Comparison of sequence-dependent tiling array normalization approaches

Background  

The detection of enriched DNA or RNA fragments by tiling microarrays has become more and more popular. These microarrays contain a high number of small probes covering genomic loci. However, to achieve high coverage the probe sequences cannot be selected for their hybridization properties. The affinity of the probes towards their targets varies in a sequence-dependent manner. In order to remove this bias a number of approaches have been developed and shown to increase the detection of enriched DNA or RNA fragments. However, these approaches also employ a peak detection algorithm that is different from the one used previously. Thus, it seems possible that the enhancement of detection is due to the peak detection algorithm rather than the sequence-dependent normalization.     

An automatic method for identifying surface proteins in bacteria: SLEP

Background  

Bacterial infections represent a global health challenge. The identification of novel antibacterial targets for both therapy and vaccination is needed on a constant basis because resistance continues to spread worldwide at an alarming rate. Even infections that were once easy to treat are becoming difficult or, in some cases, impossible to cure. Ideal targets for both therapy and vaccination are bacterial proteins exposed on the surface of the organism, which are often involved in host-pathogen interaction. Their identification can greatly benefit from technologies such as bioinformatics, proteomics and DNA microarrays.     

Validation and characterization of DNA microarray gene expression data distribution and associated moments

Background  

The data from DNA microarrays are increasingly being used in order to understand effects of different conditions, exposures or diseases on the modulation of the expression of various genes in a biological system. This knowledge is then further used in order to generate molecular mechanistic hypotheses for an organism when it is exposed to different conditions. Several different methods have been proposed to analyze these data under different distributional assumptions on gene expression. However, the empirical validation of these assumptions is lacking.     

CrossHybDetector: detection of cross-hybridization events in DNA microarray experiments

Background  

DNA microarrays contain thousands of different probe sequences represented on their surface. These are designed in such a way that potential cross-hybridization reactions with non-target sequences are minimized. However, given the large number of probes, the occurrence of cross hybridization events cannot be excluded. This problem can dramatically affect the data quality and cause false positive/false negative results.     

M<Superscript>3</Superscript>G: Maximum Margin Microarray Gridding

Background  

Complementary DNA (cDNA) microarrays are a well established technology for studying gene expression. A microarray image is obtained by laser scanning a hybridized cDNA microarray, which consists of thousands of spots representing chains of cDNA sequences, arranged in a two-dimensional array. The separation of the spots into distinct cells is widely known as microarray image gridding.     

MCALIGN2: Faster, accurate global pairwise alignment of non-coding DNA sequences based on explicit models of indel evolution

Background  

Non-coding DNA sequences comprise a very large proportion of the total genomic content of mammals, most other vertebrates, many invertebrates, and most plants. Unraveling the functional significance of non-coding DNA depends on how well we are able to align non-coding DNA sequences. However, the alignment of non-coding DNA sequences is more difficult than aligning protein-coding sequences.     

Reduced stability of mRNA secondary structure near the translation-initiation site in dsDNA viruses

Background  

Recent studies have demonstrated a selection pressure for reduced mRNA secondary-structure stability near the start codon of coding sequences. This selection pressure can be observed in bacteria, archaea, and eukaryotes, and is likely caused by the requirement of efficient translation initiation in cellular organism.     

transAlign: using amino acids to facilitate the multiple alignment of protein-coding DNA sequences

Background  

Alignments of homologous DNA sequences are crucial for comparative genomics and phylogenetic analysis. However, multiple alignment represents a computationally difficult problem. For protein-coding DNA sequences, it is more advantageous in terms of both speed and accuracy to align the amino-acid sequences specified by the DNA sequences rather than the DNA sequences themselves. Many implementations making use of this concept of "translated alignments" are incomplete in the sense that they require the user to manually translate the DNA sequences and to perform the amino-acid alignment. As such, they are not well suited to large-scale automated alignments of large and/or numerous DNA data sets.     

GCOD - GeneChip Oncology Database

Background  

DNA microarrays have become a nearly ubiquitous tool for the study of human disease, and nowhere is this more true than in cancer. With hundreds of studies and thousands of expression profiles representing the majority of human cancers completed and in public databases, the challenge has been effectively accessing and using this wealth of data.     

Fungal-specific PCR primers developed for analysis of the ITS region of environmental DNA extracts

Background  

The Internal Transcribed Spacer (ITS) regions of fungal ribosomal DNA (rDNA) are highly variable sequences of great importance in distinguishing fungal species by PCR analysis. Previously published PCR primers available for amplifying these sequences from environmental samples provide varying degrees of success at discriminating against plant DNA while maintaining a broad range of compatibility. Typically, it has been necessary to use multiple primer sets to accommodate the range of fungi under study, potentially creating artificial distinctions for fungal sequences that amplify with more than one primer set.     

DNA microarray data and contextual analysis of correlation graphs

Background  

DNA microarrays are used to produce large sets of expression measurements from which specific biological information is sought. Their analysis requires efficient and reliable algorithms for dimensional reduction, classification and annotation.     

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.     

Checkpoint effects and telomere amplification during DNA re-replication in fission yeast

Background  

Although much is known about molecular mechanisms that prevent re-initiation of DNA replication on newly replicated DNA during a single cell cycle, knowledge is sparse regarding the regions that are most susceptible to re-replication when those mechanisms are bypassed and regarding the extents to which checkpoint pathways modulate re-replication. We used microarrays to learn more about these issues in wild-type and checkpoint-mutant cells of the fission yeast, Schizosaccharomyces pombe.     

Bayesian modeling of recombination events in bacterial populations

Background  

We consider the discovery of recombinant segments jointly with their origins within multilocus DNA sequences from bacteria representing heterogeneous populations of fairly closely related species. The currently available methods for recombination detection capable of probabilistic characterization of uncertainty have a limited applicability in practice as the number of strains in a data set increases.     

The IronChip evaluation package: a package of perl modules for robust analysis of custom microarrays

Background  

Gene expression studies greatly contribute to our understanding of complex relationships in gene regulatory networks. However, the complexity of array design, production and manipulations are limiting factors, affecting data quality. The use of customized DNA microarrays improves overall data quality in many situations, however, only if for these specifically designed microarrays analysis tools are available.     

Microarray-based method for detection of unknown genetic modifications

Background  

Due to the increased use of genetic modifications in crop improvement, there is a need to develop effective methods for the detection of both known and unknown transgene constructs in plants. We have developed a strategy for detection and characterization of unknown genetic modifications and we present a proof of concept for this method using Arabidopsis thaliana and Oryza sativa (rice). The approach relies on direct hybridization of total genomic DNA to high density microarrays designed to have probes tiled throughout a set of reference sequences.