Pathway studio—the analysis and navigation of molecular networks

Nikitin, Alexander P.; Egorov, Sergei; Daraselia, Nikolai; Mazo, Ilya

doi:10.1093/bioinformatics/btg290

Cited by 614 publications

(496 citation statements)

References 2 publications

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“…35 A DEP interaction network was generated with Pathway Studio version 5.0 (Ariadne Genomis, Rockville, MD) and the Resnet 5 database. 36 Common downstream targets or upstream regulators of multiple proteins were identified using this software, which facilitated the process of selecting key factors and potential mechanisms from the large number of proteins.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Zhang

Tao

et al. 2010

J. Proteome Res.

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Tumor reversion is defined as the process by which cancer cells lose their malignant phenotype. However, relatively little is known about the cellular proteome changes that occur during the reversion process. A biological model of multiple myeloma (MM) reversion was established by using the H-1 parvovirus as a tool to select for revertant cells from MM cells. Isolated revertant cells displayed a strongly suppressed malignant phenotype both in vitro and in vivo. To explore possible mechanisms of MM reversion, the protein profiles of the revertant and parental MM cells were compared using a quantitative proteomic strategy termed SILAC-MS. Our results revealed that 379 proteins were either activated or inhibited during the reversion process, with a much greater proportion of the proteins, including STAT3, TCTP, CDC2, BAG2, and PCNA, being inhibited. Of these, STAT3, which is significantly down regulated, was selected for further functional studies. Inhibition of STAT3 expression by RNA interference resulted in suppression of the malignant phenotype and concomitant down regulation of TCTP expression, suggesting that myeloma reversion operates, at least in part, through inhibition of STAT3. Our results provide novel insights into the mechanisms of tumor reversion and suggest new alternative approaches for MM treatment.

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Section: Methodsmentioning

confidence: 99%

Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Zhang

Tao

et al. 2010

J. Proteome Res.

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“…A Q-value, representative of the FDR<0.05 and p<0.05 were the basis for statistical significance from this analysis. Finally, gene networks were prepared with Pathway Studio® 4.0 software (Ariadne Genomics, Rockville, MD) (Nikitin et al, 2003). The software uses Medscan natural language processing to gather information from all abstracts on PubMed and other public data sources, which is extracted to assemble molecular networks.…”

Section: Functional Analysis Of Significant Genesmentioning

confidence: 99%

Time course investigation of PPARα- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression

Woods

Kosyk

Bradford

et al. 2007

Toxicology and Applied Pharmacology

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Administration of peroxisome proliferators to rodents causes proliferation of peroxisomes, induction of β-oxidation enzymes, hepatocelluar hypertrophy and hyperplasia, with chronic exposure ultimately leading to hepatocellular carcinomas. Many responses associated with peroxisome proliferators are nuclear receptor-mediated events involving peroxisome proliferators-activated receptor alpha (PPARα). A role for nuclear receptor-independent events has also been shown, with evidence of Kupffer cell-mediated free radical production, presumably through NAPDH oxidase, induction of redox-sensitive transcription factors involved in cytokine production and cytokinemediated cell replication following acute treatment with peroxisome proliferators in rodents. Recent studies have demonstrated, by using p47 phox -null mice which are deficient in NADPH oxidase, that this enzyme is not related to the phenotypic events caused by prolonged administration of peroxisome proliferators. In an effort to determine the timing of the transition from Kupffer cell-to PPARα-dependent modulation of peroxisome proliferator effects, gene expression was assessed in liver from Pparα-null, p47 phox -null and corresponding wild-type mice following treatment with 4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid (WY-14,643) for 8 h, 24 h, 72 h, 1 wk, or 4 wks. WY-14,643-induced gene expression in p47 phox -null mouse liver differed substantially from wildtype mice at acute doses and striking differences in baseline expression of immune related genes were evident. Pathway mapping of genes that respond to WY-14,643 in a time-and dose-dependent manner demonstrates suppression of immune response, cell death and signal transduction and promotion of lipid metabolism, cell cycle and DNA repair. Furthermore, these pathways were largely dependent on PPARα, not NADPH oxidase demonstrating a temporal shift in response to peroxisome proliferators. Overall, this study shows that NADPH oxidase-dependent events, while detectable following acute treatment, are transient and short-lived. To the contrary, a strong PPARα-specific gene signature was evident in mice that were continually exposed to WY-14,643.

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“…The identified regulatory components were networked using Pathway Studio software version 9 based on Fisher test with p-values≤0.01 (Nikitin et al 2003;Subramanian et al 2005). The database of software could provide a number of relevant components, which were not identified among the differentially expressed genes, to make the regulatory network more complete.…”

Section: Identification Of Drought-responsive Regulatory Componentsmentioning

confidence: 99%

Mining expressed sequence tags of rapeseed (Brassica napus L.) to predict the drought responsive regulatory network

Shamloo‐Dashtpagerdi

Razi

Ebrahimie

2015

Physiol Mol Biol Plants

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It is of great significance to understand the regulatory mechanisms by which plants deal with drought stress. Two EST libraries derived from rapeseed (Brassica napus) leaves in non-stressed and drought stress conditions were analyzed in order to obtain the transcriptomic landscape of drought-exposed B. napus plants, and also to identify and characterize significant drought responsive regulatory genes and microRNAs. The functional ontology analysis revealed a substantial shift in the B. napus transcriptome to govern cellular drought responsiveness via different stress-activated mechanisms. The activity of transcription factor and protein kinase modules generally increased in response to drought stress. The 26 regulatory genes consisting of 17 transcription factor genes, eight protein kinase genes and one protein phosphatase gene were identified showing significant alterations in their expressions in response to drought stress. We also found the six microRNAs which were differentially expressed during drought stress supporting the involvement of a posttranscriptional level of regulation for B. napus drought response. The drought responsive regulatory network shed light on the significance of some regulatory components involved in biosynthesis and signaling of various plant hormones (abscisic acid, auxin and brassinosteroids), ubiquitin proteasome system, and signaling through Reactive Oxygen Species (ROS). Our findings suggested a complex and multi-level regulatory system modulating response to drought stress in B. napus.

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Pathway studio—the analysis and navigation of molecular networks

Abstract: PathwayAssist is available for commercial licensing from Ariadne Genomics, Inc. The light version with limited functionality will be available for free for academic users at www.ariadnegenomics.com/downloads/.

Cited by 614 publications

References 2 publications

Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

Time course investigation of PPARα- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression

Mining expressed sequence tags of rapeseed (Brassica napus L.) to predict the drought responsive regulatory network

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