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In Print: Feb 10, 2009


Journal: Bioinformatics. 2009 Jan 1;25(1):48-53.
Title: Power enhancement via multivariate outlier testing with gene expression arrays.
Authors: A Asare; Z Gao; V Carey; R Wang; V Seyfert-Margolis

Abstract: As the use of microarrays in human studies continues to increase, stringent quality assurance is necessary to ensure accurate experimental interpretation. In response to this issue, the authors present a "formal approach for microarray quality assessment that is based on dimension reduction of established measures of signal and noise components of expression followed by parametric multivariate outlier testing." The authors applied their approach to several data resources, and show that the "exclusion of arrays by this approach substantially increases inferential power, or the ability to detect differential expression, in large clinical studies."

Journal: Bioinformatics. 2009 Jan 15;25(2):281-3.
Title: The SNPMaP package for R: a framework for genome-wide association using DNA pooling on microarrays.
Authors: O Davis; R Plomin; L Schalkwyk

Abstract: "Large-scale genome-wide association studies using thousands of high-density SNP microarrays are an essential tool in the search for loci related to heritable variation in many phenotypes," the paper’s abstract states. "However, the cost of GWA remains beyond the reach of many researchers. Fortunately, the majority of statistical power can still be obtained by estimating allele frequencies from DNA pools, reducing the cost to that of tens, rather than thousands, of arrays." The authors present a set of software tools for processing SNP microarrays and pooling (SNPMaP) data from CEL files to Relative Allele Scores in the rich R statistical computing environment.

Journal: Biomacromolecules. 2009 Jan 21. [Epub ahead of print]
Title: Advanced substrate fabrication for cell microarrays
Authors: A Hook; H Thissen; N Voelcker.

Abstract: The authors present a technology for the "fabrication and characterization of chemical patterns using a technique that can be readily integrated with methods currently used for the formation of microarrays." According to the authors, a "high-density poly(ethylene glycol) coating was deposited on glass slides as a background exhibiting low cell attachment properties. Phenylazide modified polymers were then printed on this background. UV irradiation of these polymer arrays resulted in the cross-linking of the polymer spots and their covalent attachment to the surface. Cell attachment was shown to follow the resultant surface chemistry pattern." The authors used the method to create a transfected cell microarray, therefore "demonstrating not only the ability of this platform to limit cell attachment to specific regions, but the suitability for chip-based functional genomics, in particular, and high density cell assays in general."

Journal: Cancer Research. 2009 Jan 1;69(1):23-6.
Title: GEMS (Gene expression metasignatures), a web resource for querying meta-analysis of expression microarray datasets: 17β-Estradiol in MCF-7 cells.
Authors: S Ochsner; D Steffen; S Hilsenbeck; E Chen; C Watkins; N McKenna

Abstract: With large amounts of public expression microrray data being generated by multiple laboratories, it is a "significant task for the bench researcher to routinely identify available datasets, and then to evaluate the collective evidence across these datasets for regulation of a specific gene in a given system," according to the authors of this study. 17β-Estradiol stimulation of MCF-7 cells is a widely used model in the growth of breast cancer, though "myriad independent studies have profiled the global effects of this hormone on gene expression in these cells, disparate experimental variables and the limited power of the individual studies have combined to restrict the agreement between them as to the specific gene expression signature elicited by this hormone." To address these issues, the authors have developed a freely accessible Web resource, Gene Expression MetaSignatures that provides the user a "consensus for each gene in the system."

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Journal: Chemistry & Biology. 2009 Jan 30;16(1):36-47.
Title: Novel fluorescent glycan microarray strategy reveals ligands for galectins.
Authors: X Song; B Xia; S Stowell; Y Lasanajak; D Smith; R Cummings

Abstract: Galectin-1 and galectin-3 are widely expressed galectins with immunoregulatory functions in animals. To explore their glycan specificity, the authors developed microarrays of naturally occurring glycans using a "bifunctional fluorescent linker, 2-amino-N-(2-aminoethyl)-benzamide (AEAB), directly conjugated through its arylamine group by reductive amination to free glycans to form glycan-AEABs (GAEABs). Glycans from natural sources were used to prepare over 200 GAEABs, which were purified by multidimensional high-pressure liquid chromatography and covalently immobilized onto N-hydroxysuccinimide-activated glass slides via their free alkylamine." According to the authors, "fluorescence-based screening demonstrated that Gal-1 recognizes a wide variety of complex N-glycans, whereas Gal-3 primarily recognizes poly-N-acetyllactosamine-containing glycans independent of N-glycan presentation." The authors also argue that, "GAEABs provide a general solution to glycan microarray preparation from natural sources for defining the specificity of glycan-binding proteins."

