Leveraging two-way probe-level block design for identifying differential gene expression with high-density oligonucleotide arrays

Barrera, Leah O.; Benner, Chris; Tao, Yong-Chuan; Winzeler, Elizabeth A.; Zhou, Yingyao

doi:10.1186/1471-2105-5-42

Cited by 24 publications

(3 citation statements)

References 18 publications

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“…GC-RMA was used for probe-level normalization of array intensities (126). Batch effects caused by multiple data sources were corrected using ComBat (127). Probes from each probe set with the greatest interquartile range were retained for gene expression analysis.…”

Section: Methodsmentioning

confidence: 99%

Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

et al. 2014

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, KRAS has thus far not been a viable therapeutic target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), a protein regulated by the Hippo pathway during tissue development and homeostasis, was increased in human PDAC tissue compared with that in normal pancreatic epithelia. In genetically engineered KrasG12D and KrasG12D: Trp53R172H mouse models, pancreas-specific deletion of Yap halted the progression of early neoplastic lesions to PDAC without affecting normal pancreatic development and endocrine function. Although Yap was dispensable for acinar to ductal metaplasia (ADM), an initial step in the progression to PDAC, Yap was critically required for the proliferation of mutant Kras or Kras:Trp53 neoplastic pancreatic ductal cells in culture and for their growth and progression to invasive PDAC in mice. Yap functioned as a critical transcriptional switch downstream of the oncogenic KRAS–mitogen-activated protein kinase (MAPK) pathway, promoting the expression of genes encoding secretory factors that cumulatively sustained neoplastic proliferation, a tumorigenic stromal response in the tumor microenvironment, and PDAC progression in Kras and Kras: Trp53 mutant pancreas tissue. Together, our findings identified Yap as a critical oncogenic KRAS effector and a promising therapeutic target for PDAC and possibly other types of KRAS-mutant cancers.

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Section: Methodsmentioning

confidence: 99%

Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

et al. 2014

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“…heterogeneous variances are modeled) on the ranks of each sample using a family-wise false discovery rate of 5% [ 93 ]. These analyses are similar to the non-parametric Friedman and Mack-Skillings rank tests used for the analysis of microarray data [ 94 - 97 ]. This approach is more conservative than the pooled t -test analysis of rank data advocated by Conover [ 98 ] since the Welch t -test models the obvious heteroscedastic variability between the ranks of the drip flow biofilm transcriptome and the ranks of the comparator transcriptomes.…”

Section: Methodsmentioning

confidence: 99%

Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis

Folsom¹,

Richards

Pitts³

et al. 2010

BMC Microbiol

122

117

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BackgroundTranscriptome analysis was applied to characterize the physiological activities of Pseudomonas aeruginosa grown for three days in drip-flow biofilm reactors. Conventional applications of transcriptional profiling often compare two paired data sets that differ in a single experimentally controlled variable. In contrast this study obtained the transcriptome of a single biofilm state, ranked transcript signals to make the priorities of the population manifest, and compared ranki ngs for a priori identified physiological marker genes between the biofilm and published data sets.ResultsBiofilms tolerated exposure to antibiotics, harbored steep oxygen concentration gradients, and exhibited stratified and heterogeneous spatial patterns of protein synthetic activity. Transcriptional profiling was performed and the signal intensity of each transcript was ranked to gain insight into the physiological state of the biofilm population. Similar rankings were obtained from data sets published in the GEO database http://www.ncbi.nlm.nih.gov/geo. By comparing the rank of genes selected as markers for particular physiological activities between the biofilm and comparator data sets, it was possible to infer qualitative features of the physiological state of the biofilm bacteria. These biofilms appeared, from their transcriptome, to be glucose nourished, iron replete, oxygen limited, and growing slowly or exhibiting stationary phase character. Genes associated with elaboration of type IV pili were strongly expressed in the biofilm. The biofilm population did not indicate oxidative stress, homoserine lactone mediated quorum sensing, or activation of efflux pumps. Using correlations with transcript ranks, the average specific growth rate of biofilm cells was estimated to be 0.08 h-1.ConclusionsCollectively these data underscore the oxygen-limited, slow-growing nature of the biofilm population and are consistent with antimicrobial tolerance due to low metabolic activity.

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“…All gene expression values were subjected to a probe-level two-way ANOVA test to determine variability of expression across all samples [13] . A total of 4,326 genes were identified as differentially expressed with p ANOVA <0.05 and FC >2 ( Table S1 ) and were subjected to further OPI clustering analysis.…”

Section: Methodsmentioning

confidence: 99%

A Systems-Based Analysis of Plasmodium vivax Lifecycle Transcription from Human to Mosquito

et al. 2010

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BackgroundUp to 40% of the world's population is at risk for Plasmodium vivax malaria, a disease that imposes a major public health and economic burden on endemic countries. Because P. vivax produces latent liver forms, eradication of P. vivax malaria is more challenging than it is for P. falciparum. Genetic analysis of P. vivax is exceptionally difficult due to limitations of in vitro culture. To overcome the barriers to traditional molecular biology in P. vivax, we examined parasite transcriptional changes in samples from infected patients and mosquitoes in order to characterize gene function, define regulatory sequences and reveal new potential vaccine candidate genes.Principal FindingsWe observed dramatic changes in transcript levels for various genes at different lifecycle stages, indicating that development is partially regulated through modulation of mRNA levels. Our data show that genes involved in common biological processes or molecular machinery are co-expressed. We identified DNA sequence motifs upstream of co-expressed genes that are conserved across Plasmodium species that are likely binding sites of proteins that regulate stage-specific transcription. Despite their capacity to form hypnozoites we found that P. vivax sporozoites show stage-specific expression of the same genes needed for hepatocyte invasion and liver stage development in other Plasmodium species. We show that many of the predicted exported proteins and members of multigene families show highly coordinated transcription as well.ConclusionsWe conclude that high-quality gene expression data can be readily obtained directly from patient samples and that many of the same uncharacterized genes that are upregulated in different P. vivax lifecycle stages are also upregulated in similar stages in other Plasmodium species. We also provide numerous examples of how systems biology is a powerful method for determining the likely function of genes in pathogens that are neglected due to experimental intractability.

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Leveraging two-way probe-level block design for identifying differential gene expression with high-density oligonucleotide arrays

Cited by 24 publications

References 18 publications

Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis

A Systems-Based Analysis of Plasmodium vivax Lifecycle Transcription from Human to Mosquito

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