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In Print: Jun 8, 2010


Microarray Papers of Note Published May 2010

Journal: American Journal of Human Genetics. 2010 May 14;86(5):749-64.

Title: Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.

Authors: Miller D, et al.

The International Standard Cytogenomic Array Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by chromosomal microarray. In this paper, they provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. They found that CMA offers a "much higher diagnostic yield" for genetic testing, but that "truly balanced rearrangements and low-level mosaicism" are still generally not detectable by arrays. The ISCA recommends that CMA be used in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for most patients. BioArray News interviewed co-author David Ledbetter about the recommendation last month (BAN 5/18/2010).

Journal: Analytical Biochemistry. 2010 May 1;400(1):10-8.

Title: Development of miniaturized immunoassay: influence of surface chemistry and comparison with enzyme-linked immunosorbent assay and Western blot.

Authors: El Khoury G, et al.

In this study, two surface chemistries for protein microarrays and immunofluorescent assays were developed. Glass slides were functionalized with N-hydroxysuccinimide ester via a monofunctional silane or maleic anhydride-alt-methyl vinyl ether copolymer to allow covalent grafting of histone proteins. Analytical performance of these microarrays was then evaluated for the detection of anti-histone autoantibodies present in the sera of patients suffering from a systemic autoimmune disease, namely systemic lupus erythematosus, and the results were compared with those of an enzyme-linked immunosorbent assay and Western blot. The authors found the detection limit of their MAMVE copolymer microarrays was 50-fold lower than that of the ELISA. Furthermore, 100-fold less volume of biological samples was required with their immunoassays.

Journal: Analytical Chemistry. 2010 May 1;82(9):3848-55.

Title: Addressable nanowell arrays formed using reversibly sealable hybrid elastomer-metal stencils.

Authors: Pla-Roca M, et al.

The authors present an addressable nanoliter-well plate with micrometer sized wells. The nanowells are formed by reversibly sealing a steel stencil featuring an array of micrometer-scale openings to an optically transparent substrate. A soft polymer is patterned photolithographically around each opening to form a microgasket for pressure sensitive, liquid tight, and reversible sealing to any type of smooth substrate, either hydrophilic or hydrophobic. The stencils are used to pattern cells, make protein microarrays, and create nanowells on surfaces to study reverse transfection by first spotting plasmids encoding fluorescent proteins into the wells, seeding cells, and monitoring the transfection of the cells in real time using time-lapse imaging.

Journal: Biotechnology & Bioengineering. 2010 May 1;106(1):106-18.

Title: Three-dimensional cell culture microarray for high-throughput studies of stem cell fate.

Authors: Fernandes T, et al.

The authors developed a three-dimensional cellular microarray platform to track stem cell fate and quantification of specific stem cell markers. The platform consists of a miniaturized 3D cell culture array on a functionalized glass slide for spatially addressable high-throughput screening. A microarray spotter was used to deposit cells onto a modified glass surface to yield an array consisting of cells encapsulated in alginate gel spots. A method based on an immunofluorescence technique scaled down to function on a cellular microarray was also used to quantify specific cell marker protein levels in situ. According to the authors, the platform is suitable for studying the expansion of mouse embryonic stem cells as they retain their pluripotent and undifferentiated state.

Journal: Biotechnology Journal. 2010 May;5(5):463-9.

Title: On-chip cell culture on a microarray of extracellular matrix with surface modification of poly(dimethylsiloxane).

Authors: Hattori K, et al.

The authors report surface modification of a poly(dimethylsiloxane) substrate with a microarray of extracellular matrix for on-chip cell culture. The ECM proteins collagen and fibronectin were covalently immobilized on an 8 cm x 8 cm microarray format by micropatterned UV-induced graft polymerization through a photomask and dehydration-condensation reaction through a microfabricated stencil. Identical spots of ECMs were formed and the geometry of the spots corresponded to the micropattern of the photomask and stencil. The authors demonstrated the culture of CHO-K1 cells on the ECM microarray chip, and found that cells proliferated on the fibronectin spots during a two-day culture.

Journal: Clinical Chemistry. 2010 May;56(5):805-13.

Title: Aneuploidy detection in mixed DNA samples by methylation-sensitive amplification and microarray analysis.

Authors: Brown L, et al.

The authors developed a method for methylation-sensitive amplification of DNA suitable for use with cell-free, fetal nucleic acid samples. They used this method with two-color microarray analysis with a custom-made array to investigate whether relative amplification, and relative methylation, could be evaluated for a large number of genomic loci. They found that microarray assessment of genomic methylation accurately predicted the degree of methylation measured with bisulfite-conversion PCR and confirmed that DNA from first-trimester trophoblast was generally hypomethylated compared with whole-blood DNA.

