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Construction of a polycystic ovarian syndrome (PCOS) pathway based on the interactions of PCOS-related proteins retrieved from bibliomic data.

Mohamed-Hussein ZA, Harun S - Theor Biol Med Model (2009)

Bottom Line: Most of the genes were found to be involved in gene and protein expression, cell signaling and metabolism.BiNGO was used to identify the three main ontologies in the protein network: molecular functions, biological processes and cellular components.These include the insulin receptor signaling pathway, steroid biosynthesis, and the regulation of gonadotropin secretion among others.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor, Malaysia. zeti@ukm.my

ABSTRACT
Polycystic ovary syndrome (PCOS) is a complex but frequently occurring endocrine abnormality. PCOS has become one of the leading causes of oligo-ovulatory infertility among premenopausal women. The definition of PCOS remains unclear because of the heterogeneity of this abnormality, but it is associated with insulin resistance, hyperandrogenism, obesity and dyslipidaemia. The main purpose of this study was to identify possible candidate genes involved in PCOS. Several genomic approaches, including linkage analysis and microarray analysis, have been used to look for candidate PCOS genes. To obtain a clearer view of the mechanism of PCOS, we have compiled data from microarray analyses. An extensive literature search identified seven published microarray analyses that utilized PCOS samples. These were published between the year of 2003 and 2007 and included analyses of ovary tissues as well as whole ovaries and theca cells. Although somewhat different methods were used, all the studies employed cDNA microarrays to compare the gene expression patterns of PCOS patients with those of healthy controls. These analyses identified more than a thousand genes whose expression was altered in PCOS patients. Most of the genes were found to be involved in gene and protein expression, cell signaling and metabolism. We have classified all of the 1081 identified genes as coding for either known or unknown proteins. Cytoscape 2.6.1 was used to build a network of protein and then to analyze it. This protein network consists of 504 protein nodes and 1408 interactions among those proteins. One hypothetical protein in the PCOS network was postulated to be involved in the cell cycle. BiNGO was used to identify the three main ontologies in the protein network: molecular functions, biological processes and cellular components. This gene ontology analysis identified a number of ontologies and genes likely to be involved in the complex mechanism of PCOS. These include the insulin receptor signaling pathway, steroid biosynthesis, and the regulation of gonadotropin secretion among others.

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Protein binding node. The protein binding node is connected to 12 other nodes. The protein binding node is the most significant node because it encompasses 331 genes. Of the 468 genes in the PCOS molecular function network, 339 (72.4%) are involved in protein binding and are thereby linked to other protein nodes such as the transcription factors (34 genes), identical proteins (37 genes), protein dimerization (35 genes), receptors (50 genes), protein complexes (13 genes), cyclins (2 genes), enzymes (24 genes), growth factors (13 genes), follistatins (3 genes), and insulin receptor substrates (3 genes).
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Figure 4: Protein binding node. The protein binding node is connected to 12 other nodes. The protein binding node is the most significant node because it encompasses 331 genes. Of the 468 genes in the PCOS molecular function network, 339 (72.4%) are involved in protein binding and are thereby linked to other protein nodes such as the transcription factors (34 genes), identical proteins (37 genes), protein dimerization (35 genes), receptors (50 genes), protein complexes (13 genes), cyclins (2 genes), enzymes (24 genes), growth factors (13 genes), follistatins (3 genes), and insulin receptor substrates (3 genes).

Mentions: The PCOS network was then analyzed with the Biological Networks Gene Ontology (BiNGO) program to identify ontologies involved in the protein network. BiNGO is one of the plugins for Cytoscape 2.6.1. Three ontologies (cellular component, molecular function and biological process) were identified in the BiNGO analysis. Figure 3 shows the results from the BiNGO analysis regarding molecular function. The binding node is the most significant node as it involves 415 of the 468 proteins. The binding node encompasses multiple types of molecular interactions, including protein binding, nucleic acid binding, peptide binding, pattern binding, carbohydrate binding and nucleotide binding. Detailed results are displayed in Figure 4. Other molecular function nodes that may play an important role in the pathogenesis of PCOS include steroid dehydrogenase activity (12 genes) and estradiol 17-beta-dehydrogenase activity (5 genes), among others. The molecular function mode of BiNGO identified three genes (INHBA, ACVR1 and ACVR2A) involved in follistatin binding. Follistatin was also implicated in PCOS by linkage analysis [9]. BiNGO identified several biological processes that maybe involved with PCOS including lipid metabolism (40 genes), regulation of apoptosis (56 genes), insulin receptor signaling (9 genes), steroid biosynthesis (13 genes) and the regulation of gonadotropin secretion (3 genes). Of the 473 genes in biological process genes identified by BiNGO, 40 were involved with lipid metabolism. One of these genes, ALOX15, is a lipoxygenase that was found to be upregulated in omental fat of PCOS patients [19]. ALOX15 may be involved with insulin resistance since a number of lypoxygenase-oxidized fatty acids become leukotrienes, which contribute to the chronic inflammatory condition of PCOS [19]. Laboratory findings support this idea as the inhibition of lipoxygenases was found to enhance the action of insulin in rat models of insulin resistance and type 2 diabetes [32].