Journal: Genes and Immunity. 2009 Jan;10(1):77-83.
Title: Genome-wide SNP-based linkage analysis of tuberculosis in Thais.
Authors: S Mahasirimongkol; H Yanai: N Nishida: C Ridruechai: I Matsushita; J Ohashi; S Summanapan; N Yamada; S Moolphate; C Chuchotaworn; A Chaiprasert; W Manosuthi; P Kantipong; S Kanitwittaya; T Sura; S Khusmith; K Tokunaga; P Sawanpanyalert; N Keicho

Abstract: To gain insight into host genetic factors associated with tuberculosis, nonparametric linkage analysis was performed using an Affymetrix SNP GeneChip array that included 59,860 bi-allelic markers, on samples from 93 Thai families with multiple siblings and 195 individuals affected with tuberculosis. The genotyping "revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate." The results imply "new evidence of genetic risk factors for tuberculosis in the Asian population," according to the paper’s abstract. The study also supports a "clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients."

Journal: Investigative Ophthalmology and Visual Science. 2009 Jan 17. [Epub ahead of print]
Title: Genomic profiling and identification of high-risk uveal melanoma by array-CGH analysis of primary tumors and liver metastases
Authors: J Trolet; P Hupe; I Huon; I Lebigot: C Decraene: O Delattre: X Sastre-Garau: S Saule: J Thiery: C Plancher; B Asselain: L Desjardins; P Mariani; S Piperno-Neumann; E Barillot; J Couturier

Abstract: Approximately 50 percent of uveal melanoma patients will develop incurable metastases. This study analyzed genomic profiles in a large series of ocular tumors and liver metastases, in order to design a genome-based classifier for metastatic risk assessment. Specifically, a set of 86 UM tumors and 66 liver metastases was analyzed using BAC CGH microarrays. A clustering was performed, and correlation with the metastatic status was sought among a subset of 71 patients with a minimum follow-up of 24 months. The status of chromosome 3 was further examined in tumors and metastases with disomy 3 were checked using Illumina SNP microarray technology. A prognostic classifier was constructed using a log-linear model on minimal regions and leave-one-out cross-validation. The paper concludes that the "analysis of the status of these specific chromosome regions by genome profiling on SNP microarrays should be a reliable tool for identifying high-risk patients in future adjuvant therapy protocols."

Journal: Human Mutations. 2009 Jan;30(1):115-22.
Title: Validation of microarray-based resequencing of 93 worldwide mitochondrial genomes
Authors: A Hartmann; M Thieme; L Nanduri; T Stempfl; C Moehle; T Kivisild: P Oefner

Abstract: Methods that allow the "rapid, inexpensive and accurate sequencing of mitochondrial DNA are of great interest," according to the paper’s abstract. The authors used the Affymetrix GeneChip Human Mitochondrial Resequencing Array 2.0 in a direct comparison of 93 worldwide mitochondrial genomes sequenced by both the MitoChip and dideoxy terminator sequencing. The project revealed an average call rate of 99.48 percent and an accuracy of > or =99.98 percent for the MitoChip. The performance was achieved by using in-house software for the automated analysis of additional probes on the array that cover the most common haplotypes in the hypervariable regions. "A major drawback of the MitoChip," the authors note, is its "inability to detect insertions/deletions and its low sensitivity and specificity in the detection of heteroplasmy." However, the "vast majority of haplogroup defining polymorphism in the mtDNA phylogeny could be called unambiguously and more rapidly than with conventional sequencing."

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Journal: The ISME Journal. 2009 Jan 8. [Epub ahead of print]
Title: Bacterial diversity and White Plague Disease-associated community changes in the Caribbean coral Montastraea faveolata
Authors: S Sunagawa; T Desantis; Y Piceno; E Brodie; M Desalvo; C Voolstra; E Weil; G Andersen; M Medina

Abstract: Increasing evidence confirms the crucial role bacteria and archaea play within the coral host and its associated microbial community. This study highlights the "limitation of 16S rRNA gene clone library sequencing as the sole method to comprehensively describe coral-associated communities." The limitation was addressed by combining a high-density 16S rRNA gene microarray with clone-library sequencing as to study bacterial communities in healthy versus diseased corals. Specifically, the authors determined an increase in diversity as well as a significant shift in community structure in Montastraea faveolata colonies displaying phenotypic signs of White Plague Disease type II.

Journal: Molecular Cancer. 2009, 8:5 (19 January 2009)
Title: A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis.
Authors: R Skotheim; G Thomassen; M Eken; G Lind; F Micci; F Ribeiro; N Cerveira; M Teixeira; S Heim; T Rognes; R Lothe

Abstract: The authors present an oligonucleotide microarray strategy where one can screen for "all known oncogenic fusion transcripts" in a single experiment. To accomplish this, the authors combined measurements of chimeric transcript junctions with exon-wise measurements of individual fusion partners. A DNA microarray containing 68,861 oligonucleotide probes that includes oligos covering "all combinations of chimeric exon-exon junctions from 275 pairs of fusion genes, as well as sets of oligos internal to all the exons of the fusion partners," was designed. Proof of principle was demonstrated by detection of known fusion genes from all six positive controls consisting of leukemia cell lines and prostate cancer biopsies.

