Papers by GEORGIA BRALIOU
In silico identification and analysis of proteins containing PX phosphoinositide binding domain in Kinetoplastea protists: evolutionary conservation and uniqueness of PX domain-containing protein architectures
Zenodo (CERN European Organization for Nuclear Research), May 29, 2023
BMC Medical Genomics, Nov 27, 2018
Background: Myocardial infarction (MI) is a multifactorial disease with complex pathogenesis, mai... more Background: Myocardial infarction (MI) is a multifactorial disease with complex pathogenesis, mainly the result of the interplay of genetic and environmental risk factors. The regulation of thrombosis, inflammation and cholesterol and lipid metabolism are the main factors that have been proposed thus far to be involved in the pathogenesis of MI. Traditional risk-estimation tools depend largely on conventional risk factors but there is a need for identification of novel biochemical and genetic markers. The aim of the study is to identify differentially expressed genes that are consistently associated with the incidence myocardial infarction (MI), which could be potentially incorporated into the traditional cardiovascular diseases risk factors models. Methods: The biomedical literature and gene expression databases, PubMed and GEO, respectively, were searched following the PRISMA guidelines. The key inclusion criteria were gene expression data derived from case-control studies on MI patients from blood samples. Gene expression datasets regarding the effect of medicinal drugs on MI were excluded. The t-test was applied to gene expression data from case-control studies in MI patients. Results: A total of 162 articles and 174 gene expression datasets were retrieved. Of those a total of 4 gene expression datasets met the inclusion criteria, which contained data on 31,180 loci in 93 MI patients and 89 healthy individuals. Collectively, 626 differentially expressed genes were detected in MI patients as compared to nonaffected individuals at an FDR q-value = 0.01. Of those, 88 genes/gene products were interconnected in an interaction network. Totally, 15 genes were identified as hubs of the network. Conclusions: Functional enrichment analyses revealed that the DEGs and that they are mainly involved in inflammatory/wound healing, RNA processing/transport mechanisms and a yet not fully characterized pathway implicated in RNA transport and nuclear pore proteins. The overlap between the DEGs identified in this study and the genes identified through genetic-association studies is minimal. These data could be useful in future studies on the molecular mechanisms of MI as well as diagnostic and prognostic markers.
The EMBO Journal, 1998
v-ErbA, a mutated thyroid hormone receptor alpha (TRα), is thought to contribute to avian erythro... more v-ErbA, a mutated thyroid hormone receptor alpha (TRα), is thought to contribute to avian erythroblastosis virus (AEV)-induced leukemic transformation by constitutively repressing transcription of target genes. However, the binding of v-ErbA or any unliganded nuclear receptor to a chromatin-embedded response element as well as the role of the N-CoR-SMRT-HDAC co-repressor complex in mediating repression remain hypothetical. Here we identify a v-ErbA-response element, VRE, in an intronic DNase I hypersensitive site (HS2) of the chicken erythroid carbonic anhydrase II (CAII) gene. In vivo footprinting shows that v-ErbA is constitutively bound to this HS2-VRE in transformed, undifferentiated erythroblasts along with other transcription factors like GATA-1. Transfection assays show that the repressed HS2 region can be turned into a potent enhancer in v-ErbAexpressing cells by mutation of the VRE. Differentiation of transformed cells alleviates v-ErbA binding concomitant with activation of CAII transcription. Co-expression of a gag-TRα fusion protein in AEV-transformed cells and addition of ligand derepresses CAII transcription. Treatment of transformed cells with the histone deacetylase inhibitor, trichostatin A, derepresses the endogenous, chromatin-embedded CAII gene, while a transfected HS2-enhancer construct remains repressed. Taken together, our data suggest that v-ErbA prevents CAII activation by 'neutralizing' in cis the activity of erythroid transcription factors.