Construction of a polycystic ovarian syndrome (PCOS) pathway based on the interactions of PCOS-related proteins retrieved from bibliomic data.

Mohamed-Hussein ZA, Harun S - Theor Biol Med Model (2009)

Protein binding node. The protein binding node is connected to 12 other nodes. The protein binding node is the most significant node because it encompasses 331 genes. Of the 468 genes in the PCOS molecular function network, 339 (72.4%) are involved in protein binding and are thereby linked to other protein nodes such as the transcription factors (34 genes), identical proteins (37 genes), protein dimerization (35 genes), receptors (50 genes), protein complexes (13 genes), cyclins (2 genes), enzymes (24 genes), growth factors (13 genes), follistatins (3 genes), and insulin receptor substrates (3 genes).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2743649&req=5

Figure 4: Protein binding node. The protein binding node is connected to 12 other nodes. The protein binding node is the most significant node because it encompasses 331 genes. Of the 468 genes in the PCOS molecular function network, 339 (72.4%) are involved in protein binding and are thereby linked to other protein nodes such as the transcription factors (34 genes), identical proteins (37 genes), protein dimerization (35 genes), receptors (50 genes), protein complexes (13 genes), cyclins (2 genes), enzymes (24 genes), growth factors (13 genes), follistatins (3 genes), and insulin receptor substrates (3 genes).
Mentions: The PCOS network was then analyzed with the Biological Networks Gene Ontology (BiNGO) program to identify ontologies involved in the protein network. BiNGO is one of the plugins for Cytoscape 2.6.1. Three ontologies (cellular component, molecular function and biological process) were identified in the BiNGO analysis. Figure 3 shows the results from the BiNGO analysis regarding molecular function. The binding node is the most significant node as it involves 415 of the 468 proteins. The binding node encompasses multiple types of molecular interactions, including protein binding, nucleic acid binding, peptide binding, pattern binding, carbohydrate binding and nucleotide binding. Detailed results are displayed in Figure 4. Other molecular function nodes that may play an important role in the pathogenesis of PCOS include steroid dehydrogenase activity (12 genes) and estradiol 17-beta-dehydrogenase activity (5 genes), among others. The molecular function mode of BiNGO identified three genes (INHBA, ACVR1 and ACVR2A) involved in follistatin binding. Follistatin was also implicated in PCOS by linkage analysis [9]. BiNGO identified several biological processes that maybe involved with PCOS including lipid metabolism (40 genes), regulation of apoptosis (56 genes), insulin receptor signaling (9 genes), steroid biosynthesis (13 genes) and the regulation of gonadotropin secretion (3 genes). Of the 473 genes in biological process genes identified by BiNGO, 40 were involved with lipid metabolism. One of these genes, ALOX15, is a lipoxygenase that was found to be upregulated in omental fat of PCOS patients [19]. ALOX15 may be involved with insulin resistance since a number of lypoxygenase-oxidized fatty acids become leukotrienes, which contribute to the chronic inflammatory condition of PCOS [19]. Laboratory findings support this idea as the inhibition of lipoxygenases was found to enhance the action of insulin in rat models of insulin resistance and type 2 diabetes [32].

Bottom Line: Most of the genes were found to be involved in gene and protein expression, cell signaling and metabolism.BiNGO was used to identify the three main ontologies in the protein network: molecular functions, biological processes and cellular components.These include the insulin receptor signaling pathway, steroid biosynthesis, and the regulation of gonadotropin secretion among others.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor, Malaysia. zeti@ukm.my

ABSTRACT
Polycystic ovary syndrome (PCOS) is a complex but frequently occurring endocrine abnormality. PCOS has become one of the leading causes of oligo-ovulatory infertility among premenopausal women. The definition of PCOS remains unclear because of the heterogeneity of this abnormality, but it is associated with insulin resistance, hyperandrogenism, obesity and dyslipidaemia. The main purpose of this study was to identify possible candidate genes involved in PCOS. Several genomic approaches, including linkage analysis and microarray analysis, have been used to look for candidate PCOS genes. To obtain a clearer view of the mechanism of PCOS, we have compiled data from microarray analyses. An extensive literature search identified seven published microarray analyses that utilized PCOS samples. These were published between the year of 2003 and 2007 and included analyses of ovary tissues as well as whole ovaries and theca cells. Although somewhat different methods were used, all the studies employed cDNA microarrays to compare the gene expression patterns of PCOS patients with those of healthy controls. These analyses identified more than a thousand genes whose expression was altered in PCOS patients. Most of the genes were found to be involved in gene and protein expression, cell signaling and metabolism. We have classified all of the 1081 identified genes as coding for either known or unknown proteins. Cytoscape 2.6.1 was used to build a network of protein and then to analyze it. This protein network consists of 504 protein nodes and 1408 interactions among those proteins. One hypothetical protein in the PCOS network was postulated to be involved in the cell cycle. BiNGO was used to identify the three main ontologies in the protein network: molecular functions, biological processes and cellular components. This gene ontology analysis identified a number of ontologies and genes likely to be involved in the complex mechanism of PCOS. These include the insulin receptor signaling pathway, steroid biosynthesis, and the regulation of gonadotropin secretion among others.

Show MeSH
Related in: MedlinePlus