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Journal: Clinical Genetics. 2010 May 8. [Epub ahead of print]

Title: High-resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting.

Authors: Wincent J, et al.

The authors evaluated the usefulness of high-resolution arrays as a diagnostic tool in their laboratory and investigated the diagnostic yield in the first 160 patients who were clinically referred for investigation of developmental delay. During this period both 38,000-BAC arrays and 244,000-probe oligonucleotide arrays were used. Copy-number variations not previously reported as normal variants were detected in 22.5 percent of cases. In 13.1 percent, the aberrations were considered causal to the phenotype and in 9.4 percent the clinical significance was uncertain. The authors found that increasing the resolution of a whole-genome screen in the diagnostic setting has a "drawback of detecting an increased number of CNVs with uncertain contribution to a phenotype." Still, they recommended array-CGH as the first-step analysis in the genetic evaluation of patients with developmental delay.

Journal: European Journal of Human Genetics. 2010 May 12. [Epub ahead of print]

Title: Genomic profile of copy number variants on the short arm of human chromosome 8.

Authors: Yu S, et al.

The authors evaluated 966 consecutive pediatric patients with various developmental disorders by high-resolution microarray-based comparative genomic hybridization and found 10 individuals with pathogenic copy number variants on the short arm of chromosome 8, representing approximately 1 percent of the patients analyzed. Two patients with 8p terminal deletion associated with interstitial inverted duplication had different mechanisms leading to the formation of a dicentric intermediate during meiosis. Three probands carried an identical approximately 5.0 megabase interstitial duplication of chromosome 8p23.1. Other CNVs with deletion- or duplication-specific start or stop coordinates on 8p provided "useful information for exploring the basic mechanisms of complex structural rearrangements in the human genome."

Journal: Genome Biology. 2010 May 19;11(5):R52. [Epub ahead of print]

Title: Towards a comprehensive structural variation map of an individual human genome.

Authors: Pang A, et al.

The authors of this study combined computational re-analysis of existing whole genome sequence data with microarray-based analysis to detect 12,178 structural variants covering 40.6 megabases that were not reported in the initial sequencing of the first published personal genome. Based on these results, they estimate a total non-SNP variation content of 48.8Mb in a single genome. They also state that a "large number of SVs have been unreported in the individual genomes published to date."

Journal: Genomics. 2010 May 6. [Epub ahead of print]

Title: Comparative gene expression analysis in mouse models for multiple sclerosis, Alzheimer's disease and stroke for identifying commonly regulated and disease-specific gene changes.

Authors: Tseveleki V, et al.

The authors analyzed global gene expression in brain from mouse models representing three major central nervous system disorders, cerebral stroke, multiple sclerosis, and Alzheimer's disease, and compared the results to normal brain using DNA microarray expression profiling. A comparison of dysregulated genes across disease models revealed common genes and pathways, including key components of estrogen and TGF-beta signaling pathways that have been associated with neuroprotection as well as a neurodegeneration mediator, TRPM7. Additionally, for each disease model, the authors discovered collections of differentially expressed genes that provide "insight into the individual pathology and its associated mechanisms."

Journal: Journal of Agricultural Food Chemistry. 2010 May 26;58(10):6018-26.

Title: An event-specific DNA microarray to identify genetically modified organisms in processed foods.

Authors: Kim J, et al.

The authors developed an event-specific DNA microarray system to identify 19 genetically modified organisms, including two GM soybeans, thirteen GM maizes, three GM canolas, and one GM cotton. The microarray included 27 oligonucleotide probes optimized to identify endogenous reference targets, event-specific targets, screening targets, and an internal target. Thirty-seven maize-containing food products purchased from South Korean and US markets were tested for the presence of GM maize using this microarray system. Thirteen GM maize events were simultaneously detected using multiplex PCR coupled with microarray on a single chip, at a limit of detection of approximately 0.5 percent. The authors detected GM maize in 11 of the 37 food samples tested, and suggest that an event-specific DNA microarray system can detect GMOs in processed foods.

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Journal: Journal of Clinical Oncology. 2010 May 1;28(13):2198-206.

Title: Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.

Authors: Barry W, et al.

