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In Print: Jul 12, 2011

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Microarray Papers of Note Published June 2011

Journal: Analytical Chemistry. 2011 Jun 28. [Epub ahead of print]

Title: Etched glass microarrays with differential resonance for enhanced contrast and sensitivity of SPR imaging analysis.

Authors: Linman M, et al.

The authors report the fabrication and characterization of gold-coated etched glass array substrates for surface plasmon resonance imaging analysis with enhanced performance in image contrast and sensitivity. The etching of the glass substrate induces a variation in the resonance condition and in the resonance angle between the etched wells and the surrounding area, leading to the isolation of the array spot resonance with a reduction of the background signal. The reusability and enhanced performance of the etched glass array chips should find a broad range of applications, the authors argue.


Journal: Analytical Chemistry. 2011 Jun 23. [Epub ahead of print]

Title: Taguchi design-based optimization of sandwich immunoassay microarrays for detecting breast cancer biomarkers.

Authors: Luo W, et al.

Taguchi design, a statistics-based design for experimental methods, is used for optimization of products and complex production processes in many different industries. In this paper, the authors used the method to optimize an antibody sandwich immunoassay microarray with five breast cancer biomarkers: CA15-3, CEA, HER2, MMP9, and uPA. Two successive optimization rounds with 16 experimental trials were performed. After Taguchi optimization, the assay sensitivity was improved between seven and 68 times, depending on the analyte, and the maximal signal intensity increased between 1.8 and 3 times.


Journal: Analytical Chemistry. 2011 Jun 1;83(11):4118-25.

Title: Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis.

Authors: Kwon C, et al.

The authors designed a microarray platform for cell-based screening. The device creates a microarray of 2,100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells, creating a microarray of sealed microscale cell cultures each with unique conditions. In the paper, the authors describe how they used the device to screen the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds.


Journal: Atherosclerosis. 2011 Jun;216(2):383-9.

Title: Array-based resequencing for mutations causing familial hypercholesterolemia.

Authors: Chiou K, et al.

The authors developed an array-based resequencing assay to facilitate genetic testing in familial hypercholesterolemia patients. The custom DNA resequencing array can detect mutations on all 3 FH-causing genes — LDL receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 gene, as well as 290 known insertion/deletion mutations on LDLR. The authors verified the FH array's performance by analyzing 35 previously sequenced subjects and blindly screening 125 FH patients. The average microarray call rate was 98.45 percent and the agreement between microarray and capillary sequencing was 99.99 percent.


Journal: Biomedical Microdevices. 2011 Jun;13(3):533-8.

Title: Development and characterization of a disposable plastic microarray printhead.

Authors: Griessner M, et al.

The authors describe 8-channel plastic microarray printheads. The use of plastics minimizes the need for surface modifications required previously for proper printing results, they argue, while regeneration processes, cleaning procedures, and contaminations caused by residual samples can be avoided. Plastic printheads can also be used to print viscous liquids, such as cell suspensions or whole blood. Additionally, functional parts within the plastic printhead, such as particle filters, can be included.

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Journal: BMC Cancer. 2011 Jun 16;11:253.

Title: Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens.

Authors: Sadi A, et al.

A modified RNA extraction method and a recently developed DNA microarray technique called cDNA-mediated annealing, selection, extension, and ligation were evaluated. The gene profiles generated from formalin-fixed, paraffin-embedded breast cancer specimens were compared to those obtained from paired fresh fine needle aspiration biopsies of 25 breast cancers of different clinical subtypes based on ER and Her2/neu status. Selected RNA levels were validated using RT-qPCR, and two public databases were used to demonstrate the prognostic significance of the gene profiles generated from FFPE specimens.


Journal: BMC Genomics. 2011 Jun 23;12(1):326. [Epub ahead of print]

Title: Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis.

Authors: Llorens F, et al.

This team of researchers from the University of Barcelona combined three different microarray platforms — from Agilent, Operon, and Illumina — with digital gene-expression profiling on the Illumina Genome Analyzer to study genes related to the epidermal growth factor, a regulatory growth factor related to cell proliferation and survival. They found that the combination of the techniques was able to establish a validated gene set — including novel genes previously unrelated to EGF — as well as help piece together the network of how those genes interact.


