CiteULike: Tag arrays

Unravelling Microbial Communities with DNA-Microarrays: Challenges and Future Directions

Wagner — 2007-07-02T21:31:41-00:00

Microbial Ecology, Vol. 53, No. 3. (April 2007), pp. 498-506.

Development of a statistically robust quantification method for microorganisms in mixtures using oligonucleotide microarrays

Alex Pozhitkov — 2008-05-09T15:08:22-00:00

Journal of Microbiological Methods, Vol. 70, No. 2. (August 2007), pp. 292-300.

High-density oligonucleotide arrays can be extremely useful for identifying and quantifying specific targets (i.e., ribosomal RNA of microorganisms) in mixtures. However, current array identification schemes are severely compromised by nonspecific hybridization, resulting in numerous false-positive and false-negative calls, they lack an adequate internal control for assessing the quality of identification, and are dependent on amplification of specific target sequences which introduce biases. We have developed a novel approach for the routine quantification and identification of metabolically active microorganisms in mixed samples. The advantage of our approach over conventional ones is that it avoids designing, optimizing, validating, and selecting oligonucleotide probes for arrays; also, nonspecific hybridization is no longer a problem. The basic principle of the approach is that a fluorescence pattern of a mixed sample is a superposition of the fluorescent patterns for each target. The superposition can be quantitatively deconvoluted in terms of concentrations of each microbe. We demonstrated the utility of our approach by extracting rRNA from three microorganisms, making test mixtures, labeling the rRNA, and hybridizing each test mixture to DNA oligonucleotide (20-mers, n = 346,608) arrays. Comparison of known concentrations of individual targets in mixtures to those estimated by the solution revealed highly consistent results. The goodness-of-fit of the solution revealed that about 90% of the variability in the data could be explained. A new analytical approach for microbial identification and quantification has been presented in this report. Our findings demonstrate that including signal intensity values from all duplexes on the array, which are essentially nonspecific to the target organisms, significantly improved predictions of known microbial targets. To our knowledge, this is the first study to report this phenomenon. In addition, we demonstrate that the method is a self-sufficient analytical procedure since it provides statistical confidence of the quantification.

Optimization of minuscule samples for use with cDNA microarrays.

Susan McLean Hunter — 2008-03-05T06:57:57-00:00

J Biochem Biophys Methods (23 December 2007)

The recent advent of microarray technology and RNA amplification allows us to compare the expression profiles of thousands of genes from small amounts of tissue or cells. We have compared and contrasted various methods of RNA preparation, RNA amplification, target labelling and array analysis in order to achieve a streamlined protocol for microarraying small samples. We have concluded that usage of the NIA 15K cDNA array set, in combination with RNA extraction using the Mini RNA Isolation kit (Zymo), amplification with the RiboAmp kit (Arcturus), followed by indirect labelling via the Atlastrade mark PowerScripttrade mark Fluorescent Labelling kit (using a modified protocol), is optimal with a material derived from either very early stage mouse embryos or individually picked embryonic stem cell colonies. Normalisation using the analysis package Limma (Bioconductor) with data normalisation by print tip Loess, using the "normexp" function with an offset of 50 for background adjustment, and incorporating A-quantile between array normalisation was best with our results. Furthermore, RT-PCR confirmation of array results is achievable without amplification, thereby controlling for amplification bias. These methods will be of great utility in mapping the transcriptome of embryonic and other small samples.

Power Sum Identities for Arbitrary Symmetric Arrays

HW Gould — 2006-09-27T06:18:28-00:00

SIAM Journal on Applied Mathematics, Vol. 17, No. 2. (1969), pp. 307-316.

A comprehensive SAGE database for the analysis of T cells

Jill Graff — 2006-03-24T11:35:53-00:00

International Immunology, Vol. 18, No. 4. (April 2006), pp. 613-626.

A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies

Winston Kuo — 2006-07-14T10:57:39-00:00

Nature Biotechnology, Vol. 24, No. 7. (02 July 2006), pp. 832-840.

Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies

Ke Hao — 2008-06-30T00:41:47-00:00

PLoS Genet, Vol. 4, No. 6. (27 June 2008), e1000109.

