Biomedical subjects

Rasmus Wernersson

Publications and source records attributed to Rasmus Wernersson.

9 recordsLinked to original sources

PubMed2006

An overabundance of phase 0 introns immediately after the start codon in eukaryotic genes.

BACKGROUND: A knowledge of the positions of introns in eukaryotic genes is important for understanding the evolution of introns. Despite this, there has been relatively little focus on the distribution of intron positions in genes. RESULTS: In proteins with signal peptides, there is an overabundance of phase 1 introns around the region of the signal peptide cleavage site. This has been described before. But in proteins without signal peptides, a novel phenomenon is observed: There is a sharp peak of phase 0 intron positions immediately following the start codon, i.e. between codons 1 and 2. This effect is seen in a wide range of eukaryotes: Vertebrates, arthropods, fungi, and flowering plants. Proteins carrying this start codon intron are found to comprise a special class of relatively short, lysine-rich and conserved proteins with an overrepresentation of ribosomal proteins. In addition, there is a peak of phase 0 introns at position 5 in Drosophila genes with signal peptides, predominantly representing cuticle proteins. CONCLUSION: There is an overabundance of phase 0 introns immediately after the start codon in eukaryotic genes, which has been described before only for human ribosomal proteins. We give a detailed description of these start codon introns and the proteins that contain them.

Animals↗

PubMed2006

FeatureMap3D--a tool to map protein features and sequence conservation onto homologous structures in the PDB.

FeatureMap3D is a web-based tool that maps protein features onto 3D structures. The user provides sequences annotated with any feature of interest, such as post-translational modifications, protease cleavage sites or exonic structure and FeatureMap3D will then search the Protein Data Bank (PDB) for structures of homologous proteins. The results are displayed both as an annotated sequence alignment, where the user-provided annotations as well as the sequence conservation between the query and the target sequence are displayed, and also as a publication-quality image of the 3D protein structure with the selected features and sequence conservation enhanced. The results are also returned in a readily parsable text format as well as a PyMol (http://pymol.sourceforge.net/) script file, which allows the user to easily modify the protein structure image to suit a specific purpose. FeatureMap3D can also be used without sequence annotation, to evaluate the quality of the alignment of the input sequences to the most homologous structures in the PDB, through the sequence conservation colored 3D structure visualization tool. FeatureMap3D is available at: http://www.cbs.dtu.dk/services/FeatureMap3D/.

Amino Acid Sequence↗

PubMed2006

Virtual Ribosome--a comprehensive DNA translation tool with support for integration of sequence feature annotation.

Virtual Ribosome is a DNA translation tool with two areas of focus. (i) Providing a strong translation tool in its own right, with an integrated ORF finder, full support for the IUPAC degenerate DNA alphabet and all translation tables defined by the NCBI taxonomy group, including the use of alternative start codons. (ii) Integration of sequences feature annotation--in particular, native support for working with files containing intron/exon structure annotation. The software is available for both download and online use at http://www.cbs.dtu.dk/services/VirtualRibosome/.

Animals↗

PubMed2005

FeatureExtract--extraction of sequence annotation made easy.

Work on a large number of biological problems benefits tremendously from having an easy way to access the annotation of DNA sequence features, such as intron/exon structure, the contents of promoter regions and the location of other genes in upsteam and downstream regions. For example, taking the placement of introns within a gene into account can help in a phylogenetic analysis of homologous genes. Designing experiments for investigating UTR regions using PCR or DNA microarrays require knowledge of known elements in UTR regions and the positions and strandness of other genes nearby on the chromosome. A wealth of such information is already known and documented in databases such as GenBank and the NCBI Human Genome builds. However, it usually requires significant bioinformatics skills and intimate knowledge of the data format to access this information. Presented here is a highly flexible and easy-to-use tool for extracting feature annotation from GenBank entries. The tool is also useful for extracting datasets corresponding to a particular feature (e.g. promoters). Most importantly, the output data format is highly consistent, easy to handle for the user and easy to parse computationally. The FeatureExtract web server is freely available for both academic and commercial use at http://www.cbs.dtu.dk/services/FeatureExtract/.

Chromosomes↗

PubMed2005

OligoWiz 2.0--integrating sequence feature annotation into the design of microarray probes.

