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In Print: Microarray Papers of Note

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Microarray Papers of Note Published July and August 2011

Journal: The American Journal of Surgical Pathology. 2011 Jul;35(7):1030-7.

Title: Evaluation of a gene expression microarray-based assay to determine tissue type of origin on a diverse set of 49 malignancies.

Authors: Beck A, et al.

The goal of this study was to evaluate the performance of Pathwork Diagnostics' Tissue of Origin Frozen assay on a collection of malignancies. The authors classified 49 cases into one of four groups: common morphology from a tissue type included in the assay, uncommon morphology from a tissue type included in the assay, tumor from a tissue type not included in the assay, and malignancies of unknown primary. They found "strong diagnostic performance" for common morphologies from tissue types on the assay, but reported a "significant decline in performance" for uncommon morphologies from tissue types included in the assay, cases with an indeterminate result, cases with an incorrect prediction, and for tumors from tissue types not included in the assay. For the seven malignancies of unknown primary in the study set, the assay provided a likely clinically useful result in only two of seven cases, the authors wrote.


Journal: Analytical and Bioanalytical Chemistry. 2011 Jul;400(9):3005-11.

Title: Imaging surface plasmon resonance for multiplex microassay sensing of mycotoxins.

Authors: Dorokhin D, et al.

A microarray of mycotoxin-protein conjugates was fabricated using a continuous flow microspotter device. A competitive inhibition immunoassay format was developed for the simultaneous detection of deoxynivalenol and zearalenone. The assay results agreed with liquid chromatography-mass spectrometry data. The immunoassay meets European Union regulatory specifications and could be used for mycotoxin analysis in food and feed samples, according to the authors.


Journal: Biochemistry. 2011 Aug 15. [Epub ahead of print]

Title: Isoenergetic microarrays to study the structure and interactions of DsrA and OxyS RNAs in two- and three-component complexes.

Authors: Fratczak A, et al.

Isoenergetic microarrays were used to study the binding of RNA to protein or other RNAs as well as the interactions of two different RNAs and protein in a three-component complex. The RNAs used as models were the regulatory DsrA and OxyS RNAs from Escherichia coli, the fragments of their target mRNAs, and their complexes with Hfq protein. The collected results showed the advantages and some limitations of microarray mapping, according to the authors.


Journal: Chemical Research in Toxicology. 2011 Aug 23. [Epub ahead of print]

Title: Comparing next-generation sequencing and microarray technologies in a toxicological study of the effects of aristolochic acid on rat kidneys.

Authors: Su Z, et al.

A toxicogenomics study design was used to compare the performance of an RNA-seq approach, using the Illumina Genome Analyzer II, to a microarray-based approach, using Affymetrix Rat Genome 230 2.0 arrays, for detecting differentially expressed genes in the kidneys of rats treated with aristolochic acid, a carcinogenic and nephrotoxic chemical most notably used for weight loss. The authors studied the comparability of the RNA-seq and microarray data in terms of absolute gene expression, gene expression patterns, differentially expressed genes, and biological interpretation. They found that RNA-seq was more sensitive in detecting genes with low expression levels, while similar gene expression patterns were observed for both platforms.


Journal: Genetics in Medicine. 2011 Jul;13(7):680-5

Title: American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants.

Authors: Kearney H, et al.

To assist clinical laboratories in the evaluation of copy number variants and to promote consistency in interpretation and reporting of genomic microarray results, the American College of Medical Genetics developed professional guidelines for the interpretation and reporting of copy number variation. The guidelines, found in this paper, apply primarily to evaluation of constitutional copy number variants detected in the postnatal setting.

BioArray News spoke with the authors of the paper last month (BAN 7/19/2011)

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Journal: Genetics in Medicine. 2011 Jul;13(7):676-9.

Title: American College of Medical Genetics recommendations for the design and performance expectations for clinical genomic copy number microarrays intended for use in the postnatal setting for detection of constitutional abnormalities.

Authors: Kearney H, et al.