Genes, Jan 21, 2017
Plastome-genome incompatibility (PGI) is prevalent in several plants including the Zantedeschia s... more Plastome-genome incompatibility (PGI) is prevalent in several plants including the Zantedeschia species, a worldwide commercial flower crop native to South Africa. Generally, hybrids suffering from PGI appear less vigorous and more susceptible than normal plants. Previous reports revealed that the PGI level in interspecific hybrids is correlated with the relatedness of the parental species in the genus Zantedeschia. To provide a basis for utilizing and improving resources in breeding programs, a total of 117 accessions of colored calla lily (Zantedeschia hybrid), collected from New Zealand, the Netherlands and the United States, were genotyped using 31 transferable expressed sequence tags-simple sequence repeats (EST-SSR) markers from the white calla lily (Zantedeschia aethiopica). A moderately high level of genetic diversity was observed, with 111 alleles in total, an observed/expected heterozygosity (Ho/He) of 0.453/0.478, and polymorphism information content (PIC) of 0.26. Geneti...
Nutrients
Stevia (Stevia rebaudiana Bertoni) is an aromatic plant known for its high sweetening power ascri... more Stevia (Stevia rebaudiana Bertoni) is an aromatic plant known for its high sweetening power ascribed to its glycosides. Stevia also contains several bioactive compounds showing antioxidant, antiproliferative, antimicrobial, and anti-inflammatory activities. Since inflammation and oxidative stress play critical roles in the pathogenesis of many diseases, stevia emerges as a promising natural product that could support human health. In this study we set out to investigate the way stevia affects oxidative stress markers (e.g., SOD, CAT, GPx, GSH, MDA) in diseased rats administered stevia leaf extracts or glycosides. To this end, we performed an inclusive literature search, following PRISMA guidelines, and recruited multivariate meta-analysis and meta-regression to synthesize all available data on experimental animal models encountering (a) healthy, (b) diseased, and (c) stevia-treated diseased rats. From the 184 articles initially retrieved, 24 satisfied the eligibility criteria, conta...
International Journal of Molecular Sciences
Kinetoplastea are free living and parasitic protists with unique features among Eukaryota. Pathog... more Kinetoplastea are free living and parasitic protists with unique features among Eukaryota. Pathogenic Kinetoplastea parasites (i.e., Trypanosoma and Leishmania spp.) undergo several developmental transitions essential for survival in their hosts. These transitions require membrane and cytoskeleton reorganizations that involve phosphoinositides (PIs). Phospholipids like PIs are key regulators of vital functions in all eukaryotes including signal transduction, protein transport and sorting, membrane trafficking, and cytoskeleton and membrane remodeling. A large repertoire of PI-metabolizing enzymes and PI-binding proteins/effectors carrying distinct PI-binding modules like the PX (phox homology) module could play significant roles in the life and virulence of pathogenic Kinetoplastea. The aim of this study was to retrieve the entire spectrum of Kinetoplastea protein sequences containing the PX module (PX-proteins), predict their structures, and identify in them evolutionary conserved ...
Pathogens
Leishmaniasis is a neglected tropical disease affecting humans and domesticated animals with high... more Leishmaniasis is a neglected tropical disease affecting humans and domesticated animals with high mortality in endemic countries. The pleiotropy of symptoms and the complicated gold-standard methods make the need for non-invasive, highly sensitive diagnostic tests imperative. Individual studies on molecular-based Leishmania diagnosis in urine show high discrepancy; thus, a data-evidenced comparison of various techniques is necessary. We performed a systematic review and meta-analysis using the bivariate method of diagnostic methods to pool sensitivities and specificities. We investigated the impact of DNA-extraction method, PCR type, amplified locus, host species, leishmaniasis form, and geographical region. The pooled sensitivity was 69.2%. Tests performed with the kit-based DNA extraction method and qPCR outweighed in sensitivity the phenol-chloroform-based and PCR methods, while their combination showed a sensitivity of 79.3%. Amplified locus, human or canine as host and cutaneou...
