Recent additions and improvements to the Onto-Tools

Khatri, Purvesh; Sellamuthu, Sivakumar; Malhotra, Pooja; Amin, Kashyap; Done, Arina; Drăghici, Sorin

doi:10.1093/nar/gki472

Cited by 107 publications

(88 citation statements)

References 40 publications

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“…A differential expression cut-off of 1.5-fold was used to filter differentially expressed genes resulting from PDEF expression in the invasive cell lines. Gene ontology classification was performed using Pathway-Express by using the default parameters (Khatri et al, 2005;Draghici et al, 2007;Khatri et al, 2007).…”

Section: Microarray Analysismentioning

confidence: 99%

“…To isolate putative PDEF regulatory target genes that are associated with cell migration, gene ontology associations were examined using Pathway Express (PE) (Khatri et al, 2005;Draghici et al, 2007;Khatri et al, 2007), a freely available web based tool (http://vortex.cs.wayne.edu). PE associates lists of genes with biological interaction pathways and provides an assessment of the impact that those genes have on the pathway of interest.…”

Section: Increased Pdef Expression Impacts Biological Pathways Involvmentioning

confidence: 99%

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Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Turner

Findlay

Kirven

et al. 2008

MBoC

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Prostate derived ETS factor (PDEF) is an ETS (epithelial-specific E26 transforming sequence) family member that has been identified as a potential tumor suppressor. In multiple invasive breast cancer cells, PDEF expression inhibits cell migration by preventing the acquisition of directional morphological polarity conferred by changes in cytoskeleton organization. In this study, microarray analysis was used to identify >200 human genes that displayed a common differential expression pattern in three invasive breast cancer cell lines after expression of exogenous PDEF protein. Gene ontology associations and data mining analysis identified focal adhesion, adherens junctions, cell adhesion, and actin cytoskeleton regulation as cell migration-associated interaction pathways significantly impacted by PDEF expression. Validation experiments confirmed the differential expression of four cytoskeleton-associated genes with known functional associations with these pathways: uPA, uPAR, LASP1, and VASP. Significantly, chromatin immunoprecipitation studies identified PDEF as a direct negative regulator of the metastasis-associated gene uPA and phenotypic rescue experiments demonstrate that exogenous urokinase plasminogen activator (uPA) expression can restore the migratory ability of invasive breast cancer cells expressing PDEF. Furthermore, immunofluorescence studies identify the subcellular relocalization of urokinase plasminogen activator receptor (uPAR), LIM and SH3 protein (LASP1), and vasodilatorstimulated protein (VASP) as a possible mechanism accounting for the loss of morphological polarity observed upon PDEF expression.

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Section: Microarray Analysismentioning

confidence: 99%

Section: Increased Pdef Expression Impacts Biological Pathways Involvmentioning

confidence: 99%

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Turner

Findlay

Kirven

et al. 2008

MBoC

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“…Figure 7 illustrates the remarkable effect of hLsm1 overexpression on the expression profile of MCF10LacZ cells, as well as the striking similarity of the profiles of MCF10Lsm1 and SUM44 cells. All subsequent bioinformatics analyses were performed using this subset of genes with the Onto-Express (OE) and Pathway-Express (PE) programs (Khatri et al, 2002(Khatri et al, , 2004(Khatri et al, , 2005Draghici et al, 2003aDraghici et al, , b, 2006. OE uses annotation data to construct functional profiles for different biological conditions and provides P-values to distinguish between significant biological effects and random events (Khatri et al, 2005;Draghici, 2003c).…”

Section: Hlsm1 Transforms Mammary Epithelial Cellsmentioning

confidence: 99%

“…All subsequent bioinformatics analyses were performed using this subset of genes with the Onto-Express (OE) and Pathway-Express (PE) programs (Khatri et al, 2002(Khatri et al, , 2004(Khatri et al, , 2005Draghici et al, 2003aDraghici et al, , b, 2006. OE uses annotation data to construct functional profiles for different biological conditions and provides P-values to distinguish between significant biological effects and random events (Khatri et al, 2005;Draghici, 2003c). Figure 8a shows the molecular functions of genes altered in both MCF10Lsm1 and SUM44 cells compared to MCF10LacZ cells, with the most common function being transcription factor activity.…”

Section: Hlsm1 Transforms Mammary Epithelial Cellsmentioning

confidence: 99%

“…We used the PE algorithm to assess the impact of hLsm1 overexpression in both MCF10Lsm1 and SUM44 cells on various functional pathways that may be important for cancer progression and transformation (Khatri et al, 2005;Draghici, 2003c). The impact factor measures, in a statistically robust fashion, the pathways most affected by changes in gene expression by considering the proportion of differentially regulated genes, perturbation factors of all pathway genes, as well as the propagation of these perturbations throughout the pathway.…”

Section: Hlsm1 Transforms Mammary Epithelial Cellsmentioning

confidence: 99%

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Transforming function of the LSM1 oncogene in human breast cancers with the 8p11–12 amplicon

et al. 2006

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Amplification of the 8p11-12 region occurs in 15-20% of breast cancers, but the driving oncogene at this locus has yet to be definitively identified. We mapped the 8p11-12 amplicon in breast cancer cell lines and primary human breast cancers and identified the candidate oncogene human Sm-like protein (hLsm1, LSM1) based on increases in copy number and expression level relative to human mammary epithelial cells. To examine the oncogenic role of LSM1, we overexpressed this gene in MCF10A mammary epithelial cells and inhibited its production in the SUM44 breast cancer cell line, which has a natural amplification and overexpression of LSM1. Our data confirmed that LSM1 is an oncogene from the 8p11-12 amplicon by showing that hLsm1 overexpression induced growth factor-independent proliferation and soft agar colony formation in MCF10A cells, and hLsm1 inhibition in SUM44 cells dramatically reduced soft agar growth. Little is known about hLsm1 function other than its involvement in mRNA degradation; therefore, we used expression microarray analysis to investigate how hLsm1 affects cell transformation in MCF10A and SUM44 cells. We identified numerous genes altered following hLsm1 overexpression common to SUM44 breast cancer cells that play important roles in cell cycle regulation, cell proliferation and other cancer-promoting processes. Future work will continue to characterize these important changes to achieve a more complete understanding of the mechanism of hLsm1's effect on cancer progression.

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Bioinformatics for High‐Throughput Toxico‐Epigenomics Studies

Sartor

Dolinoy

Rozek

et al. 2012

Toxicology and Epigenetics

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Recent additions and improvements to the Onto-Tools

Abstract: The Onto-Tools suite is composed of an annotation database and six seamlessly integrated,

Cited by 107 publications

References 40 publications

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Transforming function of the LSM1 oncogene in human breast cancers with the 8p11–12 amplicon

Bioinformatics for High‐Throughput Toxico‐Epigenomics Studies

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