Journal: BMC Microbiology. 2011 Jun 14;11:132.

Title: A species independent universal bio-detection microarray for pathogen forensics and phylogenetic classification of unknown microorganisms.

Authors: Shallom S, et al.

A sequence-independent chip, called the Universal Bio-Signature Detection Array, was designed with approximately 373,000 probes. Each genome hybridized on the array has a unique pattern of signal intensities corresponding to each of these probes. Signal intensities were used to generate an unbiased cluster analysis of signal intensity hybridization patterns that can distinguish species into accepted and known phylogenomic relationships. The array is also able to detect synthetically mixed pathogens.


Journal: Genetics in Medicine. 2011 Jun 28. [Epub ahead of print]

Title: Chromosomal microarray testing influences medical management.

Authors: Coulter M, et al.

The authors conducted a retrospective chart review of chromosomal microarray testing performed during a 12-month period on patients with developmental disorder, autism spectrum disorder, and congenital anomalies to determine the proportion of cases where abnormal CMA results impacted recommendations for clinical action. They found that, for all test indications, CMA results influenced medical management in a majority of patients with abnormal variants. The results, they argue, support the use of CMA as a clinical diagnostic test that influences medical management.


Journal: Human Molecular Genetics. 2011 Jun 4. [Epub ahead of print]

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

Authors: Nakabayashi K, et al.

Relying on rare reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotypes, the authors analyzed CpG dinucleotides present in the human genome for imprinted differentially methylated regions using the Illumina Infinium methylation27 BeadChip microarray. This 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: a maternally methylated region overlapping the FAM50B promoter CpG island, and a paternally methylated, bidirectional repressor located between maternally expressed ZNF597 and NAT15 genes. These three genes are biallelically expressed in mice due to lack of differential methylation, suggesting that these genes have become imprinted after the divergence of mouse and humans, the authors note.

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Journal: Human Reproduction. 2011 Jun;26(6):1560-74.

Title: First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis.

Authors: Alfarawati S, et al.

The authors explored the use of conventional metaphase comparative genomic hybridization and microarray as alternatives for preimplantation genetic diagnosis of chromosome rearrangements. The study included 16 patients who underwent 20 cycles of PGD for a variety of chromosome rearrangements. Of the 15 patients who completed their treatment cycles, five became pregnant after one or two cycles, resulting in four healthy births. The delivery rate per cycle was 21 percent or 27 percent per embryo transfer. The authors argue that by using these methods, most patients requesting PGD for a chromosome rearrangement can be treated using a single protocol. The detection of abnormalities affecting chromosomes unrelated to the rearrangement may assist in the selection of viable embryos for transfer, they state.


Journal: Journal of Biological Chemistry. 2011 Jun 17;286(24):21623-32.

Title: Single cell time-resolved quorum responses reveal dependence on cell density and configuration.

Authors: Whitaker R, et al.

This study presents a method for analyzing bacterial communication by investigating single-cell responses. The authors applied a fiber-optic microarray to record cellular communication from single cells. They employed this method to detect how genes under quorum regulation are induced or repressed over time on the single-cell level and to determine whether cellular density and configuration are indicative of the single-cell temporal patterns of gene expression.


Journal: Journal of Experimental Medicine. 2011 June 13 [Epub ahead of print]

Title: Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation.

Authors: Fabbri G, et al.

The authors of this study used the Roche NimbleGen 2.1M human exome array to capture protein-coding regions for five chronic lymphocytic leukemia tumors and matched normal genomes from individuals who had been diagnosed with the disease but had not yet received any treatment. They then sequenced these regions with the Roche 454 GS FLX. They also used the Affymetrix SNP 6.0 Array for copy number analysis. While the exomes contained relatively modest numbers of mutations overall, the team found an over-representation of mutations in the transmembrane protein coding gene NOTCH1. Their subsequent screens of CLL tumors, corresponding normal samples, and clinical samples indicate that activating mutations in NOTCH1 tend to coincide with particularly aggressive forms of CLL and poor survival rates.


