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zCall: a rare variant caller for array-based genotyping

BIOINFORMATICS 2012年第19期28卷 2543-2545页

作者： Goldstein, Jacqueline I. Crenshaw, Andrew Carey, Jason Grant, George B. Maguire, Jared Fromer, Menachem O'Dushlaine, Colm Moran, Jennifer L. Chambert, Kimberly Stevens, Christine Sklar, Pamela Hultman, Christina M. Purcell, Shaun McCarroll, Steven A. Sullivan, Patrick F. Daly, Mark J. Neale, Benjamin M. Massachusetts Gen Hosp Dept Med Analyt & Translat Genet Unit Boston MA 02114 USA Harvard Univ Sch Med Boston MA 02114 USA Broad Inst MIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA Mt Sinai Sch Med Dept Psychiat Div Psychiat Genom New York NY 10029 USA Broad Inst MIT & Harvard Stanley Ctr Psychiat Res Cambridge MA 02142 USA Karolinska Inst Dept Med Epidemiol & Biostat Stockholm Sweden Harvard Univ Sch Med Dept Genet Boston MA 02115 USA Univ N Carolina Chapel Hill Sch Med Dept Genet Chapel Hill NC 27514 USA

zCall is a variant caller specifically designed for calling rare single-nucleotide polymorphisms from array-based technology. This caller is implemented as a post-processing step after a default calling algorithm has been applied. The algorithm uses the intensity profile of the common allele homozygote cluster to define the location of the other two genotype clusters. We demonstrate improved detection of rare alleles when applying zCall to samples that have both Illumina Infinium HumanExome BeadChip and exome sequencing data available.

关键词： microarray technology GENOTYPE-environment interaction SINGLE nucleotide polymorphisms GENETIC algorithms ZYGOTES ALLELES

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A Soluble α-Dithienotetrathiafulvalene Derivative for Organic Field-effect Transistors

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CHEMISTRY LETTERS 2012年第4期41卷 435-437页

作者： Doi, Iori Goshome, Kiyotaka Miyazaki, Eigo Takimiya, Kazuo Hiroshima Univ Fac Engn Dept Appl Chem Hiroshima 7398527 Japan

Bis(octylthio) derivative of alpha-dithienotetrathiafulvalene (alpha-DT-TTF) was synthesized, characterized, and examined as a semiconductor for organic field-effect transistors (OFETs). In contrast to no field-effect responses of devices based on evaporated thin-film of the parent alpha-DT-TTF, the octylthio derivative afforded solution-processed OFETs showing apparent normally-on behaviors with field-effect mobility of up to 0.6 cm(2)V(-1)s(-1). Characterization of the thin-film revealed that the octylthio groups had significant impact on self-assembly, affording high quality thin films with well-oriented molecular array.

关键词： microarray technology FIELD EFFECT MOBILITY thin films Semiconductor materials Organic field-effect transistors

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Expression of Genes Associated with H Factor in Fibroblasts Infected with Borrelia Spirochaetes

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SCANDINAVIAN JOURNAL OF IMMUNOLOGY 2012年第4期76卷 354-358页

作者： Geca, A. Gola, J. Dudek, S. Jasik, K. Muc-Wierzgon, M. Nowakowska-Zajdel, E. Niedworok, E. Mazurek, U. Silesian Med Univ Dept Internal Dis PL-41902 Bytom Poland Silesian Med Univ Dept Mol Biol PL-41902 Bytom Poland Silesian Med Univ Dept Microbiol PL-41902 Bytom Poland Silesian Med Univ Dept Human Nutr PL-41902 Bytom Poland

Infection with Borrelia spirochaetes leads to the launch of specific and non-specific immunological response in humans. Activation of the complement system is one of the first defence mechanisms against penetrating pathogens. The aim of this study was to select genes related to the alternative pathway of the complement system [including complement factor H (CFH)], differentiating the type of infection in the system model, that is, a culture of normal human diploid fibroblasts infected with three different spirochaete genospecies: Borrelia afzelii, Borrelia garinii and Borrelia burgdorferii sensu stricto, by comparing the infected fibroblast culture with the control fibroblast one. With the use of oligonucleotide microarrays HGU-133A, the differences in the expression of genes selected on the basis of a scientific database Affymetrix were studied by comparing transcriptomes from the four cultures of fibroblasts. In the result of infection of fibroblast cultivation with a specific Borrelia genospecies, a variable expression of certain CFH and complement system-associated genes, specific for one genospecies only, B. afzelii C1QBP, CD59, C2, CD46 and FHL1;B. garinii C1S and CLU;Borrelia burgeforii CFB, A2M and VSIG4, was observed. CFH differentiates infections induced by B. afzelii and B. garinii from infections induced by B. burgdorferii sensu stricto.