In the paper, the American College of Medicine suggests that microarray platforms used by clinical cytogeneticists be evaluated and manufacturers regulated for the ability to accurately measure copy number gains or losses in DNA and that the subsequent interpretation of the findings and assignment of clinical significance be determined by medical professionals with appropriate training and certification. The paper contains specific recommendations for the design and performance expectations for clinical genomic copy number microarrays and associated software intended for use in the postnatal setting for detection of constitutional abnormalities.

BioArray News spoke with the authors of the paper last month (BAN 7/19/2011)


Journal: Human Molecular Genetics. 2011 Aug 15;20(16):3188-97.

Title: Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes.

Authors: Nakabayashi K, et al.

The authors analyzed rare reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotype for imprinted differentially methylated regions, or DMRs, using the Illumina Infinium methylation27 BeadChip microarray. The approach identified 15 imprinted DMRs associated with characterized imprinted domains, and confirmed the maternal methylation of the RB1 DMR. In addition, the authors discovered two new DMRs.


Journal: Human Mutation. 2011 Aug 17. [Epub ahead of print]

Title: Extending the scope of diagnostic chromosome analysis: detection of single gene defects using high resolution SNP-microarrays.

Authors: Bruno D, et al.

The authors describe 14 examples of single gene disorders caused by intragenic changes from a consecutive set of 6,500 tests using high-resolution SNP microarrays. The cases illustrate the increased scope of cytogenetic testing beyond dominant chromosome rearrangements that typically contain many genes. Nine of the cases confirmed the clinical diagnosis, followed a phenotype-to-genotype approach. Five were diagnosed by the laboratory analysis in the absence of a specific clinical diagnosis and two were clinically significant, incidental findings.


Journal: Journal of Animal Science. 2011 Aug 19. [Epub ahead of print]

Title: Microarray analysis reveals genes and functional networks relevant to the predisposition for inverted teats in pigs.

Authors: Chomwisarutkun K, et al.

The inverted teat defect is characterized by the failure of teats to protrude from the udder surface and has a negative impact on the economical efficiency of pig production, according to the authors. In this study, they compared the mRNA expression of teat tissues from non-affected pigs and affected pigs using microarrays. The authors screened 24,123 probe sets, of which 15,000 were analyzed for differential expression between mesenchymal and epithelial tissue of three categories of teats, normal teats of non-affected and affected animals, and inverted teats of the latter. Differential expression was more pronounced in epithelial than mesenchymal tissue and the comparisons among the three categories of teat showed that local processes at the site of the teat as well as processes taking place on the level of the organ contribute to the defect.


Journal: Journal of Immunological Methods. 2011 Aug 31;371(1-2):81-90.

Title: Screening and characterization of new monoclonal anti-benzo[a]pyrene antibodies using automated flow-through microarray technology.

Authors: Karsunke X, et al.

Mice were immunized with B[a]P-bovine serum albumin conjugates and 110 generated hybridoma cell lines screened by different techniques to identify clones that produce anti-B[a]P antibodies. Subsequently, an automated flow-through biochip noncompetitive direct chemiluminescence immunoassay was compared with conventional indirect and direct enzyme-linked immunosorbent assays. Six high-affinity monoclonal antibodies with different cross-reactivities for individual polycyclic aromatic hydrocarbons were identified by the chip-based assay and indirect microtiter plate ELISA. In comparison, the direct ELISA in the microtiter plate failed to identify three of these clones.


Journal: Lab on a Chip. 2011 Jul 21;11(14):2333-42.

Title: Dielectrophoresis-based cellular microarray chip for anticancer drug screening in perfusion microenvironments.

Authors: Hsiung L, et al.

The authors present a dielectrophoresis-based cellular microarray chip for cell-based anticancer drug screening in perfusion microenvironments. Human breast cancer cells, MCF7, were seeded into the chip and patterned via DEP forces onto the planar interdigitated ring electrode arrays. Results of cell patterning show substantial uniformity of patterned cells. The authors believe the chip could enable applications where cells are of limited supply, and supplement microfluidic perfusion cultures for clinical practices.

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Journal: Molecular & Cellular Proteomics. 2011 Aug;10(8):M111.010462. Epub 2011 May 12.

Title:Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis.

Authors: Kaller M, et al.

