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At least 325 records · Page 18Linked to original sources
PubMed2002

Visualizing the genome: techniques for presenting human genome data and annotations.

BACKGROUND: In order to take full advantage of the newly available public human genome sequence data and associated annotations, biologists require visualization tools ("genome browsers") that can accommodate the high frequency of alternative splicing in human genes and other complexities. RESULTS: In this article, we describe visualization techniques for presenting human genomic sequence data and annotations in an interactive, graphical format. These techniques include: one-dimensional, semantic zooming to show sequence data alongside gene structures; color-coding exons to indicate frame of translation; adjustable, moveable tiers to permit easier inspection of a genomic scene; and display of protein annotations alongside gene structures to show how alternative splicing impacts protein structure and function. These techniques are illustrated using examples from two genome browser applications: the Neomorphic GeneViewer annotation tool and ProtAnnot, a prototype viewer which shows protein annotations in the context of genomic sequence. CONCLUSION: By presenting techniques for visualizing genomic data, we hope to provide interested software developers with a guide to what features are most likely to meet the needs of biologists as they seek to make sense of the rapidly expanding body of public genomic data and annotations.

Alternative Splicing↗
PubMed2006

XRate: a fast prototyping, training and annotation tool for phylo-grammars.

BACKGROUND: Recent years have seen the emergence of genome annotation methods based on the phylo-grammar, a probabilistic model combining continuous-time Markov chains and stochastic grammars. Previously, phylo-grammars have required considerable effort to implement, limiting their adoption by computational biologists. RESULTS: We have developed an open source software tool, xrate, for working with reversible, irreversible or parametric substitution models combined with stochastic context-free grammars. xrate efficiently estimates maximum-likelihood parameters and phylogenetic trees using a novel "phylo-EM" algorithm that we describe. The grammar is specified in an external configuration file, allowing users to design new grammars, estimate rate parameters from training data and annotate multiple sequence alignments without the need to recompile code from source. We have used xrate to measure codon substitution rates and predict protein and RNA secondary structures. CONCLUSION: Our results demonstrate that xrate estimates biologically meaningful rates and makes predictions whose accuracy is comparable to that of more specialized tools.

Algorithms↗
PubMed2004

The mouse genome: experimental examination of gene predictions and transcriptional start sites.

The completion of the mouse and other mammalian genome sequences will provide necessary, but not sufficient, knowledge for an understanding of much of mouse biology at the molecular level. As a requisite next step in this process, the genes in mouse and their structure must be elucidated. In particular, knowledge of the transcriptional start site of these genes will be necessary for further study of their regulatory regions. To assess the current state of mouse genome annotation to support this activity, we identified several hundred gene predictions in mouse with varying levels of supporting evidence and tested them using RACE-PCR. Modifications were made to the procedure allowing pooling of RNA samples, resulting in a scaleable procedure. The results illustrate potential errors or omissions in the current 5' end annotations in 58% of the genes detected. In testing experimentally unsupported gene predictions, we were able to identify 58 that are not usually annotated as genes but produced spliced transcripts (approximately 25% success rate). In addition, in many genes we were able to detect novel exons not predicted by any gene prediction algorithms. In 19.8% of the genes detected in this study, multiple transcript species were observed. These data show an urgent need to provide direct experimental validation of gene annotations. Moreover, these results show that direct validation using RACE-PCR can be an important component of genome-wide validation. This approach can be a useful tool in the ongoing efforts to increase the quality of gene annotations, especially transcriptional start sites, in complex genomes.

Animals↗
PubMed2001

Regulation of gene expression in flux balance models of metabolism.

Genome-scale metabolic networks can now be reconstructed based on annotated genomic data augmented with biochemical and physiological information about the organism. Mathematical analysis can be performed to assess the capabilities of these reconstructed networks. The constraints-based framework, with flux balance analysis (FBA), has been used successfully to predict time course of growth and by-product secretion, effects of mutation and knock-outs, and gene expression profiles. However, FBA leads to incorrect predictions in situations where regulatory effects are a dominant influence on the behavior of the organism. Thus, there is a need to include regulatory events within FBA to broaden its scope and predictive capabilities. Here we represent transcriptional regulatory events as time-dependent constraints on the capabilities of a reconstructed metabolic network to further constrain the space of possible network functions. Using a simplified metabolic/regulatory network, growth is simulated under various conditions to illustrate systemic effects such as catabolite repression, the aerobic/anaerobic diauxic shift and amino acid biosynthesis pathway repression. The incorporation of transcriptional regulatory events in FBA enables us to interpret, analyse and predict the effects of transcriptional regulation on cellular metabolism at the systemic level.

Amino Acids↗
PubMed2005

Genetic manipulations to study reproduction.

