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  4. Combinatorial expression rules of ion channel genes in juvenile rat (Rattus norvegicus) neocortical neurons
 
research article

Combinatorial expression rules of ion channel genes in juvenile rat (Rattus norvegicus) neocortical neurons

Khazen, Georges  
•
Hill, Sean L
•
Schürmann, Felix  
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2012
PloS One

The electrical diversity of neurons arises from the expression of different combinations of ion channels. The gene expression rules governing these combinations are not known. We examined the expression of twenty-six ion channel genes in a broad range of single neocortical neuron cell types. Using expression data from a subset of twenty-six ion channel genes in ten different neocortical neuronal types, classified according to their electrophysiological properties, morphologies and anatomical positions, we first developed an incremental Support Vector Machine (iSVM) model that prioritizes the predictive value of single and combinations of genes for the rest of the expression pattern. With this approach we could predict the expression patterns for the ten neuronal types with an average 10-fold cross validation accuracy of 87% and for a further fourteen neuronal types not used in building the model, with an average accuracy of 75%. The expression of the genes for HCN4, Kv2.2, Kv3.2 and Caβ3 were found to be particularly strong predictors of ion channel gene combinations, while expression of the Kv1.4 and Kv3.3 genes has no predictive value. Using a logic gate analysis, we then extracted a spectrum of observed combinatorial gene expression rules of twenty ion channels in different neocortical neurons. We also show that when applied to a completely random and independent data, the model could not extract any rules and that it is only possible to extract them if the data has consistent expression patterns. This novel strategy can be used for predictive reverse engineering combinatorial expression rules from single-cell data and could help identify candidate transcription regulatory processes.

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Type
research article
DOI
10.1371/journal.pone.0034786
Web of Science ID

WOS:000305336600058

PubMed ID

22509357

Author(s)
Khazen, Georges  
Hill, Sean L
Schürmann, Felix  
Markram, Henry  
Date Issued

2012

Publisher

Public Library of Science

Published in
PloS One
Volume

7

Issue

4

Article Number

e34786

Subjects

Gene Expression Regulation

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
GR-FSCH  
BBP-GR-HILL  
LNMC  
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Available on Infoscience
January 28, 2013
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/88260
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