The authors combined pulsed stable isotope labeling with amino acids in cell culture, or pSILAC, and microarray analyses to identify miR-34a-induced changes in protein and mRNA expression. SILAC allowed the authors to quantify the de novo protein synthesis of 1,206 proteins after activation of a conditional miR-34a allele in a colorectal cancer cell line. About 19 percent of the detected proteins were differentially regulated, with 113 proteins being down-regulated and 115 up-regulated.


Journal: Molecular Reproduction and Development. 2011 Jul 19. [Epub ahead of print]

Title: Combining resources to obtain a comprehensive survey of the bovine embryo transcriptome through deep sequencing and microarrays.

Authors: Robert C, et al.

In an effort to obtain a comprehensive survey of the bovine embryo transcriptome and how it is modified by assisted reproductive technologies, the authors designed an embryo-specific microarray. Close to a million high-quality reads were produced from subtracted bovine embryo libraries using Roche 454 deep sequencing, enabling the creation of an augmented bovine genome catalog. The catalog was enriched with bovine embryo transcripts, and included newly discovered indel type and 3' UTR variants. The authors used this augmented bovine genome catalog to design the 42,000-probe EmbryoGene Bovine Microarray, which they claim is able to detect physiologically relevant changes in gene expression.


Journal: Nature. 2011 Aug 10;476(7359):214-9.

Title: Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Authors: Sawcer S, et al.

The researchers conducted an association study involving 9,772 individuals of European descent with multiple sclerosis who were recruited in 15 countries by 23 research teams participating in the International Multiple Sclerosis Genetics Consortium. The 17,376 unaffected control samples, also from individuals with European ancestry, came from the Wellcome Trust Case Control Consortium 2 control set. Study participants were genotyped using the Illumina Human 660-Quad and Illumina 1.2 M platforms. The data verified associations for 23 of the 26 loci implicated in previous studies and identified up 29 new loci with significant MS associations.


Journal: Nature Genetics. 2011 Jul 31. [Epub ahead of print]

Title: Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.

Authors: Hirota T, et al.

The researchers used the Illumina HumanHap 550v3 and 610-Quad BeadChips to genotype 1,532 Japanese individuals with adult asthma and 3,304 unaffected Japanese controls. By testing more than 100 suspicious variants in another 5,639 adult asthma patients and 24,608 controls, the team verified asthma associations for dozens of SNPs at five loci in the genome: two loci identified in past studies and three not detected before.

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Journal: Nature Genetics. 2011 Jul 31. [Epub ahead of print]

Title: Analysis of the coding genome of diffuse large B-cell lymphoma.

Authors: Pasqualucci L, et al.

The authors performed exome sequencing and microarray analyses on matched tumor-normal samples from six individuals to identify somatic mutations and copy number changes involved in samples from several sub-types of diffuse large B-cell lymphoma. After capturing non-repetitive protein-coding sequencing with the NimbleGen Sequence Capture Human Exome 2.1M array, the team sequenced the exomes with the Roche 454 GS FLX. The researchers also used Affymetrix SNP 6.0 arrays to profile copy number patterns in the matched tumor-normal samples before screening 73 more DLBCL tumor samples obtained from biopsies. They detected dozens of mutations per case, affecting many of the genes previously been linked to DLBCL.


Journal: Nature Genetics. 2011 Aug 14. [Epub ahead of print]

Title: A copy number variation morbidity map of developmental delay.

Authors: Cooper G, et al.

To explore the role of CNVs in developmental delay, the authors conducted analyses of 15,767 children with a wide range of intellectual disability or developmental delay conditions. Among the children tested, 73 percent had been classified as having an intellectual disability, developmental delay, and autism spectrum disorder, while the other cases had cognitive abnormalities or had conditions that weren't annotated. The cases were collected and tested at Signature Genomics using customized array comparative genomic hybridization with nine custom platforms, mostly an Agilent Technologies-manufactured array with 97,000 probes.


Journal: Nature Medicine. 2011 Jul 24;17(8):941-3.

Title: Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma.

Authors: Best T, et al.

