Biomedical subjects

Dabao Zhang

Publications and source records attributed to Dabao Zhang.

5 recordsLinked to original sources

PubMed2006

Multiplicative background correction for spotted microarrays to improve reproducibility.

We propose a simple approach, the multiplicative background correction, to solve a perplexing problem in spotted microarray data analysis: correcting the foreground intensities for the background noise, especially for spots with genes that are weakly expressed or not at all. The conventional approach, the additive background correction, directly subtracts the background intensities from foreground intensities. When the foreground intensities marginally dominate the background intensities, the additive background correction provides unreliable estimates of the differential gene expression levels and usually presents M-A plots with fishtails or fans. Unreliable additive background correction makes it preferable to ignore the background noise, which may increase the number of false positives. Based on the more realistic multiplicative assumption instead of the conventional additive assumption, we propose to logarithmically transform the intensity readings before the background correction, with the logarithmic transformation symmetrizing the skewed intensity readings. This approach not only precludes the fishtails and fans in the M-A plots, but provides highly reproducible background-corrected intensities for both strongly and weakly expressed genes. The superiority of the multiplicative background correction to the additive one as well as the no background correction is justified by publicly available self-hybridization datasets.

Arabidopsis↗

PubMed2005

HIV-1 transactivator of transcription protein induces mitochondrial hyperpolarization and synaptic stress leading to apoptosis.

Despite the efficacy of highly active antiretroviral therapy in reducing viral burden, neurologic disease associated with HIV-1 infection of the CNS has not decreased in prevalence. HIV-1 does not induce disease by direct infection of neurons, although extensive data suggest that intra-CNS viral burden correlates with both the severity of virally induced neurologic disease, and with the generation of neurotoxic metabolites. Many of these molecules are capable of inducing neuronal apoptosis in vitro, but neuronal apoptosis in vivo does not correlate with CNS dysfunction, thus prompting us to investigate cellular and synaptic events occurring before cell death that may contribute to HIV-1-associated neurologic disease. We now report that the HIV-1 regulatory protein transactivator of transcription protein (Tat) increased oxidative stress, ATP levels, and mitochondrial membrane potential in primary rodent cortical neurons. Additionally, a proinflammatory cellular metabolite up-regulated by Tat, platelet-activating factor, also induced oxidative stress and mitochondrial hyperpolarization in neurons, suggesting that this type of metabolic dysfunction may occur on a chronic basis during HIV-1 infection of the CNS. Tat-induced mitochondrial hyperpolarization could be blocked with a low dose of the protonophore FCCP, or the mitochondrial KATP channel antagonist, tolbutamide. Importantly, blocking the mitochondrial hyperpolarization attenuated Tat-induced neuronal apoptosis, suggesting that increased mitochondrial membrane potential may be a causal event in precipitating neuronal apoptosis in cell culture. Finally, Tat and platelet-activating factor also increased neuronal vesicular release, which may be related to increased mitochondrial bioenergetics and serve as a biomarker for early damage to neurons.

Adenosine Triphosphate↗

PubMed2005

Bayesian normalization and identification for differential gene expression data.

Commonly accepted intensity-dependent normalization in spotted microarray studies takes account of measurement errors in the differential expression ratio but ignores measurement errors in the total intensity, although the definitions imply the same measurement error components are involved in both statistics. Furthermore, identification of differentially expressed genes is usually considered separately following normalization, which is statistically problematic. By incorporating the measurement errors in both total intensities and differential expression ratios, we propose a measurement-error model for intensity-dependent normalization and identification of differentially expressed genes. This model is also flexible enough to incorporate intra-array and inter-array effects. A Bayesian framework is proposed for the analysis of the proposed measurement-error model to avoid the potential risk of using the common two-step procedure. We also propose a Bayesian identification of differentially expressed genes to control the false discovery rate instead of the ad hoc thresholding of the posterior odds ratio. The simulation study and an application to real microarray data demonstrate promising results.

Bayes Theorem↗

PubMed2005

Orphanin FQ antagonizes the inhibition of Ca(2+) currents induced by mu-opioid receptors.

Orphanin FQ (OFQ), an endogenous peptide ligand of opioid receptor-like receptors (ORLs), has properties similar to traditional opioids. This peptide inhibits adenylyl cyclase and voltage-gated calcium channels but stimulates inwardly rectifying potassium channels. Among other actions, however, OFQ also has pharmacological functions that are different from, or even opposite to, those of opioids. For example, OFQ antagonizes the behavioral analgesic effects mediated by kappa- and mu-opioid receptors. In a previous paper, we reported that OFQ antagonizes inhibition of calcium channels mediated by kappa-opioid receptors. We report here that OFQ also antagonizes the inhibition of calcium channels mediated by mu-opioid receptor. Further, single-cell RT-PCR reveals that the antagonistic effect of OFQ is correlated with the presence of ORL1 mRNA in individual cells.

Analgesics↗

PubMed2004

Mapping multiple Quantitative Trait Loci by Bayesian classification.

We developed a classification approach to multiple quantitative trait loci (QTL) mapping built upon a Bayesian framework that incorporates the important prior information that most genotypic markers are not cotransmitted with a QTL or their QTL effects are negligible. The genetic effect of each marker is modeled using a three-component mixture prior with a class for markers having negligible effects and separate classes for markers having positive or negative effects on the trait. The posterior probability of a marker's classification provides a natural statistic for evaluating credibility of identified QTL. This approach performs well, especially with a large number of markers but a relatively small sample size. A heat map to visualize the results is proposed so as to allow investigators to be more or less conservative when identifying QTL. We validated the method using a well-characterized data set for barley heading values from the North American Barley Genome Mapping Project. Application of the method to a new data set revealed sex-specific QTL underlying differences in glucose-6-phosphate dehydrogenase enzyme activity between two Drosophila species. A simulation study demonstrated the power of this approach across levels of trait heritability and when marker data were sparse.

Animals↗