Fertility disorders affect approximately 15% of individuals worldwide. With the imminent completion of the human and mouse genome sequence, it will be more feasible to identify the relevant genes underlying many fertility disorders. Already, the mouse has been utilized extensively as a genetic tool for the dissection of gene function, often providing significant insights into the relationship between gene and disease. In fact, there are over 200 mouse models that display reproductive defects. However, the available mouse mutant resources provide functional information for a mere 10% of the total number of genes in the mouse or human genomes at best. The improvement of available genome annotations together with more powerful techniques to manipulate the mouse genome provide substantial improvements in our ability to identify genes involved in reproduction, and in the future will likely benefit patients with fertility problems.

Animals↗
PubMedDate not supplied

Experiments in searching small proteins in unannotated large eukaryotic genomes.

There is growing interest to use mass spectrometry data to search genome sequences directly. Previous work by other authors demonstrated that this approach is able to correct and complement available genome annotations. We discuss the practical difficulty of searching large eukaryotic genomes with peptide ion trap tandem mass spectra of small proteins (<40 kDa). The challenging problem of automatically identifying peptides that span across exon/intron boundaries is explored for the first time by using experimental data. In a human genome search, we find that roughly 30% of the peptides are missed, due to various reasons, compared to a Swiss-Prot search. We show that this percentage is significantly reduced with improved parent mass accuracy. We finally provide several examples of predicted gene structures that could be improved by proteomics data, in particular by peptides spanning across exon/intron boundaries.

Adult↗
PubMed2004

Computational gene prediction using multiple sources of evidence.

This article describes a computational method to construct gene models by using evidence generated from a diverse set of sources, including those typical of a genome annotation pipeline. The program, called Combiner, takes as input a genomic sequence and the locations of gene predictions from ab initio gene finders, protein sequence alignments, expressed sequence tag and cDNA alignments, splice site predictions, and other evidence. Three different algorithms for combining evidence in the Combiner were implemented and tested on 1783 confirmed genes in Arabidopsis thaliana. Our results show that combining gene prediction evidence consistently outperforms even the best individual gene finder and, in some cases, can produce dramatic improvements in sensitivity and specificity.

Arabidopsis↗
PubMed2026

Auditing bacterial dark-gene screens for superimposed open reading frame artefacts: A multi-layer analysis of Rv2438A in Mycobacterium tuberculosis.

Essentiality and knockdown-vulnerability screens can promote spurious bacterial open reading frames when those frames overlap essential genes, because such a frame inherits its neighbour's signals undiluted and therefore satisfies the screen's criteria better than a genuine small gene. We present a multi-layer audit that tests this failure mode across genome annotation, transposon mutagenesis, CRISPR interference, homology, transcript mapping, proteomics, and population variation. We apply it to Rv2438A, a 92-codon conserved hypothetical open reading frame of Mycobacterium tuberculosis ranked first by our own dark-gene target screen. Rv2438A is superimposed on the essential NAD synthetase locus nadE: 44% lies within its coding sequence on the opposite strand, and the remainder covers its promoter and transcription start site. Consequently, three of five Himar1 sites lie within nadE, no CRISPRi guide can target Rv2438A without binding nadE, and the cross-species hit maps to the same nadE start junction. Rv2438A lacks its own transcription start site and is absent from every proteomic dataset that detects nadE. A genome-wide scan identifies six short, overlapping, uncharacterised loci among 3907 annotated genes, but only Rv2438A combines overlap and essentiality with non-detection across all proteomic datasets; rare genome-wide, it ranked first among screen hits. We provide an implementable audit workflow and a codon-position control, but measure the control's sensitivity as only two of five genes with attested protein, limiting it to confirmatory use. Overlap coordinates and neighbour-specific experimental resolution should therefore be reported before bacterial dark genes are prioritised.

CRISPR interference↗
PubMed2004

Estimation of the number of authentic orphan genes in bacterial genomes.

Genome annotation produces a considerable number of putative proteins lacking sequence similarity to known proteins. These are referred to as "orphans." The proportion of orphan genes varies among genomes, and is independent of genome size. In the present study, we show that the proportion of orphan genes roughly correlates with the isolation index of organisms (IIO), an indicator introduced in the present study, which represents the degree of isolation of a given genome as measured by sequence similarity. However, there are outlier genomes with respect to the linear correlation, consisting of those genomes that may contain excess amounts of orphan genes. Comparisons of genome sequences among closely related strains revealed that some of the annotated genes are not conserved, suggesting that they are ORFs occurring by chance. Exclusion of these non-conserved ORFs within closely related genomes improved the correlation between the proportion of orphan genes and the IIO values. Assuming that the correlation holds in general, this relationship was used to estimate the number of "authentic" orphan genes in a genome. Using this definition of authentic orphan genes, the anomalies arising from over-assignments, e.g., the percentages of structural annotations, were corrected for 16 genomes, including those of five archaea.

Amino Acid Sequence↗
PubMed2025

The chromosome-level genome assembly of Prunus cerasifera 'Atropurpurea'.

