TY  - JOUR
AU  - Iyappan, Anandhi
AU  - Gündel, Michaela
AU  - Shahid, Mohammad
AU  - Wang, Jiali
AU  - Li, Hui
AU  - Mevissen, Heinz-Theodor
AU  - Müller, Bernd
AU  - Fluck, Juliane
AU  - Jirsa, Viktor
AU  - Domide, Lia
AU  - Younesi, Erfan
AU  - Hofmann-Apitius, Martin
TI  - Towards a Pathway Inventory of the Human Brain for Modeling Disease Mechanisms Underlying Neurodegeneration.
JO  - Journal of Alzheimer's disease
VL  - 52
IS  - 4
SN  - 1387-2877
CY  - Amsterdam
PB  - IOS Press
M1  - DZNE-2020-04960
SP  - 1343-1360
PY  - 2016
AB  - 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.
KW  - Brain: drug effects
KW  - Brain: metabolism
KW  - Brain: physiopathology
KW  - Databases, Factual
KW  - Humans
KW  - Metabolic Networks and Pathways: physiology
KW  - Models, Neurological
KW  - Neurodegenerative Diseases: metabolism
KW  - Neurodegenerative Diseases: physiopathology
KW  - Signal Transduction: physiology
KW  - Terminology as Topic
LB  - PUB:(DE-HGF)16
C6  - pmid:27079715
DO  - DOI:10.3233/JAD-151178
UR  - https://pub.dzne.de/record/138638
ER  -