Network-Centric Identification of Disease Co-Occurrences: A Systems Biology Approach

Complex diseases that occur by perturbations of molecular pathways and genetic factors result in pathophysiology of diseases. Network-centric systems biology approaches play an important role in understanding disease complexity. Diabetes, cardiovascular disease and depression are such complex diseases that have been reported to be comorbid in various epidemiological studies but there are no reports of the genetic and underlying factors which may be responsible for their reported co-occurrences. The present study was undertaken to investigate the molecular factors responsible for co-occurrence of diabetes, depression and cardiovascular disease using in-silico network systems biology approach. Genes common amongst these three diseases were retrieved from DisGeNET, a database of human diseases and their interactions were retrieved from STRING database. The resulting network containing 99 nodes (which represent genes) and 1252 edges (which represent various interactions between nodes) was analyzed using Cytoscape v: 3.7.2 and its various plug-ins i.e. ClusterONE, Cytohubba, ClueGO and Cluepedia. The hub genes identified in the present study namely IL1B, VEGFA, LEP, CAT, CXCL8, PLG, IL6, IL10, PTGS2, TLR4 and AKT1 were found to be enriched in various metabolic pathways and several mechanisms such as inflammation. These genes and their protein products may act as potential biomarkers for early detection of predisposition to diseases and potential therapeutic targets based on the common molecular underpinnings of co-occurrence of diabetes, depression and cardiovascular disease.

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Integrative Systems Biology Approaches to Identify Potential Biomarkers and Pathways of Cervical Cancer

Journal of Personalized Medicine ◽

10.3390/jpm11050363 ◽

2021 ◽

Vol 11 (5) ◽

pp. 363

Author(s):

Arafat Rahman Oany ◽

Mamun Mia ◽

Tahmina Pervin ◽

Salem Ali Alyami ◽

Mohammad Ali Moni

Keyword(s):

Cervical Cancer ◽

Systems Biology ◽

Differentially Expressed Genes ◽

Inflammatory Responses ◽

Profile Analysis ◽

Target Identification ◽

Regulatory Genes ◽

Differentially Expressed ◽

Hub Genes ◽

Potential Biomarkers

Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC retains its fatality rate of about half of the infected population globally. The major screening biomarkers and therapeutic target identification have now become a global concern. In the present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4643 differentially expressed genes. The up-regulatory genes mainly concentrate on immune-inflammatory responses, and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment, and we mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC and are verified by expression profile analysis. From our study, we have found that genes LILRB2 and CYBB play crucial roles in CC, as reported here for the first time. Furthermore, the survivability of the hub genes was also assessed, and among them, finally, CXCR4 has been identified as one of the most potential differentially expressed genes that might play a vital role in the survival of CC patients. Thus, CXCR4 could be used as a prognostic and/or diagnostic biomarker and a drug target for CC.

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Systems biology approaches to epidemiological studies of complex diseases

Wiley Interdisciplinary Reviews Systems Biology and Medicine ◽

10.1002/wsbm.1242 ◽

2013 ◽

Vol 5 (6) ◽

pp. 677-686 ◽

Cited By ~ 5

Author(s):

Hongzhe Li

Keyword(s):

Systems Biology ◽

Complex Diseases ◽

Epidemiological Studies

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Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders

Mediators of Inflammation ◽

10.1155/2016/3634948 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 58

Author(s):