To facilitate whole-genome association studies (WGAS), several high-density SNP genotyping arrays have been developed. Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays. Ideally, such evaluations would be done on a SNP set and a cohort of individuals that are both independently sampled from the original SNPs and individuals used in developing the arrays. Without utilization of an independent test set, previous estimates of genetic coverage and statistical power may be subject to an overfitting bias. Additionally, the SNP arrays' statistical power in WGAS has not been systematically assessed on real traits. One robust setting for doing so is to evaluate statistical power on thousands of traits measured from a single set of individuals. In this study, 359 newly sampled Americans of European descent were genotyped using both Affymetrix 500K (Affx500K) and Illumina 650Y (Ilmn650K) SNP arrays. From these data, we were able to obtain estimates of genetic coverage, which are robust to overfitting, by constructing an independent test set from among these genotypes and individuals. Furthermore, we collected liver tissue RNA from the participants and profiled these samples on a comprehensive gene expression microarray. The RNA levels were used as a large-scale set of quantitative traits to calibrate the relative statistical power of the commercial arrays. Our genetic coverage estimates are lower than previous reports, providing evidence that previous estimates may be inflated due to overfitting. The Ilmn650K platform showed reasonable power (50% or greater) to detect SNPs associated with quantitative traits when the signal-to-noise ratio (SNR) is greater than or equal to 0.5 and the causal SNP's minor allele frequency (MAF) is greater than or equal to 20% (N = 359). In testing each of the more than 40,000 gene expression traits for association to each of the SNPs on the Ilmn650K and Affx500K arrays, we found that the Ilmn650K yielded 15% times more discoveries than the Affx500K at the same false discovery rate (FDR) level.

RNA-seq: An assessment of technical reproducibility and comparison with gene expression arrays

John Marioni — 2008-06-11T20:56:53-00:00

Genome Res. (11 June 2008), gr.079558.108.

Ultra high-throughput sequencing is emerging as an attractive alternative to microarrays for genotyping, analysis of methylation patterns and identification of transcription factor binding sites. Here, we describe an application of the Illumina sequencing platform to study mRNA expression levels. Our goals were to estimate technical variance associated with Illumina sequencing in this context and to compare its ability to identify differentially expressed genes with existing array technologies. To do so, we estimated gene expression differences between liver and kidney RNA samples using multiple sequencing replicates, and compared the sequencing data to results obtained from Affymetrix arrays using the same RNA samples. We find that the Illumina sequencing data are highly replicable, with relatively little technical variation, and so, for many purposes, it may suffice to sequence each mRNA sample only once (i.e., using one lane). The information in a single lane of Illumina sequencing data appears comparable to that in a single array in enabling identification of differentially expressed genes, while allowing for additional analyses such as detection of low-expressed genes, alternative splice variants, and novel transcripts. Based on our observations, we propose an empirical protocol and a statistical framework for the analysis of gene expression using ultra high-throughput sequencing technology. 10.1101/gr.079558.108

A hardware version of the RSA using the Montgomery's algorithm with systolic arrays

Ali Alkar — 2006-11-12T17:03:50-00:00

Integr. VLSI J., Vol. 38, No. 2. (December 2004), pp. 299-307.

Cold atoms in videotape micro-traps

Sinclair — 2008-02-12T22:29:00-00:00

The European Physical Journal D - Atomic, Molecular, Optical and Plasma Physics, Vol. 35, No. 1. (2005), pp. 105-110.

We describe an array of microscopic atom traps formed by a pattern of magnetisation on a piece of videotape. We describe the way in which cold atoms are loaded into one of these micro-traps and how the trapped atom cloud is used to explore the properties of the trap. Evaporative cooling in the micro-trap down to a temperature of K allows us to probe the smoothness of the trapping potential and reveals some inhomogeneity produced by the magnetic film. We discuss future prospects for atom chips based on microscopic permanent-magnet structures.

A scalable quantum computer with ions in an array of microtraps

JI Cirac — 2007-12-13T14:49:47-00:00

Nature, Vol. 404, No. 6778. (6 April 2000), pp. 579-581.

Micro-optical Realization of Arrays of Selectively Addressable Dipole Traps: A Scalable Configuration for Quantum Computation with Atomic Qubits

R Dumke — 2008-02-13T15:47:16-00:00

Physical Review Letters, Vol. 89, No. 9. (2002), 097903.

We experimentally demonstrate novel structures for the realization of registers of atomic qubits: We trap neutral atoms in one- and two-dimensional arrays of far-detuned dipole traps obtained by focusing a red-detuned laser beam with a microfabricated array of microlenses. We are able to selectively address individual trap sites due to their large lateral separation of 125 μm. We initialize and read out different internal states for the individual sites. We also create two interleaved sets of trap arrays with adjustable separation; as required for many proposed implementations of quantum gate operations.

Holographic generation of microtrap arrays for single atoms by use of a programmable phase modulator

Silvia Bergamini — 2008-02-14T21:44:31-00:00

J. Opt. Soc. Am. B, Vol. 21, No. 11. (1 November 2004), pp. 1889-1894.

We have generated multiple micrometer-sized optical dipole traps for neutral atoms using holographic techniques with a programmable liquid-crystal spatial light modulator. The setup allows storing of a single atom per trap and addressing and manipulation of individual trapping sites.

