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@ARTICLE{Iyappan:138638,
author = {Iyappan, Anandhi and Gündel, Michaela and Shahid, Mohammad
and Wang, Jiali and Li, Hui and Mevissen, Heinz-Theodor and
Müller, Bernd and Fluck, Juliane and Jirsa, Viktor and
Domide, Lia and Younesi, Erfan and Hofmann-Apitius, Martin},
title = {{T}owards a {P}athway {I}nventory of the {H}uman {B}rain
for {M}odeling {D}isease {M}echanisms {U}nderlying
{N}eurodegeneration.},
journal = {Journal of Alzheimer's disease},
volume = {52},
number = {4},
issn = {1387-2877},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {DZNE-2020-04960},
pages = {1343-1360},
year = {2016},
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.},
keywords = {Brain: drug effects / Brain: metabolism / Brain:
physiopathology / Databases, Factual / Humans / Metabolic
Networks and Pathways: physiology / Models, Neurological /
Neurodegenerative Diseases: metabolism / Neurodegenerative
Diseases: physiopathology / Signal Transduction: physiology
/ Terminology as Topic},
cin = {AG Breteler},
ddc = {610},
cid = {I:(DE-2719)1012001},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27079715},
doi = {10.3233/JAD-151178},
url = {https://pub.dzne.de/record/138638},
}