Journal: Molecular Biosystems. 2011 Jun;7(6):1902-7.

Title: A PNA microarray for tomato genotyping.

Authors: Tedeschi T, et al.

The authors describe a peptide nucleic acid microarray for the identification of SNPs characteristic of seven different tomato varieties. Highly selective arginine-based, monomer-containing PNAs were used in order to obtain very selective probes. PNA microarrays based on these probes were prepared and applied to SNP discrimination in model experiments using oligonucleotide mixtures simulating the different sequences of the seven tomato varieties.


Journal: Nature Biotechnology. 2011 June 11;29(6):512-20.

Title: Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants.

Authors: Pinto D, et al.

The researchers tested 11 different microarray platforms and found that current methods of analysis only detect a portion of the CNVs in the genome in any given experiment. According to the paper, for most microarray platforms, reproducibility of replicate samples is below 70 percent and results from different analysis tools applied to the same data typically show less than 50 percent reproducibility. These and other findings led the researchers to conclude that using multiple microarray platforms and a combination of algorithms will lead to a better discovery yield of CNVs.

BioArray News spoke with the study authors about their findings last month (BAN 6/21/2011).


Journal: Nucleic Acids Research. 2011 Jun 30. [Epub ahead of print]

Title: Specific sequence determinants of miR-15/107 microRNA gene group targets.

Authors: Nelson P, et al.

Using anti-Argonaute antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, RNA immunoprecipitation-on-chip experiments were performed in cultured H4 cells after transfection with microRNAs corresponding to the miR-15/107 gene group, and five control miRNAs. Three biological replicates were run for each condition with a total of 54 separate human Affymetrix Human Gene 1.0 ST array replicates. Computational analyses queried for determinants of miRNA:mRNA binding. According to the authors, RIP-chip studies correlated with total input mRNA profiling provides more comprehensive information than using either RIP-chip or total mRNA profiling alone after miRNA transfections.


Journal: Prenatal Diagnostics. 2011 Jun 21 [Epub ahead of print]

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

Authors: Shaffer L, et al.

The authors developed a prenatal assay for pregnancies with high likelihood of normal karyotypes, using BACs-on-Beads technology, a suspension array-based multiplex assay that employs Luminex xMAP technology, for the detection of gains and losses in chromosomal DNA. Fifteen relatively common microdeletions were selected that are not detectable, or may be missed, by karyotyping and usually do not present with abnormal ultrasound findings. Chromosomes 13, 18, 21, X, and Y were included. The authors validated the assay with 430 samples.


Journal: Proceedings of the National Academy of Sciences. 2011 Jun 14;108(24):9747-52.

Title: Elucidating glycosaminoglycan-protein-protein interactions using carbohydrate microarray and computational approaches.

Authors: Rogers C, et al.

The authors used carbohydrate microarrays and computational modeling methodologies to elucidate glycosaminoglycan-protein interactions. The approach was validated through the study of known protein partners for heparan and chondroitin sulfate, including fibroblast growth factor 2 and its receptor FGFR1, the malarial protein VAR2CSA, and tumor necrosis factor-α. They argue that their combined microarray and computational modeling methodologies provide a means to identify new glycosaminoglycan-protein-protein interactions, as well as a molecular-level understanding of those complexes.


Journal: Veterinary Microbiology. 2011 Jun 2;150(3-4):309-14.

Title: Microarray-based genotyping of Staphylococcus aureus isolates from camels.

Authors: Monecke S, et al.

S. aureus is a common cause of mastitis and other diseases in camels. In order to obtain data on population structure as well as on the carriage of toxin genes and resistance markers, a collection of 45 isolates from dromedaries of Dubai, United Arab Emirates, were genotyped using microarrays. This study provides the first genotyping data on the population structure and the presence of toxin genes and resistance markers of S. aureus strains in Middle Eastern camels.

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Nature Papers Present Approach to Find Natural Products, Method to ID Cancer Driver Mutations, More

In Nature this week: combination of cryogenic electron microscopy with genome mining helps uncover natural products, driver mutations in cancer, and more.