关键词： GENE expression FIBROBLASTS BORRELIA diseases IMMUNE response COMPLEMENT factor H SPIROCHETES microarray technology

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Global changes in gene expression of grapefruit peel tissue in response to the yeast biocontrol agent Metschnikowia fructicola

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MOLECULAR PLANT PATHOLOGY 2012年第4期13卷 338-349页

作者： Hershkovitz, Vera Ben-Dayan, Clarita Raphael, Ginat Pasmanik-Chor, Metsada Liu, Jia Belausov, Eduard Aly, Radi Wisniewski, Michael Droby, Samir Agr Res Org Dept Postharvest Sci Volcani Ctr IL-50250 Bet Dagan Israel Hebrew Univ Jerusalem Robert H Smith Fac Agr Food & Environm IL-76100 Rehovot Israel Tel Aviv Univ Bioinformat Unit Fac Life Sci IL-69978 Tel Aviv Israel ARS USDA Appalachian Fruit Res Stn Kearneysville WV 25430 USA

To gain a better understanding of the molecular changes taking place in citrus fruit tissue following the application of the yeast biocontrol agent Metschnikowia fructicola, microarray analysis was performed on grapefruit surface wounds using an Affymetrix Citrus GeneChip. Using a cut-off of P < 0.05 and a 1.5-fold change difference as biologically significant, the data indicated that 1007 putative unigenes showed significant expression changes following wounding and yeast application relative to wounded controls. microarray results of selected genes were validated by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The data indicated that yeast application induced the expression of the genes encoding Respiratory burst oxidase (Rbo), mitogen-activated protein kinase (MAPK) and mitogen-activated protein kinase kinase (MAPKK), G-proteins, chitinase (CHI), phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS) and 4-coumarate-CoA ligase (4CL). In contrast, three genes, peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT), were down-regulated in grapefruit peel tissue treated with yeast cells. Moreover, suppression was correlated with significantly higher levels of hydrogen peroxide, superoxide anion and hydroxyl radical production in yeast-treated surface wounds. Interestingly, large amounts of hydrogen peroxide were detected inside yeast cells recovered from wounded fruit tissue, indicating the ability of the yeast to activate reactive oxygen species when it is in contact with plant tissue. This study provides the first global picture of gene expression changes in grapefruit in response to the yeast antagonist M. fructicola.

关键词： GRAPEFRUIT GENE expression in plants PLANT diseases BIOLOGICAL pest control agents microarray technology REVERSE transcriptase polymerase chain reaction MITOGEN-activated protein kinase kinase

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In-depth Characterization via Complementing Culture-Independent Approaches of the Microbial Community in an Acidic Hot Spring of the Colombian Andes

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MICROBIAL ECOLOGY 2012年第1期63卷 103-115页

作者： Bohorquez, Laura C. Delgado-Serrano, Luisa Lopez, Gina Osorio-Forero, Cesar Klepac-Ceraj, Vanja Kolter, Roberto Junca, Howard Baena, Sandra Mercedes Zambrano, Maria Corp CorpoGen Mol Genet & Biotechnol Bogota 110231 DC Colombia Colombian Ctr Genom & Bioinformat Extreme Environ Bogota 110231 DC Colombia Pontificia Univ Javeriana Dept Biol Unidad Saneamiento & Biotecnol Ambiental Bogota DC Colombia Harvard Univ Sch Med Boston MA 02115 USA

