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Search Results: 1 - 10 of 347831 matches for " Sündüz Kele? "
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Normalization of ChIP-seq data with control
Liang Kun,KeleSündüz
BMC Bioinformatics , 2012, DOI: 10.1186/1471-2105-13-199
Abstract: Background ChIP-seq has become an important tool for identifying genome-wide protein-DNA interactions, including transcription factor binding and histone modifications. In ChIP-seq experiments, ChIP samples are usually coupled with their matching control samples. Proper normalization between the ChIP and control samples is an essential aspect of ChIP-seq data analysis. Results We have developed a novel method for estimating the normalization factor between the ChIP and the control samples. Our method, named as NCIS (Normalization of ChIP-seq) can accommodate both low and high sequencing depth datasets. We compare statistical properties of NCIS against existing methods in a set of diverse simulation settings, where NCIS enjoys the best estimation precision. In addition, we illustrate the impact of the normalization factor in FDR control and show that NCIS leads to more power among methods that control FDR at nominal levels. Conclusion Our results indicate that the proper normalization between the ChIP and control samples is an important step in ChIP-seq analysis in terms of power and error rate control. Our proposed method shows excellent statistical properties and is useful in the full range of ChIP-seq applications, especially with deeply sequenced data.
dPeak: High Resolution Identification of Transcription Factor Binding Sites from PET and SET ChIP-Seq Data
Dongjun Chung,Dan Park,Kevin Myers,Jeffrey Grass,Patricia Kiley,Robert Landick,Sündüz Kele
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1003246
Abstract: Chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) has been successfully used for genome-wide profiling of transcription factor binding sites, histone modifications, and nucleosome occupancy in many model organisms and humans. Because the compact genomes of prokaryotes harbor many binding sites separated by only few base pairs, applications of ChIP-Seq in this domain have not reached their full potential. Applications in prokaryotic genomes are further hampered by the fact that well studied data analysis methods for ChIP-Seq do not result in a resolution required for deciphering the locations of nearby binding events. We generated single-end tag (SET) and paired-end tag (PET) ChIP-Seq data for factor in Escherichia coli (E. coli). Direct comparison of these datasets revealed that although PET assay enables higher resolution identification of binding events, standard ChIP-Seq analysis methods are not equipped to utilize PET-specific features of the data. To address this problem, we developed dPeak as a high resolution binding site identification (deconvolution) algorithm. dPeak implements a probabilistic model that accurately describes ChIP-Seq data generation process for both the SET and PET assays. For SET data, dPeak outperforms or performs comparably to the state-of-the-art high-resolution ChIP-Seq peak deconvolution algorithms such as PICS, GPS, and GEM. When coupled with PET data, dPeak significantly outperforms SET-based analysis with any of the current state-of-the-art methods. Experimental validations of a subset of dPeak predictions from PET ChIP-Seq data indicate that dPeak can estimate locations of binding events with as high as to resolution. Applications of dPeak to ChIP-Seq data in E. coli under aerobic and anaerobic conditions reveal closely located promoters that are differentially occupied and further illustrate the importance of high resolution analysis of ChIP-Seq data.
Multiple tests of association with biological annotation metadata
Sandrine Dudoit,Sündüz Kele,Mark J. van der Laan
Statistics , 2008, DOI: 10.1214/193940307000000446
Abstract: We propose a general and formal statistical framework for multiple tests of association between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The known gene-annotation profiles, corresponding to the fixed features of the genome, may concern Gene Ontology (GO) annotation, pathway membership, regulation by particular transcription factors, nucleotide sequences, or protein sequences. The unknown gene-parameter profiles, corresponding to the variable features of the genome, may be, for example, regression coefficients relating possibly censored biological and clinical outcomes to genome-wide transcript levels, DNA copy numbers, and other covariates. A generic question of great interest in current genomic research regards the detection of associations between biological annotation metadata and genome-wide expression measures. This biological question may be translated as the test of multiple hypotheses concerning association measures between gene-annotation profiles and gene-parameter profiles. A general and rigorous formulation of the statistical inference question allows us to apply the multiple hypothesis testing methodology developed in [Multiple Testing Procedures with Applications to Genomics (2008) Springer, New York] and related articles, to control a broad class of Type I error rates, defined as generalized tail probabilities and expected values for arbitrary functions of the numbers of Type I errors and rejected hypotheses. The resampling-based single-step and stepwise multiple testing procedures of [Multiple Testing Procedures with Applications to Genomics (2008) Springer, New York] take into account the joint distribution of the test statistics and provide Type I error control in testing problems involving general data generating distributions (with arbitrary dependence structures among variables), null hypotheses, and test statistics.
