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In Print: Last Month's Microarray Papers of Note: Nov 1, 2011

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Microarray Papers of Note Published September and October 2011

Journal: ACS Nano. 2011 Oct. 25;5(10):8080-8.

Title: Nanopore-based single-molecule mass spectrometry on a lipid membrane microarray.

Authors: Baaken G, et al.

The authors describe a new, chip-based nanopore microarray. Lipid bilayers of less than 20 nanometers in diameter containing single alpha-hemolysin pores were formed on arrays of subpicoliter cavities containing individual microelectrodes, and ion conductance-based single-molecule mass spectrometry was performed on mixtures of poly(ethylene glycol) molecules of different length. The authors demonstrate the function of the device as a chip-based platform for array-format nanopore recordings with a resolution at least equal to that of established single microbilayer supports.


Journal: American Journal of Human Genetics. 2011 Oct. 7;89(4):516-28.

Title: Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania.

Authors: Reich D, et al.

The researchers genotyped 260 individuals from 33 populations including East Asian, Southeast Asian, New Guinean, Fijian, Polynesian, Australian, and Indian with the Affymetrix SNP 6.0 array to determine the presence and proportion of Denisovan DNA in individuals from Southeast Asia and Oceania. They also used the Illumina GAIIx to sequence the genomes of two individuals: a highlander from Papua New Guinea and an individual from the Mamanwa Negrito population in the Philippines. The results suggest that there were two migrations into the regions, with Denisovans interbreeding with the ancestors of the modern humans who ended up in parts of the Philippines, Australia, and New Guinea.


Journal: Analytical Biochemistry. 2011 Sept. 21. [Epub ahead of print]

Title: A secreted protein microarray platform for extracellular protein interaction discovery.

Authors: Ramani , et al.

To evaluate the performance of the functional protein microarray platform, the authors screened a set of 89 immunoglobulin (Ig)-type receptors against a highly diverse extracellular protein microarray with 686 genes represented. To enhance detection of low-affinity interactions, they developed a method to assemble bait Fc fusion proteins into multivalent complexes using protein A microbeads. Based on these screens, they developed a statistical methodology for hit calling and identification of nonspecific interactions on protein microarrays. The authors found that the Ig receptor interactions identified using the methodology resulted in a 70 percent true-positive to false-positive hit ratio.


Journal: Analytical and Bioanalytical Chemistry. 2011 Oct. 26. [Epub ahead of print]

Title: Direct immobilization of DNA probes on non-modified plastics by UV irradiation and integration in microfluidic devices for rapid bioassay.

Authors: Sun Y, et al.

The authors describe a method of using ultraviolet irradiation to directly immobilize poly(T)poly(C)-tagged DNA oligonucleotide probes on many different types of plastics without any surface modification. Using this microarray fabrication technique, a portable cyclic olefin copolymer biochip containing eight individually addressable microfluidic channels was developed and used for identification of avian influenza virus by DNA hybridization. The authors claim the DNA-linking method on non-modified polymers simplifies microarray fabrication procedures and permits flexibility in plastic material selection.


Journal: Astrobiology. 2011 Oct. 19. [Epub ahead of print]

Title: Immunological detection of small organic molecules in the presence of perchlorates: relevance to the Life Marker Chip and life detection on Mars.

Authors: Rix C, et al.

The planned 2018 ExoMars mission payload includes the Life Marker Chip instrument, capable of detecting biomarker molecules of extant and extinct Earth-like life in liquid extracts of Martian samples with an antibody microarray assay. In this paper, the authors investigated whether the presence of perchlorate salts, at levels similar to those at the NASA Phoenix landing site, would compromise the LMC extraction and detection method. They found no significant change in immunoassay function when using pyrene standards with added perchlorate salts and argue that the presence of perchlorate salts, at levels similar to those detected at the NASA Phoenix landing site, is unlikely to prevent the LMC from extracting and detecting organic molecules from Martian samples.

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Journal: BMC Cancer. 2011 Oct.11;11:437.

Title: A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence.

Authors: Reis P, et al.

The researchers used Affymetrix HG-U133A 2.0 plus oligonucleotide microarrays to assess gene expression patterns in 96 cancerous and non-cancerous oral tissues collected from 24 individuals who had been surgically treated for oral squamous cell carcinoma. To this data, the team added information from a meta-analysis that they did using publicly available raw gene expression data for 141 oral squamous cell carcinoma samples, 38 nearby normal tissues, and 20 unaffected tissues from five published datasets. In the process, they found 138 genes whose expression was at least twice as high in the oral cancer samples than in non-cancerous tissue samples. By comparing gene expression in tumor, margin, and normal oral tissues, they then narrowed in on four genes — MMP1, COL4A1, P4HA2, and THBS2 — whose over-expression in tissue at the margins of resected tumors corresponded to cancer recurrence.