The microbial community of a Colombian high mountain hot spring, El Coquito, was analyzed using three different culture-independent assessments of 16S ribosomal RNA genes: clone libraries, pyrosequencing of the V5-V6 hypervariable region, and microarray. This acidic spring had a diverse community composed mainly of Bacteria that shared characteristics with those from other hot springs and extreme acidic environments. The microbial community was dominated by Proteobacteria, Firmicutes, and Planctomycetes and contained chemotrophic bacteria potentially involved in cycling of ferrous and sulfur-containing minerals and phototrophic organisms, most of which were eukaryotic micro-algae. Despite the presence of a large proportion of novel, unclassified sequences, the taxonomic profiles obtained with each strategy showed similarities at higher taxonomic levels. However, some groups, such as Spirochaetes and Aquificae, were identified using only one methodology, and more taxa were detected with the gene array, which also shared more groups with the pyrosequencing data. Overall, the combined use of different approaches provided a broader view of the microbial community in this acidic hot spring.

关键词： MICROBIAL ecology microarray technology RIBOSOMAL RNA -- Molecular structure PROTEOBACTERIA PHOTOSYNTHETIC bacteria SPIROCHETES MICROBIAL genetics

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Perturbation of nuclear lamin A causes cell death in chondrocytes

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ARTHRITIS AND RHEUMATISM 2012年第6期64卷 1940-1949页

作者： Attur, Mukundan Ben-Artzi, Ami Yang, Qing Al-Mussawir, Hayf E. Worman, Howard J. Palmer, Glyn Abramson, Steven B. New York Univ Hosp Joint Dis Dept Pathol & Med Div Rheumatol New York NY 10003 USA NYU Sch Med New York NY 10003 USA Columbia Univ New York NY USA

Objective Mutations in LMNA encoding the A-type lamins cause several diseases, including those with features of premature aging and skeletal abnormalities. The aim of this study was to examine the expression of lamin A in cartilage from patients with osteoarthritis (OA) and the effects of its overexpression on chondrocyte senescence and apoptosis. Methods Human chondrocyte-like cells (SW-1353) were used. RNA isolated from human OA and non-OA cartilage was used for profiling messenger RNA expression, using Affymetrix microarray analysis. The effects of lamin A overexpression on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, and cytochrome c release, and with a TUNEL assay. Western blotting was performed to determine protein expression. Results Lamin A expression was markedly elevated in OA cartilage samples compared with non-OA control samples. Western blot analysis confirmed increased expression of lamin A in OA compared with non-OA cartilage. Interleukin-1 beta treatment inhibited lamin A accumulation, whereas treatment with prostaglandin E2 (PGE2) caused a marked increase in lamin A accumulation. These effects of exogenous PGE2 on lamin A expression were mediated via the EP2/EP4 receptors. Transfected chondrocytes that expressed lamin A displayed markers of early senescence/apoptosis. Conclusion The results of this study suggest that lamin A is up-regulated in OA chondrocytes, and that increased nuclear accumulation of lamin A in response to catabolic stress may account for the premature aging phenotype and apoptosis of OA chondrocytes.

关键词： CARTILAGE physiology AGING APOPTOSIS BIOPSY ENZYME-linked immunosorbent assay MUTATION (Biology) OSTEOARTHRITIS POLYMERASE chain reaction FINANCING of research T-test (Statistics) WESTERN immunoblotting EQUIPMENT & supplies REVERSE transcriptase polymerase chain reaction DATA analysis software microarray technology

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Bayesian model-based clustering of temporal gene expression using autoregressive panel data approach

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BIOINFORMATICS 2012年第15期28卷 2004-2007页

作者： Nascimento, Moyses Safadi, Thelma Fonseca e Silva, Fabyano Nascimento, Ana Carolina C. Univ Fed Vicosa Dept Estat BR-36570000 Vicosa MG Brazil Univ Fed Lavras Dept Ciencias Exatas BR-37200000 Lavras MG Brazil

Motivation: In a microarray time series analysis, due to the large number of genes evaluated, the first step toward understanding the complex time network is the clustering of genes that share similar expression patterns over time. Up until now, the proposed methods do not point simultaneously to the temporal autocorrelation of the gene expression and the model-based clustering. We present a Bayesian method that considers jointly the fit of autoregressive panel data models and hierarchical gene clustering. Results: The proposed methodology was able to cluster genes that share similar expression over time, which was determined jointly by the estimates of autoregression parameters, by the average level of expression) and by the quality of the fitted model.

