A look behind the curtain: Epilepsy microarray consortium

Jennifer A. Kearney*

*Corresponding author for this work

Research output: Contribution to journalComment/debate

Abstract

Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling. In each epilepsy model, RNA was harvested from laser-captured dentate granule cells from six rats at four time points early in the process of developing epilepsy, and data were collected from two independent laboratories in each rodent model except SSSE. Hierarchical clustering of differentially-expressed transcripts in the three SE models revealed complete separation between controls and SE rats isolated 1 day after SE. However, concordance of gene expression changes in the SE models was only 26-38% between laboratories, and 4.5% among models, validating the consortium approach. Transcripts with unusually highly variable control expression across laboratories provide a 'red herring' list for low-powered studies.

Original languageEnglish (US)
Pages (from-to)374-376
Number of pages3
JournalEpilepsy Currents
Volume17
Issue number6
DOIs
StatePublished - Jan 1 2017

Fingerprint

Status Epilepticus
Epilepsy
Pilocarpine
Kainic Acid
Amygdala
Nervous System
Cluster Analysis
Psychiatry
Rodentia
Lasers
Animal Models
RNA
Gene Expression
Genes

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{0130274ad7714469b60281ae277b066d,
title = "A look behind the curtain: Epilepsy microarray consortium",
abstract = "Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling. In each epilepsy model, RNA was harvested from laser-captured dentate granule cells from six rats at four time points early in the process of developing epilepsy, and data were collected from two independent laboratories in each rodent model except SSSE. Hierarchical clustering of differentially-expressed transcripts in the three SE models revealed complete separation between controls and SE rats isolated 1 day after SE. However, concordance of gene expression changes in the SE models was only 26-38{\%} between laboratories, and 4.5{\%} among models, validating the consortium approach. Transcripts with unusually highly variable control expression across laboratories provide a 'red herring' list for low-powered studies.",
author = "Kearney, {Jennifer A.}",
year = "2017",
month = "1",
day = "1",
doi = "10.5698/1535-7597.17.6.374",
language = "English (US)",
volume = "17",
pages = "374--376",
journal = "Epilepsy Currents",
issn = "1535-7597",
publisher = "American Epilepsy Society",
number = "6",

}

A look behind the curtain : Epilepsy microarray consortium. / Kearney, Jennifer A.

In: Epilepsy Currents, Vol. 17, No. 6, 01.01.2017, p. 374-376.

Research output: Contribution to journalComment/debate

TY - JOUR

T1 - A look behind the curtain

T2 - Epilepsy microarray consortium

AU - Kearney, Jennifer A.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling. In each epilepsy model, RNA was harvested from laser-captured dentate granule cells from six rats at four time points early in the process of developing epilepsy, and data were collected from two independent laboratories in each rodent model except SSSE. Hierarchical clustering of differentially-expressed transcripts in the three SE models revealed complete separation between controls and SE rats isolated 1 day after SE. However, concordance of gene expression changes in the SE models was only 26-38% between laboratories, and 4.5% among models, validating the consortium approach. Transcripts with unusually highly variable control expression across laboratories provide a 'red herring' list for low-powered studies.

AB - Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling. In each epilepsy model, RNA was harvested from laser-captured dentate granule cells from six rats at four time points early in the process of developing epilepsy, and data were collected from two independent laboratories in each rodent model except SSSE. Hierarchical clustering of differentially-expressed transcripts in the three SE models revealed complete separation between controls and SE rats isolated 1 day after SE. However, concordance of gene expression changes in the SE models was only 26-38% between laboratories, and 4.5% among models, validating the consortium approach. Transcripts with unusually highly variable control expression across laboratories provide a 'red herring' list for low-powered studies.

UR - http://www.scopus.com/inward/record.url?scp=85034825589&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034825589&partnerID=8YFLogxK

U2 - 10.5698/1535-7597.17.6.374

DO - 10.5698/1535-7597.17.6.374

M3 - Comment/debate

C2 - 29217985

AN - SCOPUS:85034825589

VL - 17

SP - 374

EP - 376

JO - Epilepsy Currents

JF - Epilepsy Currents

SN - 1535-7597

IS - 6

ER -