Nucleic Acids Research. 2009 Jan;37(1):e7.
Title: A single molecule array for digital targeted molecular analyses.
Authors: J Göransson; C Wählby; M Isaksson; W Howell; J Jarvius; M Nilsson

Abstract: This paper presents a "random array format together with a decoding scheme for targeted multiplex digital molecular analyses. DNA samples are analyzed using multiplex sets of padlock or selector probes that create circular DNA molecules upon target recognition. The circularized DNA molecules are amplified through rolling-circle amplification to generate amplified single molecules. A random array is generated by immobilizing all ASMs on a microscopy glass slide. The ASMs are identified and counted through serial hybridizations of small sets of tag probes, according to a combinatorial decoding scheme." According to the paper’s abstract, this random array format permits "at least 10 iterations of hybridization, imaging and dehybridization, a process required for the combinatorial decoding scheme."

Journal: Nucleic Acids Research. 2009 Jan;37(1):e6.
Title: Array-based evolution of DNA aptamers allows modeling of an explicit sequence-fitness landscape.
Authors: C Knight; M Platt; W Rowe; D Wedge; F Khan; P Day; A McShea; J Knowles; D Kell

Abstract: Mapping the landscape of possible macromolecular polymer sequences to their fitness in performing biological functions is a challenge across the biosciences. A paradigm is the case of aptamers, nucleic acids that can be selected to bind particular target molecules. In this paper, the authors characterize the sequence-fitness landscape for aptamers binding allophycocyanin protein via a novel Closed Loop Aptameric Directed Evolution approach. The approach "reveals a complex sequence-fitness mapping, and hypotheses for the physical basis of aptameric binding; it also enables rapid design of novel aptamers with desired binding properties," according to the abstract.

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Journal: Physiologia Plantarum. 2009 Jan 7. [Epub ahead of print]
Title: Extraction and labeling methods for microarrays using small amounts of plant tissue.
Authors: A Stimpson; R Pereira; J Kiss; M Correll

Abstract: This paper describes procedures that were developed to maximize the yield of high-quality RNA from small amounts of plant biomass for microarrays. Two disruption techniques, bead milling and pestle and mortar, were compared for the yield and the quality of RNA extracted from 1-week-old Arabidopsis thaliana seedlings. The pestle and mortar method of extraction showed "enhanced RNA quality at the smaller biomass samples compared with the bead milling technique." A method of low-quantity RNA labeling for microarrays was used on five 7-day-old seedlings, and microarray analyses were performed on a small plant sample using these methods and compared with extractions performed with larger biomass samples. The relative expression levels of selected genes were confirmed with quantitative real-time polymerase chain reaction, suggesting that these methods can be used for "plant experiments where the biomass is extremely limited."

Journal: PLoS ONE. 2009;4(1):e4128. Epub 2009 Jan 6.
Title: Using pathway signatures as means of identifying similarities among microarray experiments.
Authors: L Beltrame; L Rizzetto; R Paola; P Rocca-Serra; L Gambineri; C Battaglia; D Cavalieri

Abstract: Approaches using a defined group of genes, such as pathways and cellular networks have been proposed to improve the interpretation of microarray experiments. The authors propose a method to compare microarray experiments at the pathway level by first, generating pathway signatures, described as a "set of descriptors recapitulating the biologically meaningful pathways related to some clinical/biological variable of interest"; and second, using these signatures to interrogate microarray databases. The authors claim the method "successfully groups together similar samples, independently of the experimental design."

Journal: Proceedings of the National Academy of Sciences. 2009 Jan 30. [Epub ahead of print]
Title: Large-scale detection of ubiquitination substrates using cell extracts and protein microarrays.
Authors: Y Merbl; M Kirschner

Abstract: Identification of protein targets of post-translational modification is an important analytical problem in biology, and protein microarrays exposed to cellular extracts could offer a rapid and convenient means of identifying modified proteins, dependent on a faithful reconstruction of in vivo conditions. The authors of this paper used "extracts that replicate the mitotic checkpoint and anaphase release to identify differentially regulated polyubiquitination. Protein microarrays were exposed to these complex extracts, and the polyubiquitinated products were detected by specific antibodies," according to the abstract. The yield of potential anaphase-promoting complex substrates from the assay with concentrated cell extracts "suggests that combining microarray analysis of the products of post-translational modifications with extracts that preserve the physiological state of the cell can yield information on protein modification under various in vivo conditions."

The Scan

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Suicidal Ideation-Linked Loci Identified Using Million Veteran Program Data

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