An Approach to Fast Arrays in Haskell

Manuel Chakravarty — 2007-11-06T22:36:26-00:00

Advanced Functional Programming (2003), pp. 27-58.

Many array-centric algorithms from computational science and engineering, especially those based on dynamic and irregular data structures, can be coded rather elegantly in a purely functional style. The challenge, when compared to imperative array languages, is performance. These lecture notes discuss the shortcomings of Haskell’s standard arrays in this context and present an alternative approach that decouples array from list processing and is based on program transformation and generic programming. In particular, we will present (1) an array library that uses type analysis to achieve unboxing and flattening of data structures as well as (2) equational array fusion based on array combinators and compiler-driven rewrite rules. We will make use of a range of advanced language extensions to Haskell, such as multi-parameter type classes, functional dependencies, rewrite rules, unboxed values, and locally state-based computations.

A Short Cut to Deforestation

Andrew Gill — 2007-11-15T15:25:21-00:00

(1993), pp. 223-232.

Lists are often used as "glue" to connect separate parts of a program together. We propose an automatic technique for improving the efficiency of such programs, by removing many of these intermediate lists, based on a single, simple, local transformation. We have implemented the method in the Glasgow Haskell compiler.

Constructing suffix arrays in linear time

Dong Kim — 2005-10-30T15:24:02-00:00

Journal of Discrete Algorithms, Vol. 3, No. 2-4. (June 2005), pp. 126-142.

The time complexity of suffix tree construction has been shown to be equivalent to that of sorting: O(n) for a constant-size alphabet or an integer alphabet and O(nlogn) for a general alphabet. However, previous algorithms for constructing suffix arrays have the time complexity of O(nlogn) even for a constant-size alphabet.In this paper we present a linear-time algorithm to construct suffix arrays for integer alphabets, which do not use suffix trees as intermediate data structures during its construction. Since the case of a constant-size alphabet can be subsumed in that of an integer alphabet, our result implies that the time complexity of directly constructing suffix arrays matches that of constructing suffix trees.

Mapping cellular transcriptosomes in autopsied Alzheimer's disease subjects and relevant animal models

Hemachandra Reddy — 2007-12-11T10:31:19-00:00

Neurobiology of Aging, Vol. 27, No. 8. (August 2006), pp. 1060-1077.

Alzheimer's disease (AD) is a late-onset and progressive neurodegenerative disorder characterized clinically by memory loss, impairment of other cognitive functions, and changes in behavior and personality. The overall aim of this review is to summarize recent advances in studies of AD progression and the use of animal models in gene expression studies of AD progression. Genetic causes of AD are known only for early-onset AD patients. For a majority of late-onset AD patients, causal factors are still unknown. Currently, there are no early detectable biomarkers for late-onset AD, and there is a lack of understanding of AD pathophysiology, particularly at the early stages of disease progression, before pathology develops. Human histopathological and biochemical studies provide valuable information regarding the last stages of AD pathogenesis. However, to understand early cellular changes in AD progression before symptoms develop, animal models are still our only alternative. Several research groups have created genetically engineered animal models, particularly models of the mouse, rat, fly, and worm, which have allowed us to better, understand the initiating events of AD progression. Recently, state-of-the-art methods have helped elucidate gene expression changes in affected and unaffected tissues from postmortem AD brains and from animal models developed for AD studies. These methods allow the investigation of mRNA-based transcriptosomal profiles of brain specimens from AD humans and transgenic animals. The major finding from these studies is that AD progression and pathogenesis involve multiple cellular pathways, which suggests that AD is a complex and heterogeneous disease.

Glass Surfaces Grafted with High-Density Poly(ethylene glycol) as Substrates for DNA Oligonucleotide Microarrays

R Schlapak — 2007-08-13T20:39:11-00:00

Langmuir, Vol. 22, No. 1. (3 January 2006), pp. 277-285.

Abstract: Surfaces carrying a dense layer of poly(ethylene glycol) (PEG) were prepared, characterized, and tested as substrates for DNA oligonucleotide microarrays. PEG bis(amine) with a molecular weight of 2000 was grafted onto silanized glass slides bearing aldehyde groups. After grafting, the terminal amino groups of the PEG layer were derivatized with the heterobifunctional cross-linker succinimidyl 4-[p-maleimidophenyl]butyrate to permit the immobilization of thiol-modified DNA oligonucleotides. The stepwise chemical modification was validated with X-ray photoelectron spectroscopy. Goniometry indicated that the PEG grafting procedure reduced surface inhomogeneities present after the silanization step, while atomic force microscopy and ellipsometry confirmed that the PEG layer was dense and monomolecular. Hybridization assays using DNA oligonucleotides and fluorescence imaging showed that PEG grafting improved the yield in hybridization 4-fold compared to non-PEGylated maleimide-derivatized surfaces. In addition, the PEG layer reduced the nonspecific adsorption of DNA by a factor of up to 13, demonstrating that surfaces with a dense PEG layer represent suitable substrates for DNA oligonucleotide microarrays.