Journal: Cell. 2011 Sept. 16;146(6):889-903.

Title: Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.

Authors: Liu P, et al.

The researchers did copy number and breakpoint analyses on samples from 10 males and seven females with complex genomic rearrangements and developmental delay or cognition problems. They performed comparative genomic hybridization and SNP analyses with several Agilent, NimbleGen, and Illumina arrays, as well as fluorescence in situ hybridization, to look at these rearrangements at increasingly refined resolutions. The authors determined that constitutional CGR shares features with chromothripsis observed in cancer cells, that CGR can involve replication-based mechanisms, and that chromosome catastrophe can occur throughout an organism's life cycle


Journal: European Journal of Human Genetics. 2011 Sept. 21 [Epub ahead of print]

Title: Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics.

Authors: Hanemaaijer N, et al.

The authors aimed to develop guidelines for interpreting gains detected by array analysis using array CGH data of 300 patients analyzed with the 105K Agilent Technologies oligo array in a diagnostic setting. Then they evaluated the guidelines in a second, independent, cohort of 300 patients. Most gains were concluded to be benign CNVs. Clinically relevant gains ranged from 288 to 7,912  kilobases in size, and were significantly larger than benign gains and gains of unknown clinical relevance. The authors concluded that a threshold of 200  kilobases is acceptable in a clinical setting, whereas heritability does not exclude a pathogenic nature of a gain.


Journal: European Journal of Human Genetics. 2011 Sept. 28 [Epub ahead of print]

Title: De novo deletions and duplications detected by array CGH: a study of parental origin in relation to mechanisms of formation and size of imbalance.

Authors: Sibbons S, et al.

The authors report on a series of 173 patients with physical and/or neurological abnormalities and a de novo imbalance identified by array CGH. Breakpoint intervals were screened for the presence of low copy repeats to distinguish between rearrangements formed by non-allelic homologous recombination and rearrangements formed by other mechanisms. The authors identified significant differences in size and parental origin between the LCR-mediated and non-LCR groups.


Journal: Genome Research. 2011 Oct. 21(10):1746-56.

Title: Genome-based analysis of the nonhuman primate Macaca fascicularis as a model for drug safety assessment.

Authors: Ebeling M, et al.

The researchers used Roche 454's Genome Sequencer FLX System to decode the genome of a Macaca fascicularis female of Mauritian origin with 6-fold coverage. Then they built a M. fascicularis-specific gene expression microarray on the Roche NimbleGen 12x135K platform to enable transcriptome analysis. The comparative expression analysis of liver samples from 36 animals of different geographic origin resulted in the identification of over 700 genes with highly variable expression while the majority of the transcriptome showed relatively stable expression with low inter-animal variation.


Journal: Gut. 2011 Oct. 60(10):1317-26.

Title: Integrative analysis of array-comparative genomic hybridization and matched gene expression profiling data reveals novel genes with prognostic significance in esophageal adenocarcinoma.

Authors: Goh X, et al.

Array-comparative genomic hybridization analysis was carried out on 56 fresh frozen esophageal adenocarcinoma resection samples with long-term clinical follow-up data. Samples with aberrations were further analyzed with whole-genome SNP arrays to confirm aCGH findings. Matched gene expression microarray data were used to identify genes with high copy number-expression correlations. Nested-multiplex PCR on DNA from microdissected specimens and fluorescence in situ hybridization assays were used for target validation. Immunohistochemistry on the same cohort and 371 independent samples was used for subsequent validation. CGH identified 17 common regions of gains and 11 common regions of losses. Integration of CGH data with matched gene expression microarray data highlighted genes with high copy number-expression correlations: two deletions (p16/CDKN2A, MBNL1) and four gains (EGFR, WT1, NEIL2, MTMR9). Immunohistochemistry demonstrated protein over-expression of targets with gains: EGFR, WT1, NEIL2, and MTMR9.


Journal: Human Molecular Genetics. 2011 Oct. 1;20(19):3769-78.

Title: Diverse mutational mechanisms cause pathogenic subtelomeric rearrangements.

Authors: Luo Y, et al.
The authors coupled high-resolution array CGH with breakpoint junction sequencing of a diverse collection of subtelomeric rearrangements. They analyzed 102 breakpoints corresponding to 78 rearrangements involving 28 chromosome ends. Sequencing 21 breakpoint junctions revealed signatures of non-homologous end-joining, non-allelic homologous recombination between interspersed repeats and DNA replication processes. They concluded that subtelomeric rearrangements arise from diverse mutational mechanisms. They also found hotspots of subtelomeric breakage at the end of chromosomes 9q and 22q and argue that the sites may correspond to genomic regions that are particularly susceptible to double-strand breaks.