Discovering Transcription Factor Binding Sites in Highly Repetitive Regions of Genomes with Multi-Read Analysis of ChIP-Seq Data
Dongjun Chung,Pei Fen Kuan,Bo Li,Rajendran Sanalkumar,Kun Liang,Emery H. Bresnick,Colin Dewey,Sündüz Kele
PLOS Computational Biology , 2011, DOI: 10.1371/journal.pcbi.1002111
Abstract: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is rapidly replacing chromatin immunoprecipitation combined with genome-wide tiling array analysis (ChIP-chip) as the preferred approach for mapping transcription-factor binding sites and chromatin modifications. The state of the art for analyzing ChIP-seq data relies on using only reads that map uniquely to a relevant reference genome (uni-reads). This can lead to the omission of up to 30% of alignable reads. We describe a general approach for utilizing reads that map to multiple locations on the reference genome (multi-reads). Our approach is based on allocating multi-reads as fractional counts using a weighted alignment scheme. Using human STAT1 and mouse GATA1 ChIP-seq datasets, we illustrate that incorporation of multi-reads significantly increases sequencing depths, leads to detection of novel peaks that are not otherwise identifiable with uni-reads, and improves detection of peaks in mappable regions. We investigate various genome-wide characteristics of peaks detected only by utilization of multi-reads via computational experiments. Overall, peaks from multi-read analysis have similar characteristics to peaks that are identified by uni-reads except that the majority of them reside in segmental duplications. We further validate a number of GATA1 multi-read only peaks by independent quantitative real-time ChIP analysis and identify novel target genes of GATA1. These computational and experimental results establish that multi-reads can be of critical importance for studying transcription factor binding in highly repetitive regions of genomes with ChIP-seq experiments.
Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding
Kevin S. Myers,Huihuang Yan,Irene M. Ong,Dongjun Chung,Kun Liang,Frances Tran,Sündüz Kele,Robert Landick ,Patricia J. Kiley
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003565
Abstract: FNR is a well-studied global regulator of anaerobiosis, which is widely conserved across bacteria. Despite the importance of FNR and anaerobiosis in microbial lifestyles, the factors that influence its function on a genome-wide scale are poorly understood. Here, we report a functional genomic analysis of FNR action. We find that FNR occupancy at many target sites is strongly influenced by nucleoid-associated proteins (NAPs) that restrict access to many FNR binding sites. At a genome-wide level, only a subset of predicted FNR binding sites were bound under anaerobic fermentative conditions and many appeared to be masked by the NAPs H-NS, IHF and Fis. Similar assays in cells lacking H-NS and its paralog StpA showed increased FNR occupancy at sites bound by H-NS in WT strains, indicating that large regions of the genome are not readily accessible for FNR binding. Genome accessibility may also explain our finding that genome-wide FNR occupancy did not correlate with the match to consensus at binding sites, suggesting that significant variation in ChIP signal was attributable to cross-linking or immunoprecipitation efficiency rather than differences in binding affinities for FNR sites. Correlation of FNR ChIP-seq peaks with transcriptomic data showed that less than half of the FNR-regulated operons could be attributed to direct FNR binding. Conversely, FNR bound some promoters without regulating expression presumably requiring changes in activity of condition-specific transcription factors. Such combinatorial regulation may allow Escherichia coli to respond rapidly to environmental changes and confer an ecological advantage in the anaerobic but nutrient-fluctuating environment of the mammalian gut.
Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis
Amber J. Marty?,Aimee T. Broman?,Robert Zarnowski?,Teigan G. Dwyer?,Laura M. Bond?,Anissa Lounes-Hadj Sahraoui?,Jo?l Fontaine?,James M. Ntambi?,Sündüz Kele??,Christina Kendziorski
PLOS Pathogens , 2015, DOI: 10.1371/journal.ppat.1004959
Abstract: In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0–48 hours), gene expression microarrays were used to compare SREB? to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.
Pour une typologie moderne des dictionnaires
Sündüz ?ztürk Kasar
Synergies Turquie , 2008,
Abstract: Le présent article se propose de faire une typologie moderne des dictionnaires, car la pratique lexicographique ne cesse de se renouveler avec les progrès récents dans les domaines de l’informatique et de la lexicologie. Une classification moderne de dictionnaires pourrait être fondée sur six critères : le mode de présentation ; le matériau de la microstructure ; le nombre et le statut des langue(s) étudiée(s) ; les propriétés des informations fournies ; l’extension de la nomenclature et l’organisation de la macrostructure. Suivant ces six critères, nous distinguons, respectivement, les dictionnaires de divers types : dictionnaires sur papier/dictionnaires électroniques/dictionnaires numériques ; dictionnaires (proprement dits)/dictionnaires illustrés/dictionnaires en images ; dictionnaires monolingues/dictionnaires plurilingues ; dictionnaires de mots ou dictionnaires de langue/dictionnaires de choses ou dictionnaires encyclopédiques ; dictionnaires extensifs/dictionnaires restrictifs et, dernièrement, dictionnaires alphabétiques/dictionnaires thématiques. Nous essayons d’illustrer cette typologie par un tableau qui contient des exemples pour chaque type de dictionnaire.