Methods for fabricating arrays of holes using interference lithography

A Fernandez — 2007-09-04T23:07:10-00:00

Journal of Vacuum Science \amp Technology B: Microelectronics and Nanometer Structures, Volume 15, Issue 6, November 1997, pp.2439-2443, Vol. 15 (November 1997), pp. 2439-2443.

Not Available

Use of interference lithography to pattern arrays of submicron resist structures for field emission flat panel displays

A Fernandez — 2007-09-04T23:05:22-00:00

Journal of Vacuum Science \amp Technology B: Microelectronics and Nanometer Structures, Volume 15, Issue 3, May 1997, pp.729-735, Vol. 15 (May 1997), pp. 729-735.

Not Available

Interferometric lithography of sub-micrometer sparse hole arrays for field-emission display applications

X Chen — 2007-09-04T23:02:04-00:00

Journal of Vacuum Science \amp Technology B: Microelectronics and Nanometer Structures, Volume 14, Issue 5, September 1996, pp.3339-3349, Vol. 14 (September 1996), pp. 3339-3349.

Not Available

Rapid communication Fabrication of nano-dot- and nano-ring-arrays by nanosphere lithography

M Winzer — 2007-08-02T21:17:34-00:00

Applied Physics A: Materials Science & Processing, Vol. 63 (1996), pp. 617-619.

We have applied the method of nanosphere lithography to fabricate arrays of nanometer-scale gold and cobalt particles. The individual cobalt particles were found to be in a single domain state as verified by magnetic force microscopy. By tuning the preparation conditions, we also successfully fabricated arrays of mesoscopic gold rings for the first time with potential application for persistent current experiments.

Nanoparticle optics: The importance of radiative dipole coupling in two-dimensional nanoparticle arrays

CL Haynes — 2007-03-08T23:38:59-00:00

J Phys Chem B, Vol. 107, No. 30. (2003), pp. 7337-7342.

In this paper, the electromagnetic interactions between noble metal nanoparticles are studied by measuring the extinction spectra of two-dimensional arrays of Au and Ag cylinders and trigonal prisms that have been fabricated with electron beam lithography. The nanoparticles are typically 200 nm in diameter and 35 nm in height; both hexagonal and square array patterns have been considered with lattice spacings that vary from 230 to 500 nm. The extinction spectra typically have a maximum in the 700-800 nm region of the spectrum, and this maximum blue shifts as lattice spacing is reduced, having typically a 40 nm decrease in ?max for a 100 nm decrease in lattice spacing. The results are similar for the different noble metals, array patterns, and nanoparticle shapes. The extinction spectra have been modeled using coupled dipole calculations, and the observed spectral variations are in good qualitative agreement with experimental data. Moreover, the computational analysis indicates that the blue shifts are due to radiative dipolar coupling between the nanoparticles and retardation effects. These effects result in a net depolarization of the dipole couplings for lattice spacings of 200-500 nm.

Detecting genetic variation in microarray expression data

Jennifer Greenhall — 2007-07-05T19:56:30-00:00

Genome Res. (3 July 2007), gr.6307307.

The use of high-density oligonucleotide arrays to measure the expression levels of thousands of genes in parallel has become commonplace. To take further advantage of the growing body of data, we developed a method, termed "GeSNP," to mine the detailed hybridization patterns in oligonucleotide array expression data for evidence of genetic variation. To demonstrate the performance of the algorithm, the hybridization patterns in data obtained previously from SAMP8/Ta, SAMP10/Ta, and SAMR1/Ta inbred mice and from humans and chimpanzees were analyzed. Genes with consistent strain-specific and species-specific hybridization pattern differences were identified, and [~]90% of the candidate genes were independently confirmed to harbor sequence differences. Importantly, the quality of gene expression data was also improved by masking the probes of regions with putative sequence differences between species and strains. To illustrate the application to human disease groups, data from an inflammatory bowel disease study were analyzed. GeSNP identified sequence differences in candidate genes previously discovered in independent association and linkage studies and uncovered many promising new candidates. This approach enables the opportunistic extraction of genetic variation information from new or pre-existing gene expression data obtained with high-density oligonucleotide arrays. 10.1101/gr.6307307

Subpixel motion computing architecture

J Diaz — 2008-02-20T06:59:28-00:00

IEE Proceedings Vision, Image and Signal Processing, Vol. 153, No. 6. (December 2006), pp. 869-880.