Μεταγραφική ρύθμιση από το v-erbA, το ογκογονικό ανάλογο του υποδοχέα θυρεοειδούς ορμόνης
Thyroid hormone (T3) exhibits a vast array of profound effects on homeostasis, development, amphi... more Thyroid hormone (T3) exhibits a vast array of profound effects on homeostasis, development, amphibian metamorphosis, differentiation and neoplasia. The action of T3 is mediated via its binding to the cognate thyroid hormone receptor (TR) which in turn binds to specific DNA sequences called thyroid responsive elements (TREs). TR in the presence of T3 activates transcription while unliganded TR leads to repression utilizing a multitude of mechanisms to regulate transcription. The v-ErbA oncoprotein is a mutated viral variant of TRα encoded by the Avian Erythroblastosis virus (AEV). The co-operation of v-erbA with v-erbB, the second oncogene of AEV with tyrosine kinase activity, leads to fatal erythroleukemia as a result of enhanced proliferation and arrest of differentiation. Due to mutations, v-ErbA cannot bind T3 hormone and thus it cannot activate transcription like TR its cellular counterpart. The hypothesis that v-ErbA behaves as a constitutive unliganded TR is attractive but not...
The Pharmacogenomics Journal
Available drugs have been used as an urgent attempt through clinical trials to minimize severe ca... more Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the genedisease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient.
Diagnostics
Coronavirus disease 2019 (COVID-19) initiated global health care challenges such as the necessity... more Coronavirus disease 2019 (COVID-19) initiated global health care challenges such as the necessity for new diagnostic tests. Diagnosis by real-time PCR remains the gold-standard method, yet economical and technical issues prohibit its use in points of care (POC) or for repetitive tests in populations. A lot of effort has been exerted in developing, using, and validating antigen-based tests (ATs). Since individual studies focus on few methodological aspects of ATs, a comparison of different tests is needed. Herein, we perform a systematic review and meta-analysis of data from articles in PubMed, medRxiv and bioRxiv. The bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities was used. Most of the AT types for SARS-CoV-2 were lateral flow immunoassays (LFIA), fluorescence immunoassays (FIA), and chemiluminescence enzyme immunoassays (CLEIA). We identified 235 articles containing data from 220,049 individuals. All ATs using nasopharyngeal samples s...
Additional file 2: of Identification of gene expression profiles in myocardial infarction: a systematic review and meta-analysis
PMIDs for each article and the excluding reasons. This file provides a detailed list of PMIDs for... more PMIDs for each article and the excluding reasons. This file provides a detailed list of PMIDs for the articles identified and the reasons for their exclusion. (TXT 3 kb)
Additional file 1: of Identification of gene expression profiles in myocardial infarction: a systematic review and meta-analysis
This file includes the Meta-analysis Prisma flowchart and the supplementary results regarding the... more This file includes the Meta-analysis Prisma flowchart and the supplementary results regarding the data analysis of the article. (DOCX 756 kb)
The human GPCR signal transduction network
Network Modeling Analysis in Health Informatics and Bioinformatics, 2021
The eukaryotic cell surface G protein-coupled receptors (GPCRs) interact with a wide spectrum of ... more The eukaryotic cell surface G protein-coupled receptors (GPCRs) interact with a wide spectrum of ligands. The intracellular transmission of the extracellular signal is mediated by the selective coupling of GPCRs to G proteins, which, in turn, activate downstream effectors. GPCRs are of paramount pharmacological importance, with approximately 40% of all commercial drugs targeting these proteins. Herein, we have made an effort to unravel the molecular mechanisms underlying the GPCR-mediated signaling pathway and the way this pathway is associated with diseases. Network-based approaches were utilized to delineate the GPCR pathway, incorporating data from gene expression profiles across eleven healthy tissues and disease–gene associations from three diverse resources. The associations between the tissue-specific expression profiles of the disease-related genes along with the relative risk of disease development were further investigated. In the GPCR-activated pathway, the signal was found to be amplified at the successive steps of the pathway so that the effector molecules are highly expressed compared to ligands. This amplification effect was more pronounced when the respective genes encoding the particular proteins were associated with diseases. It was also found that co-expressed genes, corresponding to interacting molecules in affected tissues, may constitute powerful predictive markers for disease development. A disease risk prediction model based on tissue-specific expression profiles of the disease-associated genes was also generated. These findings could be applied to clinical settings.
