Data_Sheet_2_Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis.CSV

Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP39151). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.</p

SNP-gene-pathway network.

The network displays 580 SNPs (green diamonds) located in the selected region for 365 genes (circles) present in 117 pathway clusters (blue squares). Black symbols indicate genes with ten or more connections to pathway clusters, and triangles indicate genes with a positive DisGeNET score (note that these are all black). The disconnected SNP-gene-pathway subnetworks are shown on the left, framed in black.</p

Data_Sheet_7_Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis.XLSX

Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP39151). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.</p

Presentation_1_Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis.PDF

Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP39151). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.</p

Data_Sheet_4_Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis.XLSX

Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP39151). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.</p

Data_Sheet_6_Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis.XLSX

Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP39151). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.</p

From SNPs to pathways: Biological interpretation of type 2 diabetes (T2DM) genome wide association study (GWAS) results

<div><p>Genome-wide association studies (GWAS) have become a common method for discovery of gene-disease relationships, in particular for complex diseases like Type 2 Diabetes Mellitus (T2DM). The experience with GWAS analysis has revealed that the genetic risk for complex diseases involves cumulative, small effects of many genes and only some genes with a moderate effect. In order to explore the complexity of the relationships between T2DM genes and their potential function at the process level as effected by polymorphism effects, a secondary analysis of a GWAS meta-analysis is presented. Network analysis, pathway information and integration of different types of biological information such as eQTLs and gene-environment interactions are used to elucidate the biological context of the genetic variants and to perform an analysis based on data visualization. We selected a T2DM dataset from a GWAS meta-analysis, and extracted 1,971 SNPs associated with T2DM. We mapped 580 SNPs to 360 genes, and then selected 460 pathways containing these genes from the curated collection of WikiPathways. We then created and analyzed SNP-gene and SNP-gene-pathway network modules in Cytoscape. A focus on genes with robust connections to pathways permitted identification of many T2DM pertinent pathways. However, numerous genes lack literature evidence of association with T2DM. We also speculate on the genes in specific network structures obtained in the SNP-gene network, such as gene-SNP-gene modules. Finally, we selected genes relevant to T2DM from our SNP-gene-pathway network, using different sources that reveal gene-environment interactions and eQTLs. We confirmed functions relevant to T2DM for many genes and have identified some—<i>LPL</i> and <i>APOB</i>—that require further validation to clarify their involvement in T2DM.</p></div

Workflow of GWAS data analysis.

<p>The data processing, online resources and tools used to perform the GWAS data analysis and visualization, as described in Materials and Methods.</p

Summary of the relevant genes detected in the secondary analysis of T2DM GWAS study.

<p>Summary of the relevant genes detected in the secondary analysis of T2DM GWAS study.</p

Data_Sheet_3_Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis.PDF

Angiopoietin like protein 8 (ANGPTL8) is a newly identified hormone with unique nature due to its ability to regulate both glucose and lipid metabolic pathways. It is characterized as an important molecular player of insulin induced nutrient storage and utilization pathway during fasting to re-feeding metabolic transition. Several studies have contributed to increase our knowledge regarding its function and mechanism of action. Moreover, its altered expression levels have been observed in Insulin Resistance, Diabetes Mellitus (Types I & II) and Non Alcohlic Fatty Liver Disease emphasizing its assessment as a drug target. However, there is still a great deal of information that remains to be investigated including its associated biological processes, partner proteins in these processes, its regulators and its association with metabolic pathogenesis. In the current study, the analysis of a transcriptomic data set was performed for functional assessment of ANGPTL8 in liver. Weighted Gene Co-expression Network Analysis coupled with pathway analysis tools was performed to identify genes that are significantly co-expressed with ANGPTL8 in liver and investigate their presence in biological pathways. Gene ontology term enrichment analysis was performed to select the gene ontology classes that over-represent the hepatic ANGPTL8-co-expressed genes. Moreover, the presence of diabetes linked SNPs within the genes set co-expressed with ANGPTL8 was investigated. The co-expressed genes of ANGPTL8 identified in this study (n = 460) provides narrowed down list of molecular targets which are either co-regulated with it and/or might be regulation partners at different levels of interaction. These results are coherent with previously demonstrated roles and regulators of ANGPTL8. Specifically, thirteen co-expressed genes (MAPK8, CYP3A4, PIK3R2, PIK3R4,PRKAB2, G6PC, MAP3K11, FLOT1, PIK3C2G, SHC1, SLC16A2, and RAPGEF1) are also present in the literature curated pathway of ANGPTL8 (WP39151). Moreover, the gene-SNP analysis of highly associated biological processes with ANGPTL8 revealed significant genetic signals associated to Diabetes Mellitus and similar phenotypic traits. It provides meaningful insights on the influencing genes involved and co-expressed in these pathways. Findings of this study have implications in functional characterization of ANGPTL8 with emphasis on the identified genes and pathways and their possible involvement in the pathogenesis of Diabetes Mellitus and Insulin Resistance.</p