A pipelined optical-flow processing system that works as a virtual motion sensor has been described. It is based on a field programmable gate array (FPGA) device enabling the easy change of configuring parameters to adapt the sensor to different speeds, light conditions and other environmental factors. It is referred to as a `virtual sensor' because it consists of a conventional camera as front-end supported by an FPGA processing device, which embeds the frame grabber, optical-flow algorithm implementation, output module and some configuration and storage circuitry. This is the first fully stand-alone working optical-flow processing system to include both accuracy and speed of measurement of the platform performance. The customisability of the system for different hardware resources and platforms has also been discussed, showing the resources and performance for a stand-alone board and a PCI co-processing board

Verifying Parameterized Networks Using Abstraction and Regular Languages

EM Clarke — 2006-01-31T21:37:23-00:00

pp. 395-407.

ion and Regular Languages ? E. M. Clarke 1 and O. Grumberg 2 and S. Jha 1 1 Carnegie Mellon University, Pittsburgh, PA 15213 2 Computer Science Dept, The Technion, Haifa 32000, Israel Abstract. This paper describes a technique based on network grammars and abstraction to verify families of state-transition systems. The family of state-transition systems is represented by a context-free network grammar. Using the structure of the network grammar our technique constructs an invariant...

Applications of DNA tiling arrays to experimental genome annotation and regulatory pathway discovery

Paul Bertone — 2005-05-06T02:10:50-00:00

Chromosome Research, Vol. 13, No. 3. (January 2005), pp. 259-274.

Applications of DNA tiling arrays for whole-genome analysis.

TC Mockler — 2007-01-23T05:35:26-00:00

Genomics, Vol. 85, No. 1. (January 2005), pp. 1-15.

DNA microarrays are a well-established technology for measuring gene expression levels. Microarrays designed for this purpose use relatively few probes for each gene and are biased toward known and predicted gene structures. Recently, high-density oligonucleotide-based whole-genome microarrays have emerged as a preferred platform for genomic analysis beyond simple gene expression profiling. Potential uses for such whole-genome arrays include empirical annotation of the transcriptome, chromatin-immunoprecipitation-chip studies, analysis of alternative splicing, characterization of the methylome (the methylation state of the genome), polymorphism discovery and genotyping, comparative genome hybridization, and genome resequencing. Here we review different whole-genome microarray designs and applications of this technology to obtain a wide variety of genomic scale information.

Rapid analysis of the DNA-binding specificities of transcription factors with DNA microarrays

Sonali Mukherjee — 2004-12-06T02:31:50-00:00

Nature Genetics, Vol. 36, No. 12. (14 November 2004), 1331.

Micromachined thick permanent magnet arrays on silicon wafers

TM Liakopoulos — 2008-01-02T19:58:10-00:00

Magnetics, IEEE Transactions on, Vol. 32, No. 5. (1996), pp. 5154-5156.

Using micromachining and electroplating techniques, micromachined thick CoNiMnP-based permanent magnet arrays have been designed, fabricated, and characterized for magnetic microelectromechanical systems (MEMS) device applications. The electroplated magnet arrays contain 1,500 magnets of 40 μm×40 μm×50 μm in a cubic shape on the silicon substrate of 2.5 mm×2.5 mm, where the magnets have shown a fairly high magnetic vertical coercivity of 800-1300 Oe, a retentivity of 2.0-3.0 kG, a maximum flux saturation of 12.0-13.0 kG, and a maximum energy density of 14 kJ/m<sup>3</sup>

Advantages of Backward Searching — Efficient Secondary Memory and Distributed Implementation of Compressed Suffix Arrays

Veli Mäkinen — 2008-07-15T15:05:56-00:00

Algorithms and Computation (2005), pp. 681-692.

One of the most relevant succinct suffix array proposals in the literature is the Compressed Suffix Array (CSA) of Sadakane [ISAAC 2000]. The CSA needs n(H0+O(loglog)) bits of space, where n is the text size, is the alphabet size, and H0 the zero-order entropy of the text. The number of occurrences of a pattern of length m can be computed in O(mlog n) time. Most notably, the CSA does not need the text separately available to operate. The CSA simulates a binary search over the suffix array, where the query is compared against text substrings. These are extracted from the same CSA by following irregular access patterns over the structure. Sadakane [SODA 2002] has proposed using backward searching on the CSA in similar fashion as the FM-index of Ferragina and Manzini [FOCS 2000]. He has shown that the CSA can be searched in O(m) time whenever = O(polylog(n)). In this paper we consider some other consequences of backward searching applied to CSA. The most remarkable one is that we do not need, unlike all previous proposals, any complicated sub-linear structures based on the four-Russians technique (such as constant time rank and select queries on bit arrays). We show that sampling and compression are enough to achieve O(mlog n) query time using less space than the original structure. It is also possible to trade structure space for search time. Furthermore, the regular access pattern of backward searching permits an efficient secondary memory implementation, so that the search can be done with O(m logB n) disk accesses, being B the disk block size. Finally, it permits a distributed implementation with optimal speedup and negligible communication effort.

affyGG: Computational protocols for genetical genomics with Affymetrix arrays

Rudi Alberts — 2007-12-18T02:35:51-00:00

Bioinformatics (16 December 2007), btm614.

Motivation: Affymetrix arrays use multiple probes per gene to measure mRNA abundances. Standard software takes averages over probes. Important information may be lost if polymorphisms in the mRNA affect the hybridization of individual probes. Results: We present custom software to analyze genetical genomics experiments in human, mouse and other organisms: (i) an R package providing functions for QTL analysis at the individual probe level, and (ii) Perl scripts providing custom tracks in the UCSC Genome Browser to check for sequence polymorphisms in probe regions. Availability: http://gbic.biol.rug.nl/supplementary. Contact: r.c.jansen@rug.nl 10.1093/bioinformatics/btm614

Expression profiling in primates reveals a rapid evolution of human transcription factors

Yoav Gilad — 2006-03-08T21:24:12-00:00

Nature, Vol. 440, No. 7081. (March 2006), pp. 242-245.

A genotype calling algorithm for affymetrix SNP arrays

Nusrat Rabbee — 2006-01-09T21:51:05-00:00

Bioinformatics, Vol. 22, No. 1. (1 January 2006), pp. 7-12.

Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome

Mark Bieda — 2006-08-03T21:50:49-00:00

Genome Res., Vol. 16, No. 5. (1 May 2006), pp. 595-605.

The E2F family of transcription factors regulates basic cellular processes. Here, we take an unbiased approach towards identifying E2F1 target genes by examining localization of E2F1-binding sites using high-density oligonucleotide tiling arrays. To begin, we developed a statistically-based methodology for analysis of ChIP-chip data obtained from arrays that represent 30 Mb of the human genome. Using this methodology, we identified regions bound by E2F1, MYC, and RNA Polymerase II (POLR2A). We found a large number of binding sites for all three factors; extrapolation suggests there may be [~]20,000-30,000 E2F1- and MYC-binding sites and [~]12,000-17,000 active promoters in HeLa cells. In contrast to our results for MYC, we find that the majority of E2F1-binding sites (>80%) are located in core promoters and that 50% of the sites overlap transcription starts. Only a small fraction of E2F1 sites possess the canonical binding motif. Surprisingly, we found that [~]30% of genes in the 30-Mb region possessed an E2F1 binding site in a core promoter and E2F1 was bound near to 83% of POLR2A-bound sites. To determine if these results were representative of the entire human genome, we performed ChIP-chip analyses of [~]24,000 promoters and confirmed that greater than 20% of the promoters were bound by E2F1. Our results suggest that E2F1 is recruited to promoters via a method distinct from recognition of the known consensus site and point toward a new understanding of E2F1 as a factor that contributes to the regulation of a large fraction of human genes. 10.1101/gr.4887606

A supervised hidden Markov model framework for efficiently segmenting tiling array data in transcriptional and ChIP-chip experiments: systematically incorporating validated biological knowledge.

Jiang Du — 2006-10-23T15:32:54-00:00

Bioinformatics (12 October 2006)

MOTIVATION: Large-scale tiling array experiments are becoming increasingly common in genomics. In particular, the ENCODE project requires the consistent segmentation of many different tiling array data sets into "active regions" (e.g. finding transfrags from transcriptional data and putative binding sites from ChIP-chip experiments). Previously, such segmentation was done in an unsupervised fashion mainly based on characteristics of the signal distribution in the tiling array data itself. Here we propose a supervised framework for doing this. It has the advantage of explicitly incorporating validated biological knowledge into the model and allowing for formal training and testing. Methodology: In particular, we use a hidden Markov model (HMM) framework, which is capable of explicitly modeling the dependency between neighboring probes and whose extended version (the generalized HMM) also allows explicit description of state duration density. We introduce a formal definition of the tiling-array analysis problem, and explain how we can use this to describe sampling small genomic regions for experimental validation to build up a gold-standard set for training and testing. We then describe various ideal and practical sampling strategies (e.g. maximizing signal entropy within a selected region versus using gene annotation or known promoters as positives for transcription or ChIP-chip data, respectively). RESULTS: For the practical sampling and training strategies, we show how the size and noise in the validated training data affects the performance of an HMM applied to the ENCODE transcriptional and ChIP-chip experiments. In particular, we show that the HMM framework is able to efficiently process tiling array data as well as or better than previous approaches. For the idealized sampling strategies, we show how we can assess their performance in a simulation framework and how a maximum entropy approach, which samples sub-regions with very different signal intensities, gives the maximally performing gold-standard. This latter result has strong implications for the optimum way medium-scale validation experiments should be carried out to verify the results of the genome-scale tiling array experiments. SUPPLEMENTARY INFORMATION: The supplementary materials are available at http://tiling.gersteinlab.org/hmm/.

Survival prediction of diffuse large-B-cell lymphoma based on both clinical and gene expression information

Lexin Li — 2006-02-12T21:32:28-00:00

Bioinformatics, Vol. 22, No. 4. (15 February 2006), pp. 466-471.

Microarray gene expression data with linked survival phenotypes: diffuse large-B-cell lymphoma revisited

Segal — 2006-03-30T04:09:26-00:00

Biostatistics, Vol. 7, No. 2. (April 2006), pp. 268-285.

Hybrid hierarchical clustering with applications to microarray data

Chipman — 2006-03-30T04:09:26-00:00

Biostatistics, Vol. 7, No. 2. (April 2006), pp. 286-301.

Genome-Wide Detection of Polymorphisms at Nucleotide Resolution with a Single DNA Microarray

David Gresham — 2006-03-31T07:56:05-00:00

Science, Vol. 311, No. 5769. (31 March 2006), pp. 1932-1936.

A central challenge of genomics is to detect, simply and inexpensively, all differences in sequence among the genomes of individual members of a species. We devised a system to detect all single-nucleotide differences between genomes with the use of data from a single hybridization to a whole-genome DNA microarray. This allowed us to detect a variety of spontaneous single-base pair substitutions, insertions, and deletions, and most (>90%) of the [~]30,000 known single-nucleotide polymorphisms between two Saccharomyces cerevisiae strains. We applied this approach to elucidate the genetic basis of phenotypic variants and to identify the small number of single-base pair changes accumulated during experimental evolution of yeast. 10.1126/science.1123726

ITALICS: an algorithm for normalization and DNA copy number calling for Affymetrix SNP arrays

Guillem Rigaill — 2008-03-13T16:40:36-00:00

Bioinformatics, Vol. 24, No. 6. (15 March 2008), pp. 768-774.

Motivation: Affymetrix SNP arrays can be used to determine the DNA copy number measurement of 11 000500 000 SNPs along the genome. Their high density facilitates the precise localization of genomic alterations and makes them a powerful tool for studies of cancers and copy number polymorphism. Like other microarray technologies it is influenced by non-relevant sources of variation, requiring correction. Moreover, the amplitude of variation induced by non-relevant effects is similar or greater than the biologically relevant effect (i.e. true copy number), making it difficult to estimate non-relevant effects accurately without including the biologically relevant effect. Results: We addressed this problem by developing ITALICS, a normalization method that estimates both biological and non-relevant effects in an alternate, iterative manner, accurately eliminating irrelevant effects. We compared our normalization method with other existing and available methods, and found that ITALICS outperformed these methods for several in-house datasets and one public dataset. These results were validated biologically by quantitative PCR. Availability: The R package ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) has been submitted to Bioconductor. Contact: italics@curie.fr Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btn048

Estimation and assessment of raw copy numbers at the single locus level

H Bengtsson — 2008-03-13T16:39:53-00:00

Bioinformatics, Vol. 24, No. 6. (15 March 2008), pp. 759-767.

Motivation: Although copy-number aberrations are known to contribute to the diversity of the human DNA and cause various diseases, many aberrations and their phenotypes are still to be explored. The recent development of single-nucleotide polymorphism (SNP) arrays provides researchers with tools for calling genotypes and identifying chromosomal aberrations at an order-of-magnitude greater resolution than possible a few years ago. The fundamental problem in array-based copy-number (CN) analysis is to obtain CN estimates at a single-locus resolution with high accuracy and precision such that downstream segmentation methods are more likely to succeed. Results: We propose a preprocessing method for estimating raw CNs from Affymetrix SNP arrays. Its core utilizes a multichip probe-level model analogous to that for high-density oligonucleotide expression arrays. We extend this model by adding an adjustment for sequence-specific allelic imbalances such as cross-hybridization between allele A and allele B probes. We focus on total CN estimates, which allows us to further constrain the probe-level model to increase the signal-to-noise ratio of CN estimates. Further improvement is obtained by controlling for PCR effects. Each part of the model is fitted robustly. The performance is assessed by quantifying how well raw CNs alone differentiate between one and two copies on Chromosome X (ChrX) at a single-locus resolution (27kb) up to a 200kb resolution. The evaluation is done with publicly available HapMap data. Availability: The proposed method is available as part of an open-source R package named aroma.affymetrix. Because it is a bounded-memory algorithm, any number of arrays can be analyzed. Contact: hb@stat.berkeley.edu Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btn016

Extensions to gene set enrichment

Zhen Jiang — 2007-02-02T17:42:27-00:00

Bioinformatics, Vol. 23, No. 3. (1 February 2007), pp. 306-313.