关键词： BAYESIAN analysis MATHEMATICAL models CLUSTER analysis (Statistics) GENE expression AUTOREGRESSIVE processes PANEL analysis DATA analysis microarray technology

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fRMA ST: frozen robust multiarray analysis for Affymetrix Exon and Gene ST arrays

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BIOINFORMATICS 2012年第23期28卷 3153-3154页

作者： McCall, Matthew N. Jaffee, Harris A. Irizarry, Rafael A. Univ Rochester Med Ctr Dept Biostat & Computat Biol Rochester NY 14642 USA Johns Hopkins Univ Dept Biostat Baltimore MD 21205 USA

Frozen robust multiarray analysis (fRMA) is a single-array preprocessing algorithm that retains the advantages of multiarray algorithms and removes certain batch effects by downweighting probes that have high between-batch residual variance. Here, we extend the fRMA algorithm to two new microarray platforms-Affymetrix Human Exon and Gene 1.0 ST-by modifying the fRMA probe-level model and extending the frma package to work with oligo ExonFeatureSet and GeneFeatureSet objects.

关键词： microarray technology ROBUST control GENETICS ALGORITHMS ANALYSIS of variance

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VegaMC: a R/bioconductor package for fast downstream analysis of large array comparative genomic hybridization datasets

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BIOINFORMATICS 2012年第19期28卷 2512-2514页

作者： Morganella, Sandro Ceccarelli, Michele Univ Sannio Dept Sci I-82100 Benevento Italy BIOGEM Scarl Bioinformat CORE Contrada Camporeale I-83031 Ariano Irpino Italy

Identification of genetic alterations of tumor cells has become a common method to detect the genes involved in development and progression of cancer. In order to detect driver genes, several samples need to be simultaneously analyzed. The Cancer Genome Atlas (TCGA) project provides access to a large amount of data for several cancer types. TGCA is an invaluable source of information, but analysis of this huge dataset possess important computational problems in terms of memory and execution times. Here, we present a R/ package, called VegaMC (Vega multi- channel), that enables fast and efficient detection of significant recurrent copy number alterations in very large datasets. VegaMC is integrated with the output of the common tools that convert allele signal intensities in log R ratio and B allele frequency. It also enables the detection of loss of heterozigosity and provides in output two web pages allowing a rapid and easy navigation of the aberrant genes. Synthetic data and real datasets are used for quantitative and qualitative evaluation purposes. In particular, we demonstrate the ability of VegaMC on two large TGCA datasets: colon adenocarcinoma and glioblastoma multiforme. For both the datasets, we provide the list of aberrant genes which contain previously validated genes and can be used as basis for further investigations.

关键词： CANCER genetics microarray technology GENOMICS CANCER cells COMPARATIVE studies GLIOBLASTOMA multiforme ADENOCARCINOMA

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optiCall: a robust genotype-calling algorithm for rare, low-frequency and common variants

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BIOINFORMATICS 2012年第12期28卷 1598-1603页

作者： Shah, T. S. Liu, J. Z. Floyd, J. A. B. Morris, J. A. Wirth, N. Barrett, J. C. Anderson, C. A. Wellcome Trust Sanger Inst Hinxton CB10 1SA Cambs England

Motivation: Existing microarray genotype-calling algorithms adopt either SNP-by-SNP (SNP-wise) or sample-by-sample (sample-wise) approaches to calling. We have developed a novel genotype-calling algorithm for the Illumina platform, optiCall, that uses both SNP-wise and sample-wise calling to more accurately ascertain genotypes at rare, low-frequency and common variants. Results: Using data from 4537 individuals from the 1958 British Birth Cohort genotyped on the Immunochip, we estimate the proportion of SNPs lost to downstream analysis due to false quality control failures, and rare variants misclassified as monomorphic, is only 1.38% with optiCall, in comparison to 3.87, 7.85 and 4.09% for Illuminus, GenoSNP and GenCall, respectively. We show that optiCall accurately captures rare variants and can correctly account for SNPs where probe intensity clouds are shifted from their expected positions.

关键词： ALGORITHMS ROBUST control GENETICS microarray technology SINGLE nucleotide polymorphisms BIOINFORMATICS

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