TY  - JOUR
A1  - Kringel, Dario
A1  - Malkusch, Sebastian
A1  - Kalso, Eija
A1  - Lötsch, Jörn
T1  - Computational functional genomics-based AmpliSeq™ panel for next-generation sequencing of key genes of pain
T2  - International journal of molecular sciences
N2  - The genetic background of pain is becoming increasingly well understood, which opens up possibilities for predicting the individual risk of persistent pain and the use of tailored therapies adapted to the variant pattern of the patient’s pain-relevant genes. The individual variant pattern of pain-relevant genes is accessible via next-generation sequencing, although the analysis of all “pain genes” would be expensive. Here, we report on the development of a cost-effective next generation sequencing-based pain-genotyping assay comprising the development of a customized AmpliSeq™ panel and bioinformatics approaches that condensate the genetic information of pain by identifying the most representative genes. The panel includes 29 key genes that have been shown to cover 70% of the biological functions exerted by a list of 540 so-called “pain genes” derived from transgenic mice experiments. These were supplemented by 43 additional genes that had been independently proposed as relevant for persistent pain. The functional genomics covered by the resulting 72 genes is particularly represented by mitogen-activated protein kinase of extracellular signal-regulated kinase and cytokine production and secretion. The present genotyping assay was established in 61 subjects of Caucasian ethnicity and investigates the functional role of the selected genes in the context of the known genetic architecture of pain without seeking functional associations for pain. The assay identified a total of 691 genetic variants, of which many have reports for a clinical relevance for pain or in another context. The assay is applicable for small to large-scale experimental setups at contemporary genotyping costs.
KW  - next generation sequencing
KW  - human genomics
KW  - pain genetics
KW  - pharmacogenomics
KW  - computational functional genomics
KW  - data science
KW  - knowledge discovery
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57760
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-577608
SN  - 1422-0067
N1  - © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
VL  - 22
IS  - art. 878
SP  - 1
EP  - 33
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -