Efficient oligonucleotide probe selection for pan-genomic tiling arrays

Background  

Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome.     

Mutational pattern and frequency of induced nucleotide changes in mouse ENU mutagenesis

Background  

With the advent of sequence-based approaches in the mutagenesis studies, it is now possible to directly evaluate the genome-wide pattern of experimentally induced DNA sequence changes for a diverse array of organisms. To gain a more comprehensive understanding of the mutational bias inherent in mouse ENU mutagenesis, this study describes a detailed evaluation of the induced mutational pattern obtained from a sequence-based screen of ENU-mutagenized mice.     

Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

Background  

Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance) between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%), suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed.     

Mathematical design of prokaryotic clone-based microarrays

Background  

Clone-based microarrays, on which each spot represents a random genomic fragment, are a good alternative to open reading frame-based microarrays, especially for microorganisms for which the complete genome sequence is not available. Since the generation of a genomic DNA library is a random process, it is beforehand uncertain which genes are represented. Nevertheless, the genome coverage of such an array, which depends on different variables like the insert size and the number of clones in the library, can be predicted by mathematical approaches. When applying the classical formulas that determine the probability that a certain sequence is represented in a DNA library at the nucleotide level, massive amounts of clones would be necessary to obtain a proper coverage of the genome.     

MIMAS 3.0 is a Multiomics Information Management and Annotation System

Background  

DNA sequence integrity, mRNA concentrations and protein-DNA interactions have been subject to genome-wide analyses based on microarrays with ever increasing efficiency and reliability over the past fifteen years. However, very recently novel technologies for Ultra High-Throughput DNA Sequencing (UHTS) have been harnessed to study these phenomena with unprecedented precision. As a consequence, the extensive bioinformatics environment available for array data management, analysis, interpretation and publication must be extended to include these novel sequencing data types.     

Conservation and divergence of ADAM family proteins in the <Emphasis Type="Italic">Xenopus</Emphasis> genome

Background  

Members of the disintegrin metalloproteinase (ADAM) family play important roles in cellular and developmental processes through their functions as proteases and/or binding partners for other proteins. The amphibian Xenopus has long been used as a model for early vertebrate development, but genome-wide analyses for large gene families were not possible until the recent completion of the X. tropicalis genome sequence and the availability of large scale expression sequence tag (EST) databases. In this study we carried out a systematic analysis of the X. tropicalis genome and uncovered several interesting features of ADAM genes in this species.     

Serial evolutionary networks of within-patient HIV-1 sequences reveal patterns of evolution of X4 strains

Background  

The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation of the mutational pathways of a viral population in a within-host environment. The longitudinal representation of the evolutionary networks was complemented with charts of clinical markers to facilitate correlation analysis between pertinent clinical information and the evolutionary relationships.     

A proposed metric for assessing the measurement quality of individual microarrays

Background  

High-density microarray technology is increasingly applied to study gene expression levels on a large scale. Microarray experiments rely on several critical steps that may introduce error and uncertainty in analyses. These steps include mRNA sample extraction, amplification and labeling, hybridization, and scanning. In some cases this may be manifested as systematic spatial variation on the surface of microarray in which expression measurements within an individual array may vary as a function of geographic position on the array surface.     

Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease

Background  

X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions.     

Correlation test to assess low-level processing of high-density oligonucleotide microarray data

Background  

There are currently a number of competing techniques for low-level processing of oligonucleotide array data. The choice of technique has a profound effect on subsequent statistical analyses, but there is no method to assess whether a particular technique is appropriate for a specific data set, without reference to external data.     

M-CGH: Analysing microarray-based CGH experiments

Background  

Microarray-based comparative genomic hybridisation (array CGH) is a technique by which variation in relative copy numbers between two genomes can be analysed by competitive hybridisation to DNA microarrays. This technology has most commonly been used to detect chromosomal amplifications and deletions in cancer. Dedicated tools are needed to analyse the results of such experiments, which include appropriate visualisation, and to take into consideration the physical relation in the genome between the probes on the array.     

WAMI: a web server for the analysis of minisatellite maps

Background  

Minisatellites are genomic loci composed of tandem arrays of short repetitive DNA segments. A minisatellite map is a sequence of symbols that represents the tandem repeat array such that the set of symbols is in one-to-one correspondence with the set of distinct repeats. Due to variations in repeat type and organization as well as copy number, the minisatellite maps have been widely used in forensic and population studies. In either domain, researchers need to compare the set of maps to each other, to build phylogenetic trees, to spot structural variations, and to study duplication dynamics. Efficient algorithms for these tasks are required to carry them out reliably and in reasonable time.     

Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic

Background  

X chromosome inactivation is a spectacular example of epigenetic silencing. In order to deduce how this complex system evolved, we examined X inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In marsupials, X inactivation is known to be paternal, incomplete and tissue-specific, and occurs in the absence of an XIST orthologue.     

Non-imprinted allele-specific DNA methylation on human autosomes

Background  

Differential DNA methylation between alleles is well established in imprinted genes and the X chromosomes in females but has rarely been reported at non-imprinted loci on autosomes.     

Tiling array data analysis: a multiscale approach using wavelets

Background  

Tiling array data is hard to interpret due to noise. The wavelet transformation is a widely used technique in signal processing for elucidating the true signal from noisy data. Consequently, we attempted to denoise representative tiling array datasets for ChIP-chip experiments using wavelets. In doing this, we used specific wavelet basis functions, Coiflets, since their triangular shape closely resembles the expected profiles of true ChIP-chip peaks.     

CGHpower: exploring sample size calculations for chromosomal copy number experiments

Background  

Determining a suitable sample size is an important step in the planning of microarray experiments. Increasing the number of arrays gives more statistical power, but adds to the total cost of the experiment. Several approaches for sample size determination have been developed for expression array studies, but so far none has been proposed for array comparative genomic hybridization (aCGH).     

Enhanced Bayesian modelling in BAPS software for learning genetic structures of populations

Background  

During the most recent decade many Bayesian statistical models and software for answering questions related to the genetic structure underlying population samples have appeared in the scientific literature. Most of these methods utilize molecular markers for the inferences, while some are also capable of handling DNA sequence data. In a number of earlier works, we have introduced an array of statistical methods for population genetic inference that are implemented in the software BAPS. However, the complexity of biological problems related to genetic structure analysis keeps increasing such that in many cases the current methods may provide either inappropriate or insufficient solutions.     

SeeGH – A software tool for visualization of whole genome array comparative genomic hybridization data

Background  

Array comparative genomic hybridization (CGH) is a technique which detects copy number differences in DNA segments. Complete sequencing of the human genome and the development of an array representing a tiling set of tens of thousands of DNA segments spanning the entire human genome has made high resolution copy number analysis throughout the genome possible. Since array CGH provides signal ratio for each DNA segment, visualization would require the reassembly of individual data points into chromosome profiles.     

Independent component analysis reveals new and biologically significant structures in micro array data

Background  

An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS) problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes.     

Recovery and evolutionary analysis of complete integron gene cassette arrays from Vibrio

Background  

Integrons are genetic elements capable of the acquisition, rearrangement and expression of genes contained in gene cassettes. Gene cassettes generally consist of a promoterless gene associated with a recombination site known as a 59-base element (59-be). Multiple insertion events can lead to the assembly of large integron-associated cassette arrays. The most striking examples are found in Vibrio, where such cassette arrays are widespread and can range from 30 kb to 150 kb. Besides those found in completely sequenced genomes, no such array has yet been recovered in its entirety. We describe an approach to systematically isolate, sequence and annotate large integron gene cassette arrays from bacterial strains.