Abstract
Gene expression profiles of postmortem brain tissue represent important resources for understanding neuropsychiatric illnesses. The impact(s) of quality covariables on the analysis and results of gene expression studies are important questions. This paper addressed critical variables which might affect gene expression in two brain regions. Four broad groups of quality indicators in gene expression profiling studies (clinical, tissue, RNA, and microarray quality) were identified. These quality control indicators were significantly correlated, however one quality variable did not account for the total variance in microarray gene expression. The data showed that agonal factors and low pH correlated with decreased integrity of extracted RNA in two brain regions. These three parameters also modulated the significance of alterations in mitochondrial-related genes. The average F-ratio summaries across all transcripts showed that RNA degradation from the AffyRNAdeg program accounted for higher variation than all other quality factors. Taken together, these findings confirmed prior studies, which indicated that quality parameters including RNA integrity, agonal factors, and pH are related to differences in gene expression profiles in postmortem brain. Individual candidate genes can be evaluated with these quality parameters in post hoc analysis to help strengthen the relevance to psychiatric disorders. We find that clinical, tissue, RNA, and microarray quality are all useful variables for collection and consideration in study design, analysis, and interpretation of gene expression results in human postmortem studies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 295-309 |
| Number of pages | 15 |
| Journal | Journal of Neuroscience Methods |
| Volume | 163 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 30 2007 |
Fingerprint
Keywords
- Agonal factors
- Gene expression
- Microarray
- pH
- Postmortem brain tissue
- RNA quality
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Methodological considerations for gene expression profiling of human brain. / Atz, Mary; Walsh, David; Cartagena, Preston; Li, Jun; Evans, Simon; Choudary, Prabhakara V; Overman, Kevin; Stein, Richard; Tomita, Hiro; Potkin, Steven; Myers, Rick; Watson, Stanley J.; Jones, E. G.; Akil, Huda; Bunney, William E.; Vawter, Marquis P.
In: Journal of Neuroscience Methods, Vol. 163, No. 2, 30.07.2007, p. 295-309.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Methodological considerations for gene expression profiling of human brain
AU - Atz, Mary
AU - Walsh, David
AU - Cartagena, Preston
AU - Li, Jun
AU - Evans, Simon
AU - Choudary, Prabhakara V
AU - Overman, Kevin
AU - Stein, Richard
AU - Tomita, Hiro
AU - Potkin, Steven
AU - Myers, Rick
AU - Watson, Stanley J.
AU - Jones, E. G.
AU - Akil, Huda
AU - Bunney, William E.
AU - Vawter, Marquis P.
PY - 2007/7/30
Y1 - 2007/7/30
N2 - Gene expression profiles of postmortem brain tissue represent important resources for understanding neuropsychiatric illnesses. The impact(s) of quality covariables on the analysis and results of gene expression studies are important questions. This paper addressed critical variables which might affect gene expression in two brain regions. Four broad groups of quality indicators in gene expression profiling studies (clinical, tissue, RNA, and microarray quality) were identified. These quality control indicators were significantly correlated, however one quality variable did not account for the total variance in microarray gene expression. The data showed that agonal factors and low pH correlated with decreased integrity of extracted RNA in two brain regions. These three parameters also modulated the significance of alterations in mitochondrial-related genes. The average F-ratio summaries across all transcripts showed that RNA degradation from the AffyRNAdeg program accounted for higher variation than all other quality factors. Taken together, these findings confirmed prior studies, which indicated that quality parameters including RNA integrity, agonal factors, and pH are related to differences in gene expression profiles in postmortem brain. Individual candidate genes can be evaluated with these quality parameters in post hoc analysis to help strengthen the relevance to psychiatric disorders. We find that clinical, tissue, RNA, and microarray quality are all useful variables for collection and consideration in study design, analysis, and interpretation of gene expression results in human postmortem studies.
AB - Gene expression profiles of postmortem brain tissue represent important resources for understanding neuropsychiatric illnesses. The impact(s) of quality covariables on the analysis and results of gene expression studies are important questions. This paper addressed critical variables which might affect gene expression in two brain regions. Four broad groups of quality indicators in gene expression profiling studies (clinical, tissue, RNA, and microarray quality) were identified. These quality control indicators were significantly correlated, however one quality variable did not account for the total variance in microarray gene expression. The data showed that agonal factors and low pH correlated with decreased integrity of extracted RNA in two brain regions. These three parameters also modulated the significance of alterations in mitochondrial-related genes. The average F-ratio summaries across all transcripts showed that RNA degradation from the AffyRNAdeg program accounted for higher variation than all other quality factors. Taken together, these findings confirmed prior studies, which indicated that quality parameters including RNA integrity, agonal factors, and pH are related to differences in gene expression profiles in postmortem brain. Individual candidate genes can be evaluated with these quality parameters in post hoc analysis to help strengthen the relevance to psychiatric disorders. We find that clinical, tissue, RNA, and microarray quality are all useful variables for collection and consideration in study design, analysis, and interpretation of gene expression results in human postmortem studies.
KW - Agonal factors
KW - Gene expression
KW - Microarray
KW - pH
KW - Postmortem brain tissue
KW - RNA quality
UR - http://www.scopus.com/inward/record.url?scp=34249889834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249889834&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2007.03.022
DO - 10.1016/j.jneumeth.2007.03.022
M3 - Article
C2 - 17512057
AN - SCOPUS:34249889834
VL - 163
SP - 295
EP - 309
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
IS - 2
ER -