Limits...
Integrative bioinformatics analysis of genomic and proteomic approaches to understand the transcriptional regulatory program in coronary artery disease pathways.

Vangala RK, Ravindran V, Ghatge M, Shanker J, Arvind P, Bindu H, Shekar M, Rao VS - PLoS ONE (2013)

Bottom Line: Our present work focuses on understanding the regulatory mechanisms at transcriptional level by identifying the core and specific transcription factors that regulate the coronary artery disease associated pathways.These network modules in turn comprise of biomarkers from different pathways showing that the core regulatory transcription factors may work together in differential regulation of several pathways potentially leading to the disease.This kind of analysis can enhance the elucidation of mechanisms in the disease and give better strategies of developing multimarker module based risk predictions.

View Article: PubMed Central - PubMed

Affiliation: Tata Proteomics and Coagulation Department, Thrombosis Research Institute, Bangalore, Karnataka, India. rajani@triindia.org.in

ABSTRACT
Patients with cardiovascular disease show a panel of differentially regulated serum biomarkers indicative of modulation of several pathways from disease onset to progression. Few of these biomarkers have been proposed for multimarker risk prediction methods. However, the underlying mechanism of the expression changes and modulation of the pathways is not yet addressed in entirety. Our present work focuses on understanding the regulatory mechanisms at transcriptional level by identifying the core and specific transcription factors that regulate the coronary artery disease associated pathways. Using the principles of systems biology we integrated the genomics and proteomics data with computational tools. We selected biomarkers from 7 different pathways based on their association with the disease and assayed 24 biomarkers along with gene expression studies and built network modules which are highly regulated by 5 core regulators PPARG, EGR1, ETV1, KLF7 and ESRRA. These network modules in turn comprise of biomarkers from different pathways showing that the core regulatory transcription factors may work together in differential regulation of several pathways potentially leading to the disease. This kind of analysis can enhance the elucidation of mechanisms in the disease and give better strategies of developing multimarker module based risk predictions.

Show MeSH

Related in: MedlinePlus

Modulation of m-RNA and protein expression profiles.a. Fold change in the mRNA expression of biomarkers from microarray data. b: Fold change in the expression of biomarkers at protein level.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585295&req=5

pone-0057193-g003: Modulation of m-RNA and protein expression profiles.a. Fold change in the mRNA expression of biomarkers from microarray data. b: Fold change in the expression of biomarkers at protein level.

Mentions: The mRNA expression in 20 subjects (10 affected and 10 unaffected subjects) and protein expression levels in 816 subjects (408 affected and 408 unaffected subjects) of 7 pathways representative biomarkers were performed. The mRNA expression levels of the 24 biomarkers (fibrinogen isoforms, alpha, beta and gamma were evaluated individually) were taken from the microarray experiments (figure 3a). The data suggests that 5 biomarkers (Factor VII, IL8, HSP70, HSP60 and HSP27) were significantly differentially expressed at the mRNA level. Furthermore, we assayed 24 biomarker proteins (whole fibrinogen was evaluated in the protein study) (figure 3b) and found that Adiponectin, Leptin, Clusterin, Factor VII, Fibrinogen, MMP9, sPLA2, Myeloperoxidase, HSP70 and HSP60 were significantly differentially expressed.


Integrative bioinformatics analysis of genomic and proteomic approaches to understand the transcriptional regulatory program in coronary artery disease pathways.

Vangala RK, Ravindran V, Ghatge M, Shanker J, Arvind P, Bindu H, Shekar M, Rao VS - PLoS ONE (2013)

Modulation of m-RNA and protein expression profiles.a. Fold change in the mRNA expression of biomarkers from microarray data. b: Fold change in the expression of biomarkers at protein level.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585295&req=5

pone-0057193-g003: Modulation of m-RNA and protein expression profiles.a. Fold change in the mRNA expression of biomarkers from microarray data. b: Fold change in the expression of biomarkers at protein level.
Mentions: The mRNA expression in 20 subjects (10 affected and 10 unaffected subjects) and protein expression levels in 816 subjects (408 affected and 408 unaffected subjects) of 7 pathways representative biomarkers were performed. The mRNA expression levels of the 24 biomarkers (fibrinogen isoforms, alpha, beta and gamma were evaluated individually) were taken from the microarray experiments (figure 3a). The data suggests that 5 biomarkers (Factor VII, IL8, HSP70, HSP60 and HSP27) were significantly differentially expressed at the mRNA level. Furthermore, we assayed 24 biomarker proteins (whole fibrinogen was evaluated in the protein study) (figure 3b) and found that Adiponectin, Leptin, Clusterin, Factor VII, Fibrinogen, MMP9, sPLA2, Myeloperoxidase, HSP70 and HSP60 were significantly differentially expressed.

Bottom Line: Our present work focuses on understanding the regulatory mechanisms at transcriptional level by identifying the core and specific transcription factors that regulate the coronary artery disease associated pathways.These network modules in turn comprise of biomarkers from different pathways showing that the core regulatory transcription factors may work together in differential regulation of several pathways potentially leading to the disease.This kind of analysis can enhance the elucidation of mechanisms in the disease and give better strategies of developing multimarker module based risk predictions.

View Article: PubMed Central - PubMed

Affiliation: Tata Proteomics and Coagulation Department, Thrombosis Research Institute, Bangalore, Karnataka, India. rajani@triindia.org.in

ABSTRACT
Patients with cardiovascular disease show a panel of differentially regulated serum biomarkers indicative of modulation of several pathways from disease onset to progression. Few of these biomarkers have been proposed for multimarker risk prediction methods. However, the underlying mechanism of the expression changes and modulation of the pathways is not yet addressed in entirety. Our present work focuses on understanding the regulatory mechanisms at transcriptional level by identifying the core and specific transcription factors that regulate the coronary artery disease associated pathways. Using the principles of systems biology we integrated the genomics and proteomics data with computational tools. We selected biomarkers from 7 different pathways based on their association with the disease and assayed 24 biomarkers along with gene expression studies and built network modules which are highly regulated by 5 core regulators PPARG, EGR1, ETV1, KLF7 and ESRRA. These network modules in turn comprise of biomarkers from different pathways showing that the core regulatory transcription factors may work together in differential regulation of several pathways potentially leading to the disease. This kind of analysis can enhance the elucidation of mechanisms in the disease and give better strategies of developing multimarker module based risk predictions.

Show MeSH
Related in: MedlinePlus