Motivation: Gene Set Enrichment Analysis (GSEA) has been developed recently to capture changes in the expression of pre-defined sets of genes. We propose number of extensions to GSEA, including the use of different statistics to describe the association between genes and phenotypes of interest. We make use of dimension reduction procedures, such as principle component analysis, to identify gene sets with correlated expression. We also address issues that arise when gene sets overlap. Results: Our proposals extend the range of applicability of GSEA and allow for adjustments based on other covariates. We have provided a well-defined procedure to address interpretation issues that can raise when gene sets have substantial overlap. We have shown how standard dimension reduction methods, such as PCA, can be used to help further interpret GSEA. Contact: zjiang@fhcrc.org Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btl599

The ENCODE (ENCyclopedia Of DNA Elements) Project.

2005-04-04T06:53:10-00:00

Science, Vol. 306, No. 5696. (22 October 2004), pp. 636-640.

The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (approximately 1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

Biological function of unannotated transcription during the early development of Drosophila melanogaster

Robert Manak — 2006-09-28T09:22:15-00:00

Nature Genetics, Vol. 38, No. 10. (03 September 2006), pp. 1151-1158.

Time ordering of gene coexpression

Xiaoyan Leng — 2006-09-28T17:22:14-00:00

Biostat, Vol. 7, No. 4. (1 October 2006), pp. 569-584.

Temporal microarray gene expression profiles allow characterization of gene function through time dynamics of gene coexpression within the same genetic pathway. In this paper, we define and estimate a global time shift characteristic for each gene via least squares, inferred from pairwise curve alignments. These time shift characteristics of individual genes reflect a time ordering that is derived from ob- served temporal gene expression profiles. Once these time shift characteristics are obtained for each gene, they can be entered into further analyses, such as clustering. We illustrate the proposed methodology using Drosophila embryonic development and yeast cell-cycle gene expression profiles, as well as simulations. Feasibility is demonstrated through the successful recovery of time ordering. Estimated time shifts for Drosophila maternal and zygotic genes provide excellent discrimination between these two categories and confirm known genetic pathways through the time order of gene expression. The application to yeast cell-cycle data establishes a natural time order of genes that is in line with cell-cycle phases. The method does not require periodicity of gene expression profiles. Asymptotic justifications are also provided. 10.1093/biostatistics/kxj026

On grating nulls in adaptive arrays

A Ishide — 2008-02-24T13:35:57-00:00

Antennas and Propagation, IEEE Transactions on [legacy, pre - 1988], Vol. 28, No. 4. (1980), pp. 467-475.

The effect of element patterns on grating nulls in adaptive arrays is considered. Two simple array models, a two-element and a three-element array with dipole element patterns, are used to study this question. The element patterns are assumed unequal (i.e., the beam maxima point in different directions). It is shown that element patterns greatly affect the occurrence of grating nulls in the array. Unequal element patterns cause extra grating nulls ("sign reversal grating nulls") to occur, in addition to conventional grating nulls. These sign reversal grating nulls can occur even with element spacing less than a half-wavelength. For a two-element array with dipole element patterns, it turns out that grating nulls cannot be avoided if the spacing is greater than a half-wavelength. However, with more than two elements, the situation is not so bleak. An example is given of a three-element array with dipole patterns and one-wavelength spacing in which all grating nulls are eliminated.

Purely Functional Random-Access Lists

Chris Okasaki — 2007-11-19T17:17:31-00:00

(1995), pp. 86-95.

We present a new data structure, called a random-access list, that supports array lookup and update operations in O(log n) time, while simultaneously providing O(1) time list operations (cons, head, tail). A closer analysis of the array operations improves the bound to O(minfi; log ng) in the worst case and O(log i) in the expected case, where i is the index of the desired element. Empirical evidence suggests that this data structure should be quite efficient in practice. 1 Introduction...

Bootstrapping One-sided Flexible Arrays

Ralf Hinze — 2005-10-19T04:25:37-00:00

The abstract data type one-sided flexible array, also called randomaccess list, supports look-up and update of elements and can grow and shrink at one end. We describe a purely functional implementation based on weight-balanced multiway trees that is both simple and versatile. A novel feature of the representation is that the running time of the operations can be tailored to one's needs---even dynamically at array-creation time. In particular, one can trade the running time of look-up...

Low-loss fiber accessible plasmon waveguide for planar energy guiding and sensing

Stefan Maier — 2008-07-03T07:15:10-00:00

Applied Physics Letters, Vol. 84, No. 20. (2004), pp. 3990-3992.

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