasagiline, and show how this resource can be used for fingerprinting patents to support the discovery of pathway knowledge for Alzheimer's disease. Finally, we propose that based on next-generation cause-and-effect pathway models, a dedicated inventory of computer-processable pathway models specific to neurodegenerative diseases can be established, which hopefully accelerates context-specific enrichment analysis of experimental data with higher resolution and richer annotations.

Keyword(s): Brain: drug effects (MeSH) ; Brain: metabolism (MeSH) ; Brain: physiopathology (MeSH) ; Databases, Factual (MeSH) ; Humans (MeSH) ; Metabolic Networks and Pathways: physiology (MeSH) ; Models, Neurological (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Neurodegenerative Diseases: physiopathology (MeSH) ; Signal Transduction: physiology (MeSH) ; Terminology as Topic (MeSH)

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Contributing Institute(s):

1. Population Health Sciences (AG Breteler)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2016

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Database coverage:
; ; BIOSIS Previews ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; IF < 5 ; JCR ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Science Citation Index Expanded ; Web of Science Core Collection ; Web of Science Core Collection

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