The authors used the Affymetrix SNP 6.0 array to genotype 178 individuals who had been treated for Hodgkin's disease between the ages of eight and 20 years old, including 96 individuals who had developed a second malignant neoplasms-related cancer within six to 34 years of treatment and 82 who had not developed a second cancer over 27 to 38 years of follow up. In the process, the researchers found three SNPs — two on chromosome 6 and one on chromosome 18 — that they went on to test in another 62 Hodgkin's survivors who'd developed a second cancer and 71 who hadn't. The two chromosome 6 variants, both between the ATG5 and PRDM1 genes, were associated with SMN development in the replication group.


Journal: New Microbiology. 2011 Jul;34(3):307-16.

Title: The protein "mycoarray": a novel serological assay for the laboratory diagnosis of primitive endemic mycoses.

Authors: Ardizzoni A, et al.

A protein microarray containing fungal antigens, dubbed the "mycoarray," was developed to provide serodiagnosis of primitive endemic mycoses. The mycoarray consists of antigen extracts spotted on microarray slides. The arrays were processed with coccidioidomycosis and histoplasmosis patients' sera or with control sera and the occurring immunocomplexes were detected by indirect immunofluorescence. The results distinguished between histoplasmosis and coccidioidomycosis patients. In addition, the assay could discriminate between IgM and IgG antibody reactivity.


Journal: PLoS Pathogens. 2011 Jul;7(7):e1002155.

Title: Cross-species transmission of a novel adenovirus associated with a fulminant pneumonia outbreak in a new world monkey colony.

Authors: Chen E, et al.

Researchers at the University of California in San Francisco used array technology to identify an adenovirus that spread through a California monkey colony in 2009 and also infected a human researcher and two family members. Specifically, the UCSF researchers, used the center's ViroChip to study sera from the infected monkeys. The array, manufactured by Agilent Technologies, covers about 1,800 viruses. The UCSF team found that the new virus belonged to the adenovirus family, but was unlike any adenovirus ever reported to infect humans or monkeys. According to the paper, it shares only 56 percent of its DNA with its closest viral relative. Because the virus is so unusual, the authors suggested that it may have originated from a third, unidentified species.

BioArray News spoke with the authors of the paper last month (BAN 7/19/2011)


Journal: Prenatal Diagnostics. 2011 Aug;31(8):778-87.

Title: The development of a rapid assay for prenatal testing of common aneuploidies and microdeletion syndromes.

Authors: Shaffer L, et al.

The authors aimed to develop a prenatal assay for pregnancies with high likelihood of normal karyotypes, using BACs-on-Beads technology, a suspension array-based multiplex assay that relies on Luminex xMAP technology to detect gains and losses in chromosomal DNA. Fifteen relatively common microdeletions were selected that are not detectable, or may be missed, by karyotyping. Chromosomes 13, 18, 21, X, and Y were included. The authors validated the assay with 430 samples, and reported that all microdeletions and aneuploidies were correctly identified.


Journal: Reproductive Biomedicine Online. 2011 Aug;23(2):234-44.

Title: Methodology matters: IVF versus ICSI and embryonic gene expression.

Authors: Bridges P, et al.

The objective of this study was to determine differences in gene expression of blastocysts generated by intracytoplasmic sperm injection as well as ICSI with artificial oocyte activation versus in vitro fertilization, providing genetic information that can be used to aid in the diagnosis or treatment of those adversely affected by assisted reproduction treatment, as well as stimulate research to further refine these techniques. Murine blastocysts were generated by ICSI, ICSI-A and IVF, and processed for a microarray-based analysis of gene expression. Ten blastocysts were pooled for each procedure and three independent replicates generated. The data were then processed to determine differential gene expression and to identify biological pathways affected by the procedures.


Journal: Science. 2011 Aug 5;333(6043):724-9.

Title: Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.

Authors: Yuan J, et al.

This research team screened more than 2,800 compounds in 61 malaria parasite lines, identifying 32 compounds that were active against the majority of the parasite lines tested. They also identified genetic loci linked to differential chemical phenotypes — differences in how various Plasmodium falciparum strains react to various concentrations of a given compound — along with a trio of genes that influenced treatment response in most P. falciparum lines. A follow-on array-based association study of 3,354 SNPs combined with follow-up linkage analyses identified genetic loci associated with such drug response differences.

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