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Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset.

He K, Lv W, Zhang Q, Wang Y, Tao L, Liu D - Int. J. Mol. Med. (2015)

Bottom Line: As a result, 10 upregulated pathways, including the type I diabetes mellitus and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as 59 downregulated pathways, including the ErbB signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway, were identified as DR‑related pathways.Finally, co-expression networks of related pathways were constructed using the significant core genes and TFs, such as PPARγ and SMAD4.The results of our study may enhance our understanding of the molecular mechanisms associated DR at the genome-wide level.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, Anhui 230601, P.R. China.

ABSTRACT
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, which causes visual disability and blindness. Several studies have used gene expression profiling of DR to identify the key genes involved in this process; however, few studies have focused on the associated pathways and transcription factors (TFs), or on the co-expression patterns at the multiple pathways level. In this study, we employed a microarray dataset from the public database library of the Gene Expression Omnibus (GEO) associated with DR and applied gene set enrichment analysis (GSEA) to this dataset and performed candidate TF selection. As a result, 10 upregulated pathways, including the type I diabetes mellitus and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as 59 downregulated pathways, including the ErbB signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway, were identified as DR‑related pathways. The majority of these pathways have been previously identified, but some were novel. Finally, co-expression networks of related pathways were constructed using the significant core genes and TFs, such as PPARγ and SMAD4. The results of our study may enhance our understanding of the molecular mechanisms associated DR at the genome-wide level.

No MeSH data available.


Related in: MedlinePlus

The coregulated pathways network related to diabetic retinopathy (DR) was established based on the 48 significant pathways identified by gene set enrichment analysis (GSEA). The names in red boxes represent 6 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps, and the names of significant pathways (upregulated pathways shown in red text and downregulated pathways shown in green) associated with DR.
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f1-ijmm-36-01-0103: The coregulated pathways network related to diabetic retinopathy (DR) was established based on the 48 significant pathways identified by gene set enrichment analysis (GSEA). The names in red boxes represent 6 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps, and the names of significant pathways (upregulated pathways shown in red text and downregulated pathways shown in green) associated with DR.

Mentions: Compared to the approach of DEGs, the strategy of GSEA that we used in this study is likely to be more powerful than conventional single-gene methods in the study of complex diseases, in which many genes make subtle contributions. According to our GSEA of the dataset of 5 samples, achieved by comparing the DR to the CT samples, there were 69 significant pathways associated with DR, whose P-values were <0.05, including 10 upregulated and 59 downregulated pathways. The coregulated pathways network is highlighted in Fig. 1 (red text indicates upregulated pathways, and green text indicates downregulated pathways). Furthermore, the details of significant genes in these 69 pathways related to DR are available upon request, as is the information on probe set ID and gene symbol. Among these 69 pathways associated with DR, the samples were classified and divided into DR and CT groups by clustering. For example, based on the expression of 86 significant genes whose significance level P-value was <0.05 in the downregulated ErbB signaling pathway, which may be clustered into 7 groups of gene sets (Fig. 2; group A-G), 5 samples were clustered into 2 groups, with DR-1, DR-2 and DR-3 in one group and CT-1 and CT-2 in the other group. Similarly, in the downregulated mammalian target of rapamycin (mTOR) pathway, 5 samples were also grouped, as CT-1 and CT-2 in the CT group and DR-1, DR-2 and DR-3 in the DR group (Fig. 3). The 52 genes involved in the mTOR signaling pathway may also be clustered into 4 groups of gene sets (Fig. 3, group A-D). Moreover, in the upregulated peroxisome proliferator-activated receptor (PPAR) pathway, 5 samples were also clustered into 2 groups, with CT-1 and CT-2 in one group and DR-1, DR-2 and DR-3 in the other group (Fig. 4). Furthermore, 71 genes were involved in the PPAR signaling pathway associated with DR, which may be clustered into 6 groups of gene sets (Fig. 4, group A–F). Moreover, based on the KEGG pathway maps in the KEGG database (http://www.genome.jp/kegg/), the 69 significant pathways could be mapped into 6 functional classes: cellular processes, environmental information processing, genetic information processing, human diseases, metabolism and organismal systems. The details of the pathways involved in each class are described in Tables I–V.


Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset.

He K, Lv W, Zhang Q, Wang Y, Tao L, Liu D - Int. J. Mol. Med. (2015)

The coregulated pathways network related to diabetic retinopathy (DR) was established based on the 48 significant pathways identified by gene set enrichment analysis (GSEA). The names in red boxes represent 6 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps, and the names of significant pathways (upregulated pathways shown in red text and downregulated pathways shown in green) associated with DR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494587&req=5

f1-ijmm-36-01-0103: The coregulated pathways network related to diabetic retinopathy (DR) was established based on the 48 significant pathways identified by gene set enrichment analysis (GSEA). The names in red boxes represent 6 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps, and the names of significant pathways (upregulated pathways shown in red text and downregulated pathways shown in green) associated with DR.
Mentions: Compared to the approach of DEGs, the strategy of GSEA that we used in this study is likely to be more powerful than conventional single-gene methods in the study of complex diseases, in which many genes make subtle contributions. According to our GSEA of the dataset of 5 samples, achieved by comparing the DR to the CT samples, there were 69 significant pathways associated with DR, whose P-values were <0.05, including 10 upregulated and 59 downregulated pathways. The coregulated pathways network is highlighted in Fig. 1 (red text indicates upregulated pathways, and green text indicates downregulated pathways). Furthermore, the details of significant genes in these 69 pathways related to DR are available upon request, as is the information on probe set ID and gene symbol. Among these 69 pathways associated with DR, the samples were classified and divided into DR and CT groups by clustering. For example, based on the expression of 86 significant genes whose significance level P-value was <0.05 in the downregulated ErbB signaling pathway, which may be clustered into 7 groups of gene sets (Fig. 2; group A-G), 5 samples were clustered into 2 groups, with DR-1, DR-2 and DR-3 in one group and CT-1 and CT-2 in the other group. Similarly, in the downregulated mammalian target of rapamycin (mTOR) pathway, 5 samples were also grouped, as CT-1 and CT-2 in the CT group and DR-1, DR-2 and DR-3 in the DR group (Fig. 3). The 52 genes involved in the mTOR signaling pathway may also be clustered into 4 groups of gene sets (Fig. 3, group A-D). Moreover, in the upregulated peroxisome proliferator-activated receptor (PPAR) pathway, 5 samples were also clustered into 2 groups, with CT-1 and CT-2 in one group and DR-1, DR-2 and DR-3 in the other group (Fig. 4). Furthermore, 71 genes were involved in the PPAR signaling pathway associated with DR, which may be clustered into 6 groups of gene sets (Fig. 4, group A–F). Moreover, based on the KEGG pathway maps in the KEGG database (http://www.genome.jp/kegg/), the 69 significant pathways could be mapped into 6 functional classes: cellular processes, environmental information processing, genetic information processing, human diseases, metabolism and organismal systems. The details of the pathways involved in each class are described in Tables I–V.

Bottom Line: As a result, 10 upregulated pathways, including the type I diabetes mellitus and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as 59 downregulated pathways, including the ErbB signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway, were identified as DR‑related pathways.Finally, co-expression networks of related pathways were constructed using the significant core genes and TFs, such as PPARγ and SMAD4.The results of our study may enhance our understanding of the molecular mechanisms associated DR at the genome-wide level.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, Anhui 230601, P.R. China.

ABSTRACT
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, which causes visual disability and blindness. Several studies have used gene expression profiling of DR to identify the key genes involved in this process; however, few studies have focused on the associated pathways and transcription factors (TFs), or on the co-expression patterns at the multiple pathways level. In this study, we employed a microarray dataset from the public database library of the Gene Expression Omnibus (GEO) associated with DR and applied gene set enrichment analysis (GSEA) to this dataset and performed candidate TF selection. As a result, 10 upregulated pathways, including the type I diabetes mellitus and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as 59 downregulated pathways, including the ErbB signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway, were identified as DR‑related pathways. The majority of these pathways have been previously identified, but some were novel. Finally, co-expression networks of related pathways were constructed using the significant core genes and TFs, such as PPARγ and SMAD4. The results of our study may enhance our understanding of the molecular mechanisms associated DR at the genome-wide level.

No MeSH data available.


Related in: MedlinePlus