Association of ITPA gene polymorphisms with adverse effects of AZA/6-MP administration: a systematic review and meta-analysis
The Pharmacogenomics Journal, 2022
Azathioprine (AZA) and its metabolite, mercaptopurine (6-MP), are widely used immunosuppressant d... more Azathioprine (AZA) and its metabolite, mercaptopurine (6-MP), are widely used immunosuppressant drugs. Polymorphisms in genes implicated in AZA/6-MP metabolism, reportedly, could account in part for their potential toxicity. In the present study we performed a systematic review and a meta-analysis, comprising 30 studies and 3582 individuals, to investigate the putative genetic association of two inosine triphosphatase (ITPA) polymorphisms with adverse effects in patients treated with AZA/6-MP. We found that rs1127354 is associated with neutropenia in general populations and in children (OR: 2.39, 95%CI: 1.97–2.90, and OR: 2.43, 95%CI: 2.12–2.79, respectively), and with all adverse effects tested herein in adult populations (OR: 2.12, 95%CI: 1.22–3.69). We also found that rs7270101 is associated with neutropenia and leucopenia in all-ages populations (OR: 2.93, 95%CI: 2.36–3.63, and OR: 2.82, 95%CI: 1.76–4.50, respectively) and with all adverse effects tested herein in children (OR: 1.74, 95%CI: 1.06–2.87). Stratification according to background disease, in combination with multiple comparisons corrections, verified neutropenia to be associated with both polymorphisms, in acute lymphoblastic leukemia (ALL) patients. These findings suggest that ITPA polymorphisms could be used as predictive biomarkers for adverse effects of thiopurine drugs to eliminate intolerance in ALL patients and clarify dosing in patients with different ITPA variants.
Histone
methylation immediately adjacent to active
Multivariate Methods for Meta-Analysis of Genetic Association Studies
Methods in molecular biology, 2018
Multivariate meta-analysis of genetic association studies and genome-wide association studies has... more Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All ...
Η θυρεοειδής ορμόνη (Τ3) παίζει πολλαπλό και σημαντικό ρόλο στην ομοιόσταση, στην ανάπτυξη, στην ... more Η θυρεοειδής ορμόνη (Τ3) παίζει πολλαπλό και σημαντικό ρόλο στην ομοιόσταση, στην ανάπτυξη, στην μεταμόρφωση των αμφίβιων, στη διαφοροποίηση και στη νεοπλασία. Η δράση της Τ3 διενεργείται μέσω της σύνδεσής της με τον υποδοχέα θυρεοειδούς ορμόνης (TR), ο οποίος με τη σειρά του συνδέεται σε ειδικές αλληλουχίες DNA που ονομάζονται στοιχεία απόκρισης στη θυρεοειδή ορμόνη (TREs). Ο TR παρουσία Τ3 ενεργοποιεί τη μεταγραφή ενώ χωρίς ορμόνη ο TR την καταστέλλει χρησιμοποιώντας πληθώρα μηχανισμών. Η v-ErbΑ ογκοπρωτεϊνη είναι μια ιική μεταλλαγμένη παραλλαγή του TRα που κωδικοποιείται από τον ιό της ερυθροβλάστωσης των πτηνών (AEV). Η συνεργασία του v-erbA με το v-erbB, το δεύτερο ογκογονίδιο του AEV με δραστικότητα κινάσης τυροσίνης, οδηγεί σε ερυθρολευχαιμία ως αποτέλεσμα του ανεξέλεγκτου πολλαπλασιασμού και της παύσης της διαφοροποίησης. Λόγω μεταλλάξεων, το ν-erbΑ δεν μπορεί να δεσμεύσει Τ3 και έτσι δεν μπορεί να ενεργοποιήσει τη μεταγραφή, όπως το κυτταρικό ομόλογό του, ο TR. Η υπόθεση ότ...