The authors investigated the additional impact of intratumor heterogeneity on the performance of several microarray-based assays in breast cancer. Genome-wide expression profiling was performed on 50 core needle biopsies from 18 breast cancer patients using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Global profiles of expression were characterized using unsupervised clustering methods and variance components models. Array-based measures of estrogen receptor and progesterone receptor status were compared with immunohistochemistry. The precision of genomic predictors of ER pathway status, recurrence risk, and sensitivity to chemotherapeutics was evaluated by interclass correlation. The authors found that intratumor heterogeneity, although present at the level of individual gene expression, does not preclude precise microarray-based predictions of tumor behavior or clinical outcome in breast cancer patients.

Journal: Journal of Microbiology Methods. 2010 May;81(2):127-34.

Title: Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: effective recovery of bacterial and archaeal DNA using mechanical cell lysis.

Authors: Salonen A, et al.

The authors of this study compared four widely used fecal DNA extraction methods, and found their DNA yields to vary up to 35-fold. Bacterial, archaeal and human DNA was quantified by real-time PCR, and a compositional analysis of different extracts was carried out using the Human Intestinal Tract Chip, a 16S rRNA gene-based phylogenetic microarray. The authors determined that the overall microbiota composition was highly similar between the methods in contrast to the profound differences between the subjects. A detailed comparative analysis of mechanical and enzymatic methods showed that, despite their overall similarity, the mechanical cell disruption by repeated bead beating showed the highest bacterial diversity and resulted in significantly improved DNA extraction efficiency of archaea and some bacteria. By applying the mechanical disruption method, a high prevalence of methanogenic archaea was detected in healthy subjects, exceeding the typical values reported previously.

Journal: Journal of Microbiology Methods. 2010 May;81(2):96-100.

Title: An oligonucleotide microarray to characterize multidrug resistant plasmids.

Authors: Lindsey R, et al.

The aim of this study was to design a microarray with oligonucleotide probes for every gene in the six Inc A/C and one Inc H1 plasmids of interest while representing all redundant sequences in Enterobacteriaceae only once. The microarray is printed in triplicate with 493 unique oligonucleotide probes 70 nucleotides in length. Salmonella enterica and Escherichia coli control strains and test plasmids were hybridized to the plasmid microarray. According to the authors, the hybridization presents a "rapid and cost effective method" for high-density screening of isolates to evaluate the gene content of Inc A/C and H1 plasmids and shows "how plasmids can change content with transmission."

Journal of Pediatrics. 2010 May;156(5):810-7, 817.e1-817.e4.

Title: Array comparative genomic hybridization as a diagnostic tool for syndromic heart defects.

Authors: Breckpot J, et al.

The aim of this study was to investigate different aspects of the introduction of array comparative genomic hybridization in clinical practice. Using arrays, the authors analyzed 150 patients with a syndromic congenital heart defect of unknown cause at 1 megabase resolution. Twenty-nine of these patients with normal results underwent re-analysis with a 244,000-probe oligonucleotide microarray. With a logistic regression model, the authors assessed the predictive value of patient characteristics for causal imbalance detection and constructed an algorithm to evaluate the causality of copy number variants. The authors found 75 variants not listed as clinically neutral polymorphisms, two of which were considered to be causal.

Journal: Journal of Proteome Research. 2010 May 7;9(5):2565-72.

Title: Identification of cell surface glycoprotein markers for glioblastoma-derived stem-like cells using a lectin microarray and LC-MS/MS approach.

Authors: He J, et al.

The authors used a method combining lectin microarray and laser capture-mass spectrometry/mass spectrometry to discover the cell surface glycoprotein markers of a glioblastoma-derived stem-like cell line. Lectin microarray analysis of cell surface glycans showed that two galactose-specific lectins — trichosanthes kirilowii agglutinin and peanut agglutinin — could distinguish the stem-like glioblastoma neurosphere culture from a traditional adherent glioblastoma cell line. Agarose-bound TKA and PNA were used to capture the glycoproteins from the two cell cultures, which were then analyzed by LC-MS/MS. The glycoproteins were quantified by spectral counting, resulting in the identification of 12 and 11 potential glycoprotein markers from the TKA and PNA captured fractions, respectively. Almost all of these proteins were membrane proteins. Differential expression was verified by Western blotting analysis of six interesting proteins. According to the authors, an improved understanding of these proteins may be important for earlier diagnosis and better therapeutic targeting of glioblastoma.

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Journal: Microbiology. 2010 May 6. [Epub ahead of print]

Title: Identification of non-coding RNAs in environmental vibrios.

Authors: Silveira A, et al.

