A method for detection of differential gene expression in the presence of inter-individual variability in response

Rocke, David M.; Goldberg, Zelanna; Schweitert, Chad; Santana, Alison

doi:10.1093/bioinformatics/bti667

Cited by 16 publications

(16 citation statements)

References 4 publications

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“…Matched voxels from the different effort and same effort conditions were compared using the paired t test, and p-values were corrected for multiple comparisons using the Benjamini-Hochberg control of false discovery rate (Benjamini and Hochberg, 1995). However, as in previous PET studies with low degrees of freedom (Nichols and Hayasaka, 2003;Rocke et al, 2005), all individual voxel comparisons missed significance if using the false discovery rate procedure. As proposed by Genovese et al (2002), we therefore set a threshold of p ϭ 0.01 (corresponding to t ϭ 3.48, df ϭ 7) for uncorrected p-values.…”

Section: Experiments 1: Effort-based Decision Makingmentioning

confidence: 64%

Effort-Based Decision Making in the rat: An [18F]Fluorodeoxyglucose Micro Positron Emission Tomography Study

Endepols

Sommer

Backes

et al. 2010

Journal of Neuroscience

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Decision making refers to the process by which subjects choose between competing courses of action based on the expected costs and benefits of their consequences. Lesion studies in rats suggest that the anterior cingulate cortex and the nucleus accumbens are key structures of a neural system that subserves effort-based decision making. Little is known about brain activation associated with effortbased decisions in intact rats. Using an open hypothesis approach, we used 2-deoxy-2[ 18 F]fluoro-D-glucose positron emission tomography (FDG-PET) to assess regional metabolic changes in two conditions of an effort-based decision making task. In the "same effort" condition, male rats could choose between two response options associated with the same effort but different reward sizes, i.e., decision making was simply a function of reward size. By contrast, in the "different effort" condition, an integration of different efforts and reward sizes associated with the two response options was necessary before making a decision. Separate PET scans were performed from each condition. Subtractive analysis revealed that metabolic activity was increased in the different effort relative to the same effort condition in the left anterior cingulate, left orbitofrontal and prelimbic cortex region. Metabolic activity was decreased in the infralimbic cortex and septum region. Our findings suggest that making decisions on how much effort to invest to obtain greater rewards evokes changes of metabolic activity in multiple brain areas associated with cognitive, limbic, motor and autonomic functions. This study demonstrates that FDG-PET provides a tool to determine in rats regional brain metabolic activity in cognitive tasks.

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Section: Experiments 1: Effort-based Decision Makingmentioning

confidence: 64%

Effort-Based Decision Making in the rat: An [18F]Fluorodeoxyglucose Micro Positron Emission Tomography Study

Endepols

Sommer

Backes

et al. 2010

Journal of Neuroscience

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“…If transcripts were up-regulated or down-regulated at 3 and 8 hours compared with 0 and 24 hours, we detected a transient response that returns to baseline by 24 hours. The method of Rocke et al (20) was chosen because of the small number of data points per patient, as well as previously observed variability in radiation response between individuals. This method is designed to detect differentially expressed gene groups and pathways based on the responses of multiple probe sets corresponding to the gene group or pathway.…”

Section: Resultsmentioning

confidence: 99%

“…When none of the resample-based statistics exceeded the actual statistic, the p value was given as p < 0.001, which is the most significant result possible with this method. Details are given in Rocke et al (20). It should be noted that another way to evaluate significance empirically is to permute the arrays.…”

Section: Resultsmentioning

confidence: 99%

“…Full details are given in reports by Rocke and colleagues (19,20). To summarize, for each probe set and individual patient, a t test was conducted to determine the difference between the 3-and 8-hour measurements versus the 0-and 24-hour measurements.…”

Section: Discussionmentioning

confidence: 99%

“…We have developed a model for direct evaluation of the effects of LDIR in normal, healthy human tissue. Initial studies using this approach in conjunction with a statistically valid data analysis model have been used to evaluate the dose response profile at 3 hours postexposure (18)(19)(20). The studies presented herein describe the human responses to equal doses of LDIR over a 24-hour period following a single radiation exposure.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transient Genome-Wide Transcriptional Response to Low-Dose Ionizing Radiation In Vivo in Humans

Berglund

Rocke

Dai

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose-The in vivo effects of low-dose low linear energy transfer ionizing radiation on healthy human skin are largely unknown. Using a patient-based tissue acquisition protocol, we have performed a series of genomic analyses on the temporal dynamics over a 24-hour period to determine the radiation response after a single exposure of 10 cGy.Methods and Materials-RNA from each patient tissue sample was hybridized to an Affymetrix Human Genome U133 Plus 2.0 array. Data analysis was performed on selected gene groups and pathways.Results-Nineteen gene groups and seven gene pathways that had been shown to be radiation responsive were analyzed. Of these, nine gene groups showed significant transient transcriptional changes in the human tissue samples, which returned to baseline by 24 hours postexposure.Conclusions-Low doses of ionizing radiation on full-thickness human skin produce a definable temporal response out to 24 hours postexposure. Genes involved in DNA and tissue remodeling, cell cycle transition, and inflammation show statistically significant changes in expression, despite variability between patients. These data serve as a reference for the temporal dynamics of ionizing radiation response following low-dose exposure in healthy full-thickness human skin.

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What Have “Omics” Taught Us about the Health Risks Associated with Exposure to Low Doses of Ionizing Radiation

Morgan

Sowa

2011

Cancer Risk Evaluation

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A method for detection of differential gene expression in the presence of inter-individual variability in response

Abstract: Software in the form of R code to perform the required test is available from the first author or from his website http://www.idav.ucdavis.edu/~dmrocke/software; however the procedures are also easily performed using any standard statistical software.

Cited by 16 publications

References 4 publications

Effort-Based Decision Making in the rat: An [18F]Fluorodeoxyglucose Micro Positron Emission Tomography Study

Effort-Based Decision Making in the rat: An [18F]Fluorodeoxyglucose Micro Positron Emission Tomography Study

Transient Genome-Wide Transcriptional Response to Low-Dose Ionizing Radiation In Vivo in Humans

What Have “Omics” Taught Us about the Health Risks Associated with Exposure to Low Doses of Ionizing Radiation

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