GobyWeb: Simplified Management and Analysis of Gene Expression and DNA Methylation Sequencing Data

Dorff, Kevin C.; Chambwe, Nyasha; Zeno, Zachary; Simi, Maria; Shaknovich, Rita; Campagne, Fabien

doi:10.1371/journal.pone.0069666

Cited by 30 publications

(36 citation statements)

References 29 publications

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“…This approach provides a global view of alterations to the transcriptome due to manipulation of miR-7 with the expectation that miR-7 target genes released from regulation by miR-7 sponge will be upregulated. Total RNA was isolated from E12.5 dorsal cortices of three 7-sp and three wild-type littermate embryos, sequenced and analyzed using GobyWeb (Dorff et al, 2013). Overall gene expression was not greatly different from wild-type with only a few genes exhibiting large deviations from controls (Figure 6B).…”

Section: Resultsmentioning

confidence: 99%

Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

et al. 2014

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Summary Proper growth of the mammalian cerebral cortex is crucial for normal brain functions and is controlled by precise gene expression regulation. We here have identified miRNA miR-7 that is highly expressed in cortical neural progenitors, and generated miR-7 sponge transgenic mice in which miR-7 silencing activity is specifically knocked down in the embryonic cortex. Blocking miR-7 function causes microcephaly-like brain defects due to reduced intermediate progenitor (IP) production and apoptosis. Upregulation of miR-7 target genes, including those implicated in the p53 pathway such as Ak1 and Cdkn1a (p21), are responsible for abnormalities in neural progenitors. Furthermore, ectopic expression of Ak1 or p21, and specific blockade of miR-7 binding sites in target genes using protectors in vivo are able to recreate reduced IP production. Using conditional miRNA sponge transgenic approaches, we have uncovered an unexpected role for miR-7 in cortical growth through its interactions with genes in the p53 pathway.

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Section: Resultsmentioning

confidence: 99%

Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

et al. 2014

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“…Reads were uploaded to the GobyWeb system64 and aligned to the 1000 genome human reference sequence65 with the STAR aligner66. Ensembl annotations for transcripts were obtained from Biomart and Ensembl automatically using GobyWeb.…”

Section: Methodsmentioning

confidence: 99%

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Ruíz

Zhao

Chandakkar

et al. 2016

Sci Rep

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Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation. Here, we investigated whether the transmammary delivery route could improve the ease and consistency of administering anti-BMP9/10 antibodies in the postnatal retinal angiogenesis model. We found that anti-BMP9/10 antibodies, when intraperitoneally injected into lactating dams, are efficiently transferred into the blood circulation of lactationally-exposed neonatal pups. Strikingly, pups receiving anti-BMP9/10 antibodies via lactation displayed consistent and robust vascular pathology in the retina, which included hypervascularization and defects in arteriovenous specification, as well as the presence of multiple and massive arteriovenous malformations. Furthermore, RNA-Seq analyses of neonatal retinas identified an increase in the key pro-angiogenic factor, angiopoietin-2, as the most significant change in gene expression triggered by the transmammary delivery of anti-BMP9/10 antibodies. Transmammary-delivered BMP9/10 immunoblocking in the mouse neonatal retina is therefore a practical, noninvasive, reliable, and robust model of HHT vascular pathology.

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“…Sequencing data were uploaded into the GobyWeb application (Campagne lab) for alignment to the genome. Differential expression analysis was performed initially using GobyWeb [26]. Differential expression analysis was repeated using EdgeR, an RNAseq analysis package already cited in published reports [27–29].…”

Section: Methodsmentioning

confidence: 99%

Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

Marcinkiewicz

Gudas

2014

Experimental Cell Research

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To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes.

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GobyWeb: Simplified Management and Analysis of Gene Expression and DNA Methylation Sequencing Data

Cited by 30 publications

References 29 publications

Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

Growth of the Developing Cerebral Cortex Is Controlled by MicroRNA-7 through the p53 Pathway

A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10

Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

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