SummaryBackgroundWith the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (CO... more SummaryBackgroundWith the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed.MethodsWe performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LF...
Meta-analysis of gene expression profiles in preeclampsia
Pregnancy Hypertension, 2020
OBJECTIVE Preeclampsia (PE) is a serious complication of pregnancy. It is considered a complex co... more OBJECTIVE Preeclampsia (PE) is a serious complication of pregnancy. It is considered a complex condition influenced by maternal genes, environmental factors and a deregulated immune response of the mother, but the etiology is largely unknown. The aim of this study is to identify differentially expressed genes (DEGs) in PE, to help elucidate the identification of the disease etiological mechanisms. STUDY DESIGN The databases Pubmed and GEO were searched according to PRISMA guidelines for the existence of gene expression data on placental samples from case-control studies. After meta-analysis the identified DEGs were further analyzed with STRING and PANTHER to retrieve interaction networks and overrepresented biochemical pathways. RESULTS Only 10 gene expression datasets and articles fulfilled inclusion criteria, containing data on 195 patients and 231 controls, and were analyzed. Meta-analysis identified 629 DEGs to be associated with PE at a False Discovery Rate p-value of 0.01. Network analysis showed few highly interconnected genes involved in innate immunity and signal transduction pathways indicative of a multifaceted disease with etiological heterogeneity. over representation analysis revealed that these genes participate mainly in carbohydrates, amino acids and pyrimidine metabolism, circadian clock system and signal transduction pathways. CONCLUSIONS This work, combining rigorous methods of meta-analysis and the use of modern bioinformatics tools, proposes the existence of novel, overlooked so far, biochemical pathways and mechanisms to contribute to PE development such as carbohydrate, aminoacids and pyrimidine metabolism. Our findings pave the way for further investigation of the above pathways in experimental efforts to decipher the orchestrating mechanisms for PE development.
Parasitology Research, 2019
Leishmaniases are cutaneous, mucocutaneous, and visceral diseases affecting humans and domesticat... more Leishmaniases are cutaneous, mucocutaneous, and visceral diseases affecting humans and domesticated animals mostly in the tropical and subtropical areas of the planet. Host genetics have been widely investigated for their role in developing various infectious diseases. The SLC11A1 gene has been reported to play a role in neutrophil function and is associated with susceptibility to infectious and inflammatory diseases such as tuberculosis or rheumatoid arthritis. In the present meta-analysis, we investigate the genetic association of SLC11A1 polymorphisms with susceptibility to leishmaniasis. Genotypes and other risk-related data were collected from 13 case-control and family-based studies (after literature search). Conventional random-effects meta-analysis was performed using STATA 13. To pool case-control and family-based data, the weighted Stouffer's method was also applied. Eight polymorphisms were investigated: rs2276631, rs3731865, rs3731864, rs17221959, rs201565523, rs2279015, rs17235409, and rs17235416. We found that rs17235409 (D543N) and rs17235416 (1729 + 55del4) are significantly associated with a risk for cutaneous leishmaniasis (CL), whereas rs17221959, rs2279015, and rs17235409 are associated with visceral leishmaniasis (VL). Our results suggest that polymorphisms in SLC11A1 affect susceptibility to CL and VL. These findings open new pathways in understanding macrophage response to Leishmania infection and the genetic factors predisposing to symptomatic CL or VL that can lead to the usage of predictive biomarkers in populations at risk.
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Papers by GEORGIA BRALIOU