A. Janus ◽

E. Szahidewicz-Krupska ◽

G. Mazur ◽

A. Doroszko

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Endothelial Dysfunction ◽

Metabolic Pathways ◽

Metabolic Disturbances ◽

Lipid Disorders ◽

Cardiometabolic Disorders ◽

Treatment Of Hypertension ◽

The Common

Insulin resistance and other risk factors for atherosclerosis, such as hypertension and hypercholesterolemia, promote endothelial dysfunction and lead to development of metabolic syndrome which constitutes an introduction to cardiovascular disease. The insulin resistance and endothelial dysfunction cross talk between each other by numerous metabolic pathways. Hence, targeting one of these pathologies with pleiotropic treatment exerts beneficial effect on another one. Combined and expletive treatment of hypertension, lipid disorders, and insulin resistance with nonpharmacological interventions and conventional pharmacotherapy may inhibit the transformation of metabolic disturbances to fully developed cardiovascular disease. This paper summarises the common therapeutic targets for insulin resistance, endothelial dysfunction, and vascular inflammatory reaction at molecular level and analyses the potential pleiotropic effects of drugs used currently in management of cardiovascular disease, metabolic syndrome, and diabetes.

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Mechanisms of macrovascular disease in diabetes

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.1542 ◽

2011 ◽

pp. 1955-1959

Author(s):

Peter J. Grant ◽

Mark T. Kearney

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Renal Disease ◽

Macrovascular Disease ◽

Epidemiological Studies ◽

Atheromatous Plaque ◽

The Common ◽

Genetic And Environmental Factors

The virtual epidemic of diabetes that has appeared over the last couple of decades has highlighted the influence of Western lifestyles and obesity on the development of glucose intolerance and associated cardiovascular disease. Two important hypotheses need consideration in contemplating the strong clinical links that exist between diabetes and cardiovascular disease. ◆ The thrifty genotype hypothesis proposed that the development of insulin resistance was an innate biochemical mechanism that acted to conserve energy in times of food shortage as obesity becomes chronic, as in modern life, insulin resistance would lead to the development of type 2 diabetes, thus introducing the concept of exposure as an important pathogenic factor. ◆ The common soil hypothesis argued that diabetes and cardiovascular disease are the same condition underpinned by common genetic and environmental factors. One of the great advances in understanding in the past 20 years has been the observation that insulin resistance is associated with inflammatory and atherothrombotic risk factor clustering to provide a risk ‘mirror’ for the changes observed in the vulnerable atheromatous plaque. This brings together the thrifty and the common soil hypotheses and indicates that physiological fluctuations in weight and insulin resistance seen in relation to variation in food availability become pathological with chronic exposure leading to both type 2 diabetes and cardiovascular disease. As insulin resistance cycles to type 2 diabetes, hyperglycaemia has further detrimental effects on vascular disease through the generation of reactive oxygen species, glycation of longlasting proteins, and direct effects of glucose. Epidemiological studies demonstrate a marked increase in vascular outcomes as individuals move from euglycaemic insulin resistance to type 2 diabetes to reflect this increased risk. Finally, the development of microvascular renal disease amplifies vascular risk further and the combination of hyperglycaemia and renal disease provides a common pathway for increased cardiovascular risk in both type 1 and type 2 diabetes.

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Integrative Systems Biology Approaches to Identify Potential Biomarkers and Pathways of Cervical Cancer

10.20944/preprints202103.0197.v1 ◽

2021 ◽

Author(s):

Arafat Rahman Oany ◽

Mamun Mia ◽

Tahmina Pervin ◽

Salem A. Alyami ◽

Mohammad Ali Moni

Keyword(s):

Cervical Cancer ◽

Systems Biology ◽

Target Identification ◽

Differentially Expressed Gene ◽

Vital Role ◽

Regulatory Genes ◽

Differentially Expressed ◽

Hub Genes ◽

Cancer Pathways ◽

Potential Biomarkers

Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC remains its fatality rate about half of the infected populations globally. The major screening biomarkers and therapeutic target identification have now become a global concern. The present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from the transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4,643 differentially expressed genes. The up-regulatory genes are mainly concentrating on immune-inflammatory response and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment and they were mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC. Furthermore, the survival of the hub genes was also assessed, and among them, finally, CXCR4 has identified as one of the most potential differentially expressed gene that might play a vital role to the survival of CC patients. Thus CXCR4 could be used as a prognostic biomarker and development of a drug target for CC.

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Hyperuricemia as risk factor for cardiovascular disease – what’s new?