The Ancient Egyptian Hieroglyphic Language Was Created by Sumerian Turks  [PDF]
Metin Gündüz
Advances in Anthropology (AA) , 2017, DOI: 10.4236/aa.2017.74013
Abstract: The “phonetic sound value of each and every hieroglyphic picture’s expressed and intended meaning as a verb or as a noun by the creators of the ancient Egyptian hieroglyphic picture symbols, exactly matches’, the same meaning” as well as the “first letter of the corresponding meaning of the Turkish word’s first syllablewith the currently spoken dialects of the Turkish language. The exact intended sound value as well as the meaning of hieroglyphic pictures as nouns or verbs is individually and clearly expressed in the original?hieroglyphic pictures. This includes the 30 hieroglyphic pictures of?well-known consonants as well as some vowel sounds-of the language of the ancient Egyptians. There is no exception to this rule. Statistical and probabilistic certainty beyond any reasonable doubt proves the Turkish language connection. The hieroglyphic pictures match with 2 variables (the phonetic value and intended meaning). 1) Each hieroglyphic picture’s known phonetic value through the Coptic language was proven by Champollion in 1822 (Champollion (1836), Robinson (2013)) who had well-known and unchallenged expertise in the Coptic language. 2) The phonetic value of each and every hieroglyphic picture matches with the corresponding meaning of the Turkish word’s
Esterase variation in Turkish white-toothed shrews (Crocidura): Record of a trimeric esterase
Tez C.,?zcan S.,ndüz ?.,Haskili? ?.
Archives of Biological Sciences , 2009, DOI: 10.2298/abs0904719t
Abstract: This study focuses on esterase variation of the genus Crocidura in Turkey. A total of 248 white-toothed shrews were analyzed by means of cellulose acetate gel electrophoresis. Liver tissue and alfa naphthyl acetate were used to investigate esterase variation in Turkish white-toothed shrews. A different esterase banding pattern was found in one Crocidura individual. This phenotype had four anodally migrated bands on cellulose acetate gel. The Crocidura individual displaying the given phenotype was identified as Crocidura suaveolens. The different esterase banding pattern observed in this study is considered to be a result of the trimeric structure of esterase in the lesser white-toothed shrew (Crocidura suaveolens).
Investigation of relationship between the D-dimer and ischemia-modified albumin levels with the radiological imaging-based pulmonary embolism severity score in acute pulmonary embolism
Süleyman Türedi,Süleyman Caner Karahan,Ahmet Mente?e,Abdülkadir Gündüz
Anadolu Kardiyoloji Dergisi , 2010,
Abstract: Objective: To investigate possible relationship between the D-dimer and ischemia-modified albumin (IMA) levels and radiological imaging-based severity scores in pulmonary embolism (PE) based on two different radiological characteristics; the pulmonary arterial obstruction index (PAOI) and the right ventricle/left ventricle (RV/LV) ratio. Methods: In this prospective cohort study, forty-seven patients presenting to the emergency department and definitively diagnosed with PE using spiral computerized tomography (CT) were initially enrolled in the study. Levels of IMA and D-dimer were assessed colorimetrical and immuno-turbidimetric methods, respectively. The PAOI and RV/LV ratios were calculated from CT images. The levels of biochemical parameters between the groups were compared with use of Mann-Whitney U and Kruskal-Wallis tests and relationship between the radiological scores were assessed using the Spearman correlation test.Results: Analysis of the calculated PAOI and RV/LV ratio revealed a significant correlation between them (r=0.36, p=0.023). D-dimer levels differed considerably among the mild (<40%), moderate (40%-60%) and severe (60%) groups constituted on the basis of PAOI (p=0.039). This difference stemmed from those in D-dimer levels in the mild group, PAOI <40 % and the severe group, PAOI 60% (p=0.02; Z= -2.328). In addition, D-dimer levels and PAOI revealed a positive correlation, but no similar correlation was determined between D-dimer levels and RV/LV. There were no significant correlations between IMA and D-dimer levels, PAOI and RV/LV ratios.Conclusion: In the biochemical determination of severity of PE based on radiological characteristics, D-dimer may be a more relevant marker than IMA, which has been proposed as a new marker.
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