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pmid:30678306

Integrative Analyses of Genes Associated with Subcutaneous Insulin Resistance.

Manoj Kumar Pujar · Basavaraj Vastrad · Chanabasayya Vastrad

Biomolecules · 2019 doi:10.3390/biom9020037

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Integrative Analyses of Genes Associated with Subcutaneous Insulin Resistance.
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10.3390/biom9020037
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Manoj Kumar Pujar
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Basavaraj Vastrad
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Chanabasayya Vastrad
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Biomolecules
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2019
abstract
: Insulin resistance is present in the majority of patients with non-insulin-dependent diabetes mellitus (NIDDM) and obesity. In this study, we aimed to investigate the key genes and potential molecular mechanism in insulin resistance. Expression profiles of the genes were extracted from the Gene Expression Omnibus (GEO) database. Pathway and Gene Ontology (GO) enrichment analyses were conducted at Enrichr. The protein⁻protein interaction (PPI) network was settled and analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database constructed by Cytoscape software. Modules were extracted and identified by the PEWCC1 plugin. The microRNAs (miRNAs) and transcription factors (TFs) which control the expression of differentially expressed genes (DEGs) were analyzed using the NetworkAnalyst algorithm. A database (GSE73108) was downloaded from the GEO databases. Our results identified 873 DEGs (435 up-regulated and 438 down-regulated) genetically associated with insulin resistance. The pathways which were enriched were pathways in complement and coagulation cascades and complement activation for up-regulated DEGs, while biosynthesis of amino acids and the Notch signaling pathway were among the down-regulated DEGs. Showing GO enrichment were cardiac muscle cell⁻cardiac muscle cell adhesion and microvillus membrane for up-regulated DEGs and negative regulation of osteoblast differentiation and dendrites for down-regulated DEGs. Subsequently, myosin VB (MYO5B), discs, large homolog 2(DLG2), axin 2 (AXIN2), protein tyrosine kinase 7 (PTK7), Notch homolog 1 (NOTCH1), androgen receptor (AR), cyclin D1 (CCND1) and Rho family GTPase 3 (RND3) were diagnosed as the top hub genes in the up- and down-regulated PPI network and modules. In addition, GATA binding protein 6 (GATA6) , ectonucleotide pyrophosphatase/phosphodiesterase 5 (ENPP5), cyclin D1 (CCND1) and tubulin, beta 2A (TUBB2A) were diagnosed as the top hub genes in the up- and down-regulated target gene⁻miRNA network, while tubulin, beta 2A (TUBB2A), olfactomedin-like 1 (OLFML1), prostate adrogen-regulated mucin-like protein 1 (PARM1) and aldehyde dehydrogenase 4 family, member A1 (ALDH4A1)were diagnosed as the top hub genes in the up- and down-regulated target gene⁻TF network. The current study based on the GEO database provides a novel understanding regarding the mechanism of insulin resistance and may provide novel therapeutic targets.
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The DEGs between omental adipose tissue samples with insulin resistance and subcutaneous adipose tissue samples with insulin resistance were screened using the limma (linear models for microarray data) package of R software (version 3.5.1) [23]. The Benjamini and Hochberg false discovery rate (FDR) was applied to provide a balance between the discovery of statistically significant genes and the limitations of false positives.
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sections[4] "2.2. Identification of Differentially Expressed Geness" paragraph 2
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The DEGs between omental adipose tissue samples with insulin resistance and subcutaneous adipose tissue samples with insulin resistance were screened using the limma (linear models for microarray data) package of R software (version 3.5.1) [23]. The Benjamini and Hochberg false discovery rate (FDR) was applied to provide a balance between the discovery of statistically significant genes and the limitations of false positives.
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A gene expression dataset (GSE73108) was downloaded from GEO (Illumina HumanHT-12 V4.0 expression bead chip GPL10558 Platform, San Diego, CA, USA); this dataset was submitted by Wentworth et al. [22]. The GSE73108 dataset contained six omental adipose tissue samples with insulin resistance and six subcutaneous adipose tissue samples with insulin resistance. The DEGs between omental adipose tissue samples with insulin resistance and subcutaneous adipose tissue samples with insulin resistance were screened using the limma (linear models for microarray data) package of R software (version 3.5.1) [23].
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sections[3] "2.1. Microarray Data" paragraph 2
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A gene expression dataset (GSE73108) was downloaded from GEO (Illumina HumanHT-12 V4.0 expression bead chip GPL10558 Platform, San Diego, CA, USA); this dataset was submitted by Wentworth et al.
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The GSE73108 dataset contained six omental adipose tissue samples with insulin resistance and six subcutaneous adipose tissue samples with insulin resistance.
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sections[4] "2.2. Identification of Differentially Expressed Geness" paragraph 2
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The DEGs between omental adipose tissue samples with insulin resistance and subcutaneous adipose tissue samples with insulin resistance were screened using the limma (linear models for microarray data) package of R software (version 3.5.1) [23].
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A gene expression dataset (GSE73108) was downloaded from GEO (Illumina HumanHT-12 V4.0 expression bead chip GPL10558 Platform, San Diego, CA, USA); this dataset was submitted by Wentworth et al. [22]. The GSE73108 dataset contained six omental adipose tissue samples with insulin resistance and six subcutaneous adipose tissue samples with insulin resistance. The DEGs between omental adipose tissue samples with insulin resistance and subcutaneous adipose tissue samples with insulin resistance were screened using the limma (linear models for microarray data) package of R software (version 3.5.1) [23].
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The DEGs between omental adipose tissue samples with insulin resistance and subcutaneous adipose tissue samples with insulin resistance were screened using the limma (linear models for microarray data) package of R software (version 3.5.1) [23]. The Benjamini and Hochberg false discovery rate (FDR) was applied to provide a balance between the discovery of statistically significant genes and the limitations of false positives.
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The pathways which were enriched were pathways in complement and coagulation cascades and complement activation for up-regulated DEGs, while biosynthesis of amino acids and the Notch signaling pathway were among the down-regulated DEGs. Showing GO enrichment were cardiac muscle cell⁻cardiac muscle cell adhesion and microvillus membrane for up-regulated DEGs and negative regulation of osteoblast differentiation and dendrites for down-regulated DEGs. Subsequently, myosin VB (MYO5B), discs, large homolog 2(DLG2), axin 2 (AXIN2), protein tyrosine kinase 7 (PTK7), Notch homolog 1 (NOTCH1), androgen receptor (AR), cyclin D1 (CCND1) and Rho family GTPase 3 (RND3) were diagnosed as the top hub genes in the up- and down-regulated PPI network and modules. 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