TY  - JOUR
A1  - Kringel, Dario
A1  - Ultsch, Alfred
A1  - Zimmermann, Michael
A1  - Jansen, Peter
A1  - Ilias, Wilfried
A1  - Freynhagen, Rainer
A1  - Griessinger, Norbert
A1  - Kopf, Andreas
A1  - Stein, Christoph
A1  - Doehring, Alexandra
A1  - Resch, Eduard
A1  - Lötsch, Jörn
T1  - Emergent biomarker derived from next-generation sequencing to identify pain patients requiring uncommonly high opioid doses
T2  - The pharmacogenomics journal
N2  - Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces ‘big data’ exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80.6±4%. This outperformed alternative classifiers such as reportedly functional opioid receptor gene variants or complex biomarkers obtained via multiple regression or decision tree analysis. The accumulation of several genetic variants with only minor functional influences may result in a qualitative consequence affecting complex phenotypes, pointing at emergent properties in genetics.
KW  - Clinical genetics
KW  - Genetics research
KW  - Predictive medicine
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46552
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-465524
SN  - 1470-269X
SN  - 1473-1150
N1  - This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
VL  - [16]
IS  - 5
SP  - 1
EP  - 8
PB  - Nature Publishing Group
CY  - Basingstoke
ER  -