OligoWiz 2.0 is a powerful tool for microarray probe design that allows for integration of sequence annotation, such as exon/intron structure, untranslated regions (UTRs), transcription start site, etc. In addition to probe selection according to a series of probe quality parameters, cross-hybridization, T(m), position in transcript, probe folding and low-complexity, the program facilitates automatic placement of probes relative to the sequence annotation. The program also supports automatic placement of multiple probes per transcript. Together these facilities make advanced probe design feasible for scientists inexperienced in computerized information management. Furthermore, we show that probes designed using OligoWiz 2.0 give rise to consistent hybridization results (http://www.cbs.dtu.dk/services/OligoWiz2).

Algorithms↗

PubMed2005

Pigs in sequence space: a 0.66X coverage pig genome survey based on shotgun sequencing.

BACKGROUND: Comparative whole genome analysis of Mammalia can benefit from the addition of more species. The pig is an obvious choice due to its economic and medical importance as well as its evolutionary position in the artiodactyls. RESULTS: We have generated approximately 3.84 million shotgun sequences (0.66X coverage) from the pig genome. The data are hereby released (NCBI Trace repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project") together with an initial evolutionary analysis. The non-repetitive fraction of the sequences was aligned to the UCSC human-mouse alignment and the resulting three-species alignments were annotated using the human genome annotation. Ultra-conserved elements and miRNAs were identified. The results show that for each of these types of orthologous data, pig is much closer to human than mouse is. Purifying selection has been more efficient in pig compared to human, but not as efficient as in mouse, and pig seems to have an isochore structure most similar to the structure in human. CONCLUSION: The addition of the pig to the set of species sequenced at low coverage adds to the understanding of selective pressures that have acted on the human genome by bisecting the evolutionary branch between human and mouse with the mouse branch being approximately 3 times as long as the human branch. Additionally, the joint alignment of the shot-gun sequences to the human-mouse alignment offers the investigator a rapid way to defining specific regions for analysis and resequencing.

Animals↗

PubMed2005

New weakly expressed cell cycle-regulated genes in yeast.

We present an approach combining bioinformatics prediction with experimental microarray validation to identify new cell cycle-regulated genes in Saccharomyces cerevisiae. We identify in the order of 100 new cell cycle-regulated genes and show by independent data that these genes in general tend to be more weakly expressed than the genes identified hitherto. Among the genes not previously suggested to be periodically expressed we find genes linked to DNA repair, cell size monitoring and transcriptional control, as well as a number of genes of unknown function. Several of the gene products are believed to be phosphorylated by Cdc28. For many of these new genes, homologues exist in Schizosaccharomyces pombe and Homo sapiens for which the expression also varies with cell cycle progression.

Cell Cycle Proteins↗

PubMed2003

RevTrans: Multiple alignment of coding DNA from aligned amino acid sequences.

The simple fact that proteins are built from 20 amino acids while DNA only contains four different bases, means that the 'signal-to-noise ratio' in protein sequence alignments is much better than in alignments of DNA. Besides this information-theoretical advantage, protein alignments also benefit from the information that is implicit in empirical substitution matrices such as BLOSUM-62. Taken together with the generally higher rate of synonymous mutations over non-synonymous ones, this means that the phylogenetic signal disappears much more rapidly from DNA sequences than from the encoded proteins. It is therefore preferable to align coding DNA at the amino acid level and it is for this purpose we have constructed the program RevTrans. RevTrans constructs a multiple DNA alignment by: (i) translating the DNA; (ii) aligning the resulting peptide sequences; and (iii) building a multiple DNA alignment by 'reverse translation' of the aligned protein sequences. In the resulting DNA alignment, gaps occur in groups of three corresponding to entire codons, and analogous codon positions are therefore always lined up. These features are useful when constructing multiple DNA alignments for phylogenetic analysis. RevTrans also accepts user-provided protein alignments for greater control of the alignment process. The RevTrans web server is freely available at http://www.cbs.dtu.dk/services/RevTrans/.

Amino Acid Substitution↗

PubMed2003

Design of oligonucleotides for microarrays and perspectives for design of multi-transcriptome arrays.

Optimal design of oligonucleotides for microarrays involves tedious and laborious work evaluating potential oligonucleotides relative to a series of parameters. The currently available tools for this purpose are limited in their flexibility and do not present the oligonucleotide designer with an overview of these parameters. We present here a flexible tool named OligoWiz for designing oligonucleotides for multiple purposes. OligoWiz presents a set of parameter scores in a graphical interface to facilitate an overview for the user. Additional custom parameter scores can easily be added to the program to extend the default parameters: homology, DeltaTm, low-complexity, position and GATC-only. Furthermore we present an analysis of the limitations in designing oligonucleotide sets that can detect transcripts from multiple organisms. OligoWiz is available at www.cbs.dtu.dk/services/OligoWiz/.

DNA Primers↗