Quality control for microarray analysis of human brain samples: The impact of postmortem factors, RNA characteristics, and histopathology

Shared Gene Expression Alterations in Schizophrenia and Bipolar Disorder

“…Microarrays are sensitive to the effect of agonalpH differences in samples. The SMRI Microarray cases have a significantly reduced pH compared with control subjects, although most cases are rapid deaths (49). This latter observation might indicate that pH is part of the pathology in BPD and SZ.…”

Mitochondrial involvement in psychiatric disorders

“…A more difficult question to address technically is whether differences in mitochondria physiology associated with agonal-pH differences influence the same genes implicated with psychiatric disorders. Recently, Weis et al (2007) (69) demonstrated that pH was decreased in BPD (n = 113) and SZ (n = 120) postmortem brain tissue compared to controls (n = 120). This interesting study also compared control subjects with obvious histopathological abnormalities and cerebellar granular cell layer necrosis (CGLN) to controls subjects without CGLN and found decreased pH of 0.4 in CGLN+ group.…”

“…The Weis et al 2007 (69) study did not rule out a relationship of agonal factors to pH which could have influenced the group differences. Linear regression models would be useful to predict pH using the data available at the Stanley Foundation-557 collection (69) to determine the strongest predictors of pH. Beyond the usual predictors of age, PMI, agonal factors and tissue necrosis, it would be interesting to see if the lifetime fluphenazine daily equivalents, smoking, and other variables such as mtDNA SNPs (see below) were strongly predictive.…”

“…One method is to develop animal and cellular models that have profiles similar to BPD and SZ gene expression profiles and to show that the pathophysiology involves mitochondrial-related gene expression. The other method is to perform rigorously controlled studies of covariates and gene expression (62,69,(79)(80)(81) which we further comment upon below.…”

Prediction of qualitative outcome of oligonucleotide microarray hybridization by measurement of RNA integrity using the 2100 Bioanalyzer™ capillary electrophoresis system

“…Different values have reportedly been used as a threshold for poor-quality assays. Finkelstein et al used 25% as a threshold for outliers, a value which is also recommended by the Tumor Analysis Best Practices Working Group [6], whereas Weis et al [7] found a value below 35% to correlate with poor-quality assays in their experiments. 2.…”