Cluster analysis and phylogenetic relationship in biomarker identification of type 2 diabetes and nephropathy

Guttula, Satya Vani; Rao, Allam Appa; Sridhar, G. R.; Chakravarthy, M S; Nageshwararo, Kunjum; Rao, Paturi Vishnupriya

doi:10.4103/0973-3930.60003

Cited by 26 publications

(18 citation statements)

References 17 publications

(17 reference statements)

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“…Furthermore, Ada has been proposed as a potential biomarker of type 2 DM and diabetic nephropathy [20]. These studies provide sound evidence for the reliability of the co-differentially-expressed genes found in the present study.…”

Section: Discussionsupporting

confidence: 79%

Gadd45α: A Novel Diabetes-Associated Gene Potentially Linking Diabetic Cardiomyopathy and Baroreflex Dysfunction

et al. 2012

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Both diabetic cardiomyopathy (DCM) and baroreflex dysfunction independently contribute to sudden cardiac death (SCD), however the inherent connections between them under diabetic state remains unclear. As microRNAs (miRNAs) have been reported to participate in various physiological and pathological processes, we presume they may also be involved in DCM and DM-induced impairment of baroreflex sensitivity. Two sets of gene expression profiles data from streptozotocin (STZ)-induced diabetic heart and diabetic dorsal root ganglia (DDRG) were retrieved from GEO and ArrayExpress. Co-differentially-expressed genes in diabetic heart and DDRG were identified by t test and intersection analysis. Human Protein Reference Database (HPRD) was applied to find direct interacting proteins of Gadd45α. Differentially-expressed miRNAs in left ventricle from 4-week STZ-induced diabetic rats were screened by miRNA microarray. Expression of miR-499 and its regulating effect on Gadd45α were then verified by quantitative real-time PCR (qRT-PCR), western blot, computational predication, and dual-luciferase reporter analysis. Four co-differentially-expressed genes in DCM and DDRG were identified. Among these genes, Gadd45α has 16 direct interacting proteins and 11 of them are documentedly associated with DM. Accompanied with significantly increased miR-499 expression, Gadd45α expression was increased at mRNA level but decreased at protein level in both diabetic heart and nucleus ambiguous. Furthermore, miR-499 was confirmed negatively regulating Gadd45α by targeting its 3′UTR. Collectively, reduced Gadd45α protein expression by forced miR-499 expression indicated it's a diabetes-associated gene which might potentially be involved in both DCM and DM-induced baroreflex dysfunction.

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Section: Discussionsupporting

confidence: 79%

Gadd45α: A Novel Diabetes-Associated Gene Potentially Linking Diabetic Cardiomyopathy and Baroreflex Dysfunction

et al. 2012

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“…Furthermore, BDNF gene polymorphism is associated with vasoconstriction [30]. The BDNF-associated gene is also functionally responsible for type 2 diabetic nephropathy, as determined through previously reported microarray analyses [31]. However, in this subgroup analysis of the ADDM study, we observed an inverse correlation between changes in eGFR and changes in the serum BDNF.…”

Section: Discussionmentioning

confidence: 53%

Assessment of Glomerular Filtration Rate Based on Alterations of Serum Brain-Derived Neurotrophic Factor in Type 2 Diabetic Subjects Treated with Amlodipine/Benazepril or Valsartan/Hydrochlorothiazide

et al. 2015

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Background. Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. Methods. In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. Results. Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r = −0.264, P = 0.021) but not in the 77 subjects treated with benazepril/amlodipine (r = −0.025, P = 0.862). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (−8.8 ± 14.9 mL/min/1.73 m2; P < 0.001). Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between −0.887 and −0.076, P = 0.020). Conclusions. Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril.

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“…As an example, Zheng et al applied a hybrid of K‐means and SVM algorithms in breast cancer diagnosis. In addition, N. Heintzman et al developed algorithms making use of the clustering technique (having chromatin signatures of the regulatory elements as a parameter) for predicting promoters and enhancers in the human genome, Wózniak et al applied a hierarchical clustering method in head and neck cancer, among other related papers …”

Section: Introductionmentioning

confidence: 99%

Analysis of the nucleotide content of Escherichia coli promoter sequences related to the alternative sigma factors

Dall'Alba

Casa

Notari

et al. 2018

J of Molecular Recognition

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Promoters are DNA sequences located upstream of the transcription start site of genes. In bacteria, the RNA polymerase enzyme requires additional subunits, called sigma factors (σ) to begin specific gene transcription in distinct environmental conditions. Currently, promoter prediction still poses many challenges due to the characteristics of these sequences. In this paper, the nucleotide content of Escherichia coli promoter sequences, related to five alternative σ factors, was analyzed by a machine learning technique in order to provide profiles according to the σ factor which recognizes them. For this, the clustering technique was applied since it is a viable method for finding hidden patterns on a data set. As a result, 20 groups of sequences were formed, and, aided by the Weblogo tool, it was possible to determine sequence profiles. These found patterns should be considered for implementing computational prediction tools. In addition, evidence was found of an overlap between the functions of the genes regulated by different σ factors, suggesting that DNA structural properties are also essential parameters for further studies.

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Cluster analysis and phylogenetic relationship in biomarker identification of type 2 diabetes and nephropathy

Cited by 26 publications

References 17 publications

Gadd45α: A Novel Diabetes-Associated Gene Potentially Linking Diabetic Cardiomyopathy and Baroreflex Dysfunction

Gadd45α: A Novel Diabetes-Associated Gene Potentially Linking Diabetic Cardiomyopathy and Baroreflex Dysfunction

Assessment of Glomerular Filtration Rate Based on Alterations of Serum Brain-Derived Neurotrophic Factor in Type 2 Diabetic Subjects Treated with Amlodipine/Benazepril or Valsartan/Hydrochlorothiazide

Analysis of the nucleotide content of Escherichia coli promoter sequences related to the alternative sigma factors

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