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Search Results: 1 - 10 of 325568 matches for " Antigone S. Dimas "
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Candidate Causal Regulatory Effects by Integration of Expression QTLs with Complex Trait Genetic Associations
Alexandra C. Nica,Stephen B. Montgomery,Antigone S. Dimas,Barbara E. Stranger,Claude Beazley,Inês Barroso,Emmanouil T. Dermitzakis
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000895
Abstract: The recent success of genome-wide association studies (GWAS) is now followed by the challenge to determine how the reported susceptibility variants mediate complex traits and diseases. Expression quantitative trait loci (eQTLs) have been implicated in disease associations through overlaps between eQTLs and GWAS signals. However, the abundance of eQTLs and the strong correlation structure (LD) in the genome make it likely that some of these overlaps are coincidental and not driven by the same functional variants. In the present study, we propose an empirical methodology, which we call Regulatory Trait Concordance (RTC) that accounts for local LD structure and integrates eQTLs and GWAS results in order to reveal the subset of association signals that are due to cis eQTLs. We simulate genomic regions of various LD patterns with both a single or two causal variants and show that our score outperforms SNP correlation metrics, be they statistical (r2) or historical (D'). Following the observation of a significant abundance of regulatory signals among currently published GWAS loci, we apply our method with the goal to prioritize relevant genes for each of the respective complex traits. We detect several potential disease-causing regulatory effects, with a strong enrichment for immunity-related conditions, consistent with the nature of the cell line tested (LCLs). Furthermore, we present an extension of the method in trans, where interrogating the whole genome for downstream effects of the disease variant can be informative regarding its unknown primary biological effect. We conclude that integrating cellular phenotype associations with organismal complex traits will facilitate the biological interpretation of the genetic effects on these traits.
Data analysis issues for allele-specific expression using Illumina's GoldenGate assay
Matthew E Ritchie, Matthew S Forrest, Antigone S Dimas, Caroline Daelemans, Emmanouil T Dermitzakis, Panagiotis Deloukas, Simon Tavaré
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-280
Abstract: We analyze data from a mixture experiment where genomic DNA samples from pairs of individuals of known genotypes are pooled to create allelic imbalances at varying levels for the majority of SNPs on the array. We observe that GoldenGate has less sensitivity at detecting subtle allelic imbalances (around 1.3 fold) compared to extreme imbalances, and note the benefit of applying local background correction to the data. Analysis of data from a dye-swap control experiment allowed us to quantify dye-bias, which can be reduced considerably by careful normalization. The need to filter the data before carrying out further downstream analysis to remove non-responding probes, which show either weak, or non-specific signal for each allele, was also demonstrated. Throughout this paper, we find that a linear model analysis of the data from each SNP is a flexible modelling strategy that allows for testing of allelic imbalances in each sample when replicate hybridizations are available.Our analysis shows that local background correction carried out by Illumina's software, together with quantile normalization of the red and green channels within each array, provides optimal performance in terms of false positive rates. In addition, we strongly encourage intensity-based filtering to remove SNPs which only measure non-specific signal. We anticipate that a similar analysis strategy will prove useful when quantifying ASE on Illumina's higher density Infinium BeadChips.Preferential expression of one of the two alleles of a gene has been widely studied in the context of development, where key mechanisms such as genomic imprinting and X-inactivation lead to extreme allelic imbalances [1]. Allele-specific expression has been linked to the susceptibility of many human diseases [2-4].Various experimental techniques exist for measuring ASE [5], including microarray-based approaches that have been used in a number of studies to screen for ASE in a high-throughput manner [6-11]. With microarray
Modifier Effects between Regulatory and Protein-Coding Variation
Antigone S. Dimas,Barbara E. Stranger,Claude Beazley,Robert D. Finn,Catherine E. Ingle,Matthew S. Forrest,Matthew E. Ritchie,Panos Deloukas,Simon Tavaré,Emmanouil T. Dermitzakis
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000244
Abstract: Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.
Rheumatoid Arthritis of the Temporomandibular Joint; Comparison of Digital Panoramic Radiographs Taken Using the Joint Limitation Program [JLA View] and CT Scans  [PDF]
Antigone Delantoni
Open Journal of Rheumatology and Autoimmune Diseases (OJRA) , 2012, DOI: 10.4236/ojra.2012.23012
Abstract: Objective: The aim of this study was to evaluate the efficacy of digital panoramic radiographs using the JLA view pro-gram in cases of rheumatoid arthritis and compare them to CT scans of the patients. Methods: 40 patients with known condition of RA and clinical symptoms in the TMJ were selected for the study. Radiological evaluation included a panoramic radiograph of the TMJs that was taken and a computer tomography of the joints. In the panoramic radio-graphs taken, isolation of the TMJs was done using the JLA view program, while in the CT scans of the patients, all scans were taken with closed mouth, with a distance of 0.5 mm per slice. The parameters examined were: 1) Bony changes of the condyle; 2) The position of the condyle in the mandibular fossa; 3) The joint space; 4) Bony changes of mandibular fossa. Results: There were no statistically significant differences found between the two observers or be-tween the two joints of the same patient [right and left] on the panoramic radiographs. For the case of CT scans there were significant differences between the joint space of right and left joints, while in the ANOVA performed differences were found for the evaluation of the bony changes of the condyle. Conclusion: There were no significant differences between the two radiographic methods selected and therefore when a proper simple radiograph is taken and well evalu-ated, the conclusions drawn from it are well based and there is no need for further examinations
Patterns of Cis Regulatory Variation in Diverse Human Populations
Barbara E. Stranger equal contributor,Stephen B. Montgomery equal contributor,Antigone S. Dimas equal contributor,Leopold Parts,Oliver Stegle,Catherine E. Ingle,Magda Sekowska,George Davey Smith,David Evans,Maria Gutierrez-Arcelus,Alkes Price,Towfique Raj,James Nisbett,Alexandra C. Nica,Claude Beazley,Richard Durbin,Panos Deloukas,Emmanouil T. Dermitzakis
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002639
Abstract: The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs) after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations.