In this study, the authors explore non-coding RNA diversity in four recently sequenced environmental Vibrio species (V. alginolyticus 40B, V. communis 1DA3, V. mimicus VM573 and V. campbellii BAA-1116) by performing in silico searches using Infernal and Rfam for the identification of 38 putative ncRNA encoding genes. They chose to experimentally validate the identifications for V. campbellii BAA-1116 using a microarray-based expression profiling strategy. Transcript hybridization to tiled probes targeting annotated V. campbellii BAA-1116 intergenic regions revealed that 21 of the 38 predicted ncRNA genes were expressed in mid-log phase cultures grown in nutrient rich media. The microarray findings were confirmed by testing a subset of three highly expressed and three moderately expressed ncRNAs via reverse transcription PCR.

Journal: Molecular Human Reproduction. 2010 May 19. [Epub ahead of print]

Title: SNP microarray based 24 chromosome aneuploidy screening is significantly more consistent than FISH.

Authors: Treff N, et al.

The authors investigated the prevalence of chromosomal abnormality and mosaicism found with two different single-cell aneuploidy screening techniques. Thirteen arrested cleavage stage embryos were studied, each biopsied into individual cells. The cells from each embryo were randomized into two groups. Those destined for fluorescence in situ hybridization-based aneuploidy screening were fixed, 1 cell per slide. Cells for SNP microarray based aneuploidy screening were put into individual tubes. The authors determined that microarray was "significantly more reliable" than FISH for providing an interpretable result. Still, different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was "significantly less commonly observed" by microarray than by FISH. Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed "significantly more unique genetic diagnoses" per embryo than microarray.

Journal: Nature Biotechnology. 2010 May 31;27(2):149-55.

Title: A flexible and fully integrated system for amplification, detection and genotyping of genomic DNA targets based on microfluidic oligonucleotide arrays.

Authors: Summerer D, et al.

The authors describe a strategy allowing for amplification, detection and genotyping of different genomic DNA targets in a single reaction container that makes use of primer-directed solution-phase amplification with integrated labeling in a closed, microfluidic oligonucleotide array. Selective array probes allow for subsequent detection and genotyping of generated amplicons by hybridization. The described array contains up to 15,624 programmable features that can be designed, de novo synthesized, and tested within 24 hours using an automated benchtop microarray synthesizer. The system was evaluated by amplifying and detecting different loci of viral, bacterial, and eukaryotic genomes.

Journal: Neurology. 2010 May 18;74(20):1583-90.

Title: Tourette syndrome is associated with recurrent exonic copy number variants.

Authors: Sundaram S, et al.

The authors performed a genome-wide screening of SNP genotyping microarray data to identify recurrent or de novo rare exonic copy number variants in a case-control association study of patients with Tourette syndrome. They identified 5 exon-affecting rare CNVs that are either de novo or recurrent in 10 out of 111 patients with TS but were not found in 73 ethnically matched controls or in the entries of the Database of Genomic Variants. Three out of the 5 CNVs were implicated previously by other studies in schizophrenia, autism, and attention-deficit hyperactivity disorder, leading the authors to suggest that these CNVs produce a continuum of neuropsychiatric disturbances that manifest in different ways depending on other genetic, environmental, or stochastic factors.

Journal: Nucleic Acids Research. 2010 May;38(9):e111.

Title: Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays.

Authors: Lee C, et al.

The authors have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components, and mutation hotspots. The authors also describe accompanying base-calling software, EvolSTAR, relies on neighborhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries.

Journal: RNA. 2010 May;16(5):991-1006.

Title: Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression.

Authors: Git A, et al.

The authors of this study sought to compare the relative performance of microarrays and next-generation sequencing with regards to microRNA analysis. They analyzed three biological samples across six miRNA microarray platforms and compared their hybridization performance. The authors then examined the ability of the platforms, as well as NGS, to detect differentially expressed miRNAs. The results were validated for 89 miRNAs by RT-PCR. They authors also designed a new method to evaluate false-positive and false-negative rates for all methods in the absence of a reference method.

The Scan

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Researchers from the UK and Italy have tested a gene drive for mosquitoes to limit the spread of malaria, NPR reports.

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Prion Pause to Investigate

Science reports that a moratorium on prion research has been imposed at French public research institutions.

Genome Research Papers on Gut Microbe Antibiotic Response, Single-Cell RNA-Seq Clues to Metabolism, More

In Genome Research this week: gut microbial response to antibiotic treatment, approach to gauge metabolic features from single-cell RNA sequencing, and more.