CASCADE_SCAN: mining signal transduction network from high-throughput data based on steepest descent method

Wang, Kai; Hu, Fuyan; Xu, Kejia; Cheng, Hua; Jiang, Meng; Feng, Ruili; Li, Jing; Wen, Tao

doi:10.1186/1471-2105-12-164

Cited by 14 publications

(14 citation statements)

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“…This provided a list of count of genes in each of the above four datasets and the entire mouse genome annotated to each KEGG pathway. Calculation of enrichment P values is based on the following mathematical approach: in a dataset of N genes from entire genome, where M genes are annotated to a particular KEGG pathway, and n genes are differentially expressed, then the probability of having k genes to be differentially expressed and also included in the above KEGG pathway is given by a hypergeometric distribution as described the equation below [ 36 ] …”

Section: Methodsmentioning

confidence: 99%

The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice

et al. 2015

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BackgroundThe hallmark of Type 2 diabetes (T2D) is hyperglycemia, although there are multiple other metabolic abnormalities that occur with T2D, including insulin resistance and dyslipidemia. To advance T2D prevention and develop targeted therapies for its treatment, a greater understanding of the alterations in metabolic tissues associated with T2D is necessary. The aim of this study was to use microarray analysis of gene expression in metabolic tissues from a mouse model of pre-diabetes and T2D to further understand the metabolic abnormalities that may contribute to T2D. We also aimed to uncover the novel genes and pathways regulated by the insulin sensitizing agent (CL-316,243) to identify key pathways and target genes in metabolic tissues that can reverse the diabetic phenotype.MethodsMale MKR mice on an FVB/n background and age matched wild-type (WT) FVB/n mice were used in all experiments. Skeletal muscle, liver and fat were isolated from prediabetic (3 week old) and diabetic (8 week old) MKR mice. Male MKR mice were treated with CL-316,243. Skeletal muscle, liver and fat were isolated after the treatment period. RNA was isolated from the metabolic tissues and subjected to microarray and KEGG database analysis.ResultsSignificant decreases in the expression of mitochondrial and peroxisomal fatty acid oxidation genes were found in the skeletal muscle and adipose tissue of adult MKR mice, and the liver of pre-diabetic MKR mice, compared to WT controls. After treatment with CL-316,243, the circulating glucose and insulin concentrations in the MKR mice improved, an increase in the expression of peroxisomal fatty acid oxidation genes was observed in addition to a decrease in the expression of retinaldehyde dehydrogenases. These genes were not previously known to be regulated by CL-316,243 treatment.ConclusionsThis study uncovers novel genes that may contribute to pharmacological reversal of insulin resistance and T2D and may be targets for treatment. In addition, it explains the lower free fatty acid levels in MKR mice after treatment with CL-316,243 and furthermore, it provides biomarker genes such as ACAA1 and HSD17b4 which could be further probed in a future study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0003-8) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice

et al. 2015

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“…In addition, because the JASPAR database is limited, the transcriptional regulatory network was constructed combined with transcription factor binding sites in the University of California Santa Cruz (USA) genome browser database ( 18 ). Finally, a hypergeometric distribution test ( 19 ) was applied to select the significantly enriched motifs (P≤0.01).…”

Section: Methodsmentioning

confidence: 99%

Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome

Kong¹,

Liu²,

Xu³

2014

Braz J Med Biol Res

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In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs. Finally, a transcriptional regulatory network was constructed, and a hypergeometric distribution test was applied to select for significantly enriched transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were each up-regulated two-fold in Down syndrome samples compared to normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse chromosome 16). The DEGs were significantly enriched in macromolecular complex subunit organization and focal adhesion pathways. Eleven significantly enriched transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs identified in our study provide biomarkers for the understanding of Down syndrome pathogenesis and progression.

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“…TFs act depending on cis -regulatory motif in 5′UTR of their target genes. In order to detect such significant enriched cis-regulatory signals, hypergeometric distribution test was implemented ( 28 ), with a P-value of ≤0.05.…”

Section: Methodsmentioning

confidence: 99%

Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation

Lin

Zhang

Zhao

et al. 2014

International Journal of Molecular Medicine

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Carotid atherosclerosis is a chronic inflammatory disease of the arterial wall. The present study aimed to identify changes in the gene expression and regulatory factors for atherosclerotic plaques of carotid atherosclerosis from an early to an advanced stage. The original data were downloaded from the NCBI GEO database under accession no. GSE28829. Differentially expressed genes (DEGs) were detected by the Robust Multiarray Average (RMA). The enriched Gene Ontology (GO) terms and pathways for DEGs using DAVID were subsequently identified. The transcriptional and microRNA (miRNA) regulatory network were constructed for the DEGs. Cis-regulatory signals were also investigated. More genes were activated in the advanced stage compared with the early stage. IGHG1 and SPP1 were upregulated, while MYBL1 and PLD were downregulated. The upregulated genes in the advanced stage were involved in atherosclerosis-related GO terms such as immune, vascular and cell movement homeostasis. The DEGs were significantly enriched in cell adhesion molecules (CAMs) and the focal adhesion pathway. MMP9 and CFL2 played key roles in the transcriptional regulatory network. Moreover, miR-328 was identified as one of the hubs in the miRNA regulatory network. The results may therefore be used to determine the mechanism involved in carotid atherosclerosis.

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CASCADE_SCAN: mining signal transduction network from high-throughput data based on steepest descent method

Cited by 14 publications

References 50 publications

The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice

The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice

Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome

Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation

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