Group Classification and Conservation Laws for a two-dimensional Generalized Kuramoto-Sivashinsky Equation
S. Dimas,Y. Bozhkov
Mathematics , 2012, DOI: 10.1016/j.na.2013.02.010
Abstract: The two-dimensional anisotropic Kuramoto-Sivashinsky equation is a forth-order nonlinear evolution equation in two spatial dimensions that arises in sputter erosion and epitaxial growth on vicinal surfaces. A generalization of this equation is proposed and studied via group analysis methods. The complete group classification of this generalized Kuramoto-Sivashinsky equation is carried out, it is classified according to the property of the self-adjointness and the corresponding conservation laws are established.
Enhanced group analysis of a semi-linear general bond-pricing equation
Y. Bozhkov,S. Dimas
Mathematics , 2014,
Abstract: The enhanced group classification of a semi-linear generalization of a general bond-pricing equation is carried out by employing the underlying equivalence and additional equivalence transformations. The knowledge of the sub classes with larger Lie algebras than the general case enable us to find non trivial invariant solutions under the terminal and the barrier option condition.
Group Classification of a generalization of the Heath Equation
Y. Bozhkov,S. Dimas
Mathematics , 2013, DOI: 10.1016/j.amc.2014.05.100
Abstract: The complete group classification of a generalization of the Heath model is carried out by connecting it to the heat equation with nonlinear source. Examples of invariant solutions are given under the terminal and the barrier option condition.
Effects of psycho-educational training and stimulant medication on visual perceptual skills in children with attention deficit hyperactivity disorder
Antigone S Papavasiliou,Irene Nikaina,Ioanna Rizou,Stratos Alexandrou
Neuropsychiatric Disease and Treatment , 2007,
Abstract: Antigone S Papavasiliou, Irene Nikaina, Ioanna Rizou, Stratos AlexandrouDepartment of Neurology, Pendeli Children’s Hospital, Athens, GreeceAbstract: Attention deficit hyperactivity disorder (ADHD) is treated with stimulants and psycho-educational remedial programs despite limited literature support for the latter. This study aimed to examine changes in a “Test of Visual Perceptual Skills” (TVPS) that has not been previously reported in children with ADHD enrolled in such a program.Methods: Sixteen children, 7–11 years old, with ADHD were involved in occupational therapy and special education geared towards attention training. Six months later methylphenidate 1 mg/kg/day was prescribed. It was not taken by eight children because of family choice. The TVPS was given twice, upon diagnosis, and 8 months post-intervention. The groups were compared by a repeated measures analysis of variance (ANOVA) with medication as a between groups factor and test-retest scores as within factor.Results: All children demonstrated increases in total scores in the second measurement. Medicated children scored higher but ANOVA showed a nonsignificant F for the two groups, medicated and unmedicated (F = 0.0031, p = 0.9563), indicating a non-differential effect of the two levels of treatment. It revealed a significant F for the pre- and post-treatment total TVPS scores (F = 30.91, p < 0.0001) indicating a significant difference between pre- and post-treatment tests. The interaction between pre-post treatment and level of treatment (medicated–unmedicated) was nonsignificant (F = 2.20, p = 0.1604).Conclusion: TVPS scores improved in all children following intervention. Medicated children did better, but differences were nonsignificant.Keywords: ADHD, stimulants, psycho-educational therapy, TVPS
The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study
Alexandra C. Nica,Leopold Parts,Daniel Glass,James Nisbet,Amy Barrett,Magdalena Sekowska,Mary Travers,Simon Potter,Elin Grundberg,Kerrin Small,?sa K. Hedman,Veronique Bataille,Jordana Tzenova Bell,Gabriela Surdulescu,Antigone S. Dimas,Catherine Ingle,Frank O. Nestle,Paola di Meglio,Josine L. Min,Alicja Wilk,Christopher J. Hammond,Neelam Hassanali,Tsun-Po Yang,Stephen B. Montgomery,Steve O'Rahilly,Cecilia M. Lindgren,Krina T. Zondervan,Nicole Soranzo,Inês Barroso,Richard Durbin,Kourosh Ahmadi,Panos Deloukas ,Mark I. McCarthy ,Emmanouil T. Dermitzakis ,Timothy D. Spector ,The MuTHER Consortium
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002003
Abstract: While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis—MCTA) permits immediate replication of eQTLs using co-twins (93%–98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%–20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.
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