Journal: Investigative Opthamology & Visual Science. 2011 Oct 24. [Epub ahead of print]

Title: High-throughput Retina-Array for screening 93 genes involved in inherited retinal dystrophy.

Authors: Song J, et al.

A custom 300 kilobase Affymetrix resequencing chip, the Retina-Array, was developed to detect sequence alterations of 267,550 bases of both sense and antisense sequence in 1,470 exons spanning 93 genes involved in inherited retinal dystrophy. Retina-Array was evaluated in 19 patient samples with inherited RD and four reference samples. In total, 304 candidate variations were identified using a series of customized screening filters.


Journal: Nanoscale Research Letters. 2011 Oct. 4;6:540.
Title: Superparamagnetic iron oxide nanoparticle attachment on array of micro test tubes and microbeakers formed on p-type silicon substrate for biosensor applications.
Authors: Goshal S, et al.
A uniformly distributed array of micro test tubes and microbeakers was formed on a p-type silicon substrate with tunable cross-section and distance of separation by anodic etching of the silicon wafer in N-dimethylformamide and hydrofluoric acid, which led to the formation of macroporous silicon templates. The authors also synthesized superparamagnetic iron oxide nanoparticles, with average particle size approximately 20 nanometers, and attached them on the porous silicon chip surface as well as on the pore walls.


Journal: Nature. 2011 Oct. 26;478(7370):519-23.

Title: Temporal dynamics and genetic control of transcription in the human prefrontal cortex.

Authors: Colantuoni C, et al.

Researchers from the National Institutes of Health, Illuminato Biotechnology, and Johns Hopkins University used microarrays to obtain gene expression and genotype information on 269 post-mortem brain samples. With this data in hand, they then looked at the nature, timing, and control of gene expression in the prefrontal cortex across development and aging, from as early as two weeks after conception to the age of 80 years old.


Journal: Nature Genetics. 2011 Oct 16;43(11):1131-8.

Title: Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Authors: Chambers J, et al.

The authors carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations. They used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions, and identified 69 candidate genes, including genes involved in biliary transport, glucose, carbohydrate and lipid metabolism, glycoprotein biosynthesis and cell surface glycobiology, inflammation and immunity, and glutathione metabolism.


Journal: Nature Genetics. 2011 Oct. 23. [Epub ahead of print]

Title: Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.

Authors: Zhang F, et al.

Using Illumina arrays, the authors performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy, according to the authors.


Journal: Prenatal Diagnosis. 2011 Oct. 24. [Epub ahead of print]

Title: Prenatal genetic diagnosis using microarray analysis in fetuses with congenital heart defects.

Authors: Schmid M, et al.

Twelve consecutive fetuses with congenital heart defects but normal karyotype and normal fluorescence in situ hybridization results for the DiGeorge region were examined for chromosomal aberrations by genomic microarray analysis. At 1- megabase resolution, potentially causal copy number variations were identified in three out of 12 fetuses. At higher resolution, aberrations with uncertain significance were identified in a further three cases.


Journal: Science. 2011 Oct. 7. [Epub ahead of print]

Title: A map of local adaptation in Arabidopsis thaliana.

Authors: Fournier-Level A, et al.

The authors genotyped plants grown in field sites in Halle in Germany, Norwich in the UK, Oulu in Finland, and Valencia in Spain at more than 213,000 SNPs in the genome, looking for variants that affect survival and reproductive fitness at each of the sites. They also analyzed SNPs coinciding with survival and fitness at each location to see how they related to 11 climate-related variables. They reported that the loci linked to survival and fitness varied depending on the site at which plants were sampled.


Journal: Ultrasound in Obstetrics and Gynecology. 2011 Sept. 38(3):314-9.

Title: Identification of submicroscopic chromosomal aberrations in fetuses with increased nuchal translucency and apparently normal karyotype.

Authors: Leung T, et al.

The aim of this study was to report the prevalence of submicroscopic chromosomal abnormalities in a cohort of apparently euploid fetuses that presented with increased nuchal translucency. The samples were examined by microarray-based comparative genomic hybridization using a 44K oligonucleotide array specifically constructed for prenatal screening. CNVs were reported in six out of 48 cases, or 12.5 percent, by aCGH and the microdeletions or microduplications ranged from 1.1 to 7.9 megabases. Following validation, four cases, or 8.3 percent, were considered to be pathogenic and clinically significant.

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