Medical alphabet ◽

10.33667/2078-5631-2020-13-5-11 ◽

2020 ◽

pp. 5-11

Author(s):

Yu. V. Zhernakova

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Uric Acid ◽

Cardiovascular Risk ◽

Epidemiological Studies ◽

Point Of View ◽

Medical Society ◽

High Cardiovascular Risk ◽

Management Algorithm ◽

Russian Medical

A significant number of epidemiological studies have shown that hyperuricemia is highly associated with the risk of developing cardiovascular disease, chronic kidney disease, and diabetes. In this connection, increased attention is required to monitor serum uric acid levels in patients, not only from a rheumatological point of view, but also with regard to reducing cardiovascular and renal risks. This article is a review of studies on the association of hyperuricemia with cardiovascular risk and a new consensus for the management of patients with hyperuricemia and high cardiovascular risk, published in december 2019 by a group of experts of the Russian Medical Society for Arterial Hypertension, which, among other things, includes a management algorithm of this category of patients.

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High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad and the Future

Biomedicines ◽

10.3390/biomedicines9080857 ◽

2021 ◽

Vol 9 (8) ◽

pp. 857

Author(s):

Josep Julve ◽

Joan Carles Escolà-Gil

Keyword(s):

Cardiovascular Disease ◽

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Density Lipoprotein ◽

Epidemiological Studies ◽

High Density ◽

High Density Lipoproteins ◽

Atherosclerotic Cardiovascular Disease ◽

Plasma High Density ◽

Low Levels

Epidemiological studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]

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Identification of novel cardiovascular disease associated metabolites using untargeted metabolomics

Biological Chemistry ◽

10.1515/hsz-2020-0331 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Shams Tabrez ◽

Mohammed Razeeth Shait Mohammed ◽

Nasimudeen R. Jabir ◽

Mohammad Imran Khan

Keyword(s):

Cardiovascular Disease ◽

Metabolic Pathways ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Healthy Individuals ◽

Great Opportunity ◽

Pathway Enrichment ◽

Pathophysiological Role ◽

The World ◽

Metabolomic Approach

Abstract Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and N1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, N-acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.

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Interstrain Variability of Human Vaginal Lactobacillus crispatus for Metabolism of Biogenic Amines and Antimicrobial Activity against Urogenital Pathogens

Molecules ◽

10.3390/molecules26154538 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4538

Author(s):

Scarlett Puebla-Barragan ◽

Emiley Watson ◽

Charlotte van der Veer ◽

John A. Chmiel ◽

Charles Carr ◽

...

Keyword(s):

Biogenic Amines ◽

Metabolic Pathways ◽

Vaginal Microbiota ◽

Comparative Genome Analysis ◽

Genetic Traits ◽

Lactobacillus Crispatus ◽

Vaginal Swabs ◽

The Common ◽

Synthesis And Degradation

Lactobacillus crispatus is the dominant species in the vagina of many women. With the potential for strains of this species to be used as a probiotic to help prevent and treat dysbiosis, we investigated isolates from vaginal swabs with Lactobacillus-dominated and a dysbiotic microbiota. A comparative genome analysis led to the identification of metabolic pathways for synthesis and degradation of three major biogenic amines in most strains. However, targeted metabolomic analysis of the production and degradation of biogenic amines showed that certain strains have either the ability to produce or to degrade these compounds. Notably, six strains produced cadaverine, one produced putrescine, and two produced tyramine. These biogenic amines are known to raise vaginal pH, cause malodour, and make the environment more favourable to vaginal pathogens. In vitro experiments confirmed that strains isolated from women with a dysbiotic vaginal microbiota have higher antimicrobial effects against the common urogenital pathogens Escherichia coli and Enterococcus faecium. The results indicate that not all L. crispatus vaginal strains appear suitable for probiotic application and the basis for selection should not be only the overall composition of the vaginal microbiota of the host from which they came, but specific biochemical and genetic traits.

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