Prunus cerasifera 'Atropurpurea' (Purpleleaf Plum), known for its unique purple-red foliage, is an important ornamental plant that enhances the aesthetic value of urban greening. To explore the molecular mechanisms underlying leaf color changes, this study assembled the Purpleleaf Plum genome, providing new insights for related research. We used HiFi sequencing data to assemble its genome. After chromosome anchoring, the final genome size was 244.89&#x2009;Mb, with a contig N50 of 26.60&#x2009;Mb, and approximately 97.10% of sequences were anchored to 8 chromosomes. Genome annotation identified 28,231 protein-coding genes, with LTR transposons comprising 27.93% of the genome. BUSCO assessment revealed a genome completeness of 98.9%. Telomeric repeat analysis identified 14 telomeres, with six chromosomes capped by double telomeres and two chromosomes containing a single telomere. This high-quality Purpleleaf Plum genome provides a solid foundation for future gene function analysis, cultivar improvement, and genetic research, offering valuable resources for related fields.

Genome, Plant↗
PubMed2006

The GermOnline cross-species systems browser provides comprehensive information on genes and gene products relevant for sexual reproduction.

We report a novel release of the GermOnline knowledgebase covering genes relevant for the cell cycle, gametogenesis and fertility. GermOnline was extended into a cross-species systems browser including information on DNA sequence annotation, gene expression and the function of gene products. The database covers eight model organisms and Homo sapiens, for which complete genome annotation data are available. The database is now built around a sophisticated genome browser (Ensembl), our own microarray information management and annotation system (MIMAS) used to extensively describe experimental data obtained with high-density oligonucleotide microarrays (GeneChips) and a comprehensive system for online editing of database entries (MediaWiki). The RNA data include results from classical microarrays as well as tiling arrays that yield information on RNA expression levels, transcript start sites and lengths as well as exon composition. Members of the research community are solicited to help GermOnline curators keep database entries on genes and gene products complete and accurate. The database is accessible at http://www.germonline.org/.

Animals↗
PubMed2005

Gene finding in the chicken genome.

BACKGROUND: Despite the continuous production of genome sequence for a number of organisms, reliable, comprehensive, and cost effective gene prediction remains problematic. This is particularly true for genomes for which there is not a large collection of known gene sequences, such as the recently published chicken genome. We used the chicken sequence to test comparative and homology-based gene-finding methods followed by experimental validation as an effective genome annotation method. RESULTS: We performed experimental evaluation by RT-PCR of three different computational gene finders, Ensembl, SGP2 and TWINSCAN, applied to the chicken genome. A Venn diagram was computed and each component of it was evaluated. The results showed that de novo comparative methods can identify up to about 700 chicken genes with no previous evidence of expression, and can correctly extend about 40% of homology-based predictions at the 5' end. CONCLUSIONS: De novo comparative gene prediction followed by experimental verification is effective at enhancing the annotation of the newly sequenced genomes provided by standard homology-based methods.

Animals↗
PubMed2003

PseudoCyc, a pathway-genome database for Pseudomonas aeruginosa.

A pathway-genome database (PGDB) describes the entire genome of an organism, as well as its biochemical pathways, reactions, and enzymes. Our PathoLogic software can generate a PGDB from an annotated genome of an organism, predicting the metabolic reactions and pathways corresponding to the enzymes present in the annotation. We have used PathoLogic to generate a PGDB for PSEUDOMONAS AERUGINOSA, strain PAO1, called 'PseudoCyc', which includes 139 predicted pathways and 800 predicted reactions involving 623 chemical species and 718 enzymes. Analysis of the PathoLogic predictions of arginine metabolism and the beta-ketoadipate pathway, which are landmark pathways in P. AERUGINOSA, showed that they were for the most part correctly predicted. These studies also provided possible locations for two genes involved in the beta-ketoadipate pathway, PCAI and PCAJ, which are missing from the PAO1 annotation. PseudoCyc adds an extended dimension to the genome of P. AERUGINOSA, providing researchers with a helpful tool for the analysis of the genomic, proteomic, and metabolic information of the organism. The finding of the probable location of the PCAI and PCAJ genes is but one example of the discoveries facilitated by such a PGDB. PseudoCyc, along with PGDBs for 12 other organisms, is available at http://BioCyc.org/.

Adipates↗
PubMed2005

Expression profiling of the Arabidopsis ferric chelate reductase (FRO) gene family reveals differential regulation by iron and copper.

The Arabidopsis FRO2 gene encodes the iron deficiency-inducible ferric chelate reductase responsible for reduction of iron at the root surface; subsequent transport of iron across the plasma membrane is carried out by a ferrous iron transporter (IRT1). Genome annotation has identified seven additional FRO family members in the Arabidopsis genome. We used real-time RT-PCR to examine the expression of each FRO gene in different tissues and in response to iron and copper limitation. FRO2 and FRO5 are primarily expressed in roots while FRO8 is primarily expressed in shoots. FRO6 and FRO7 show high expression in all the green parts of the plant. FRO3 is expressed at high levels in roots and shoots, and expression of FRO3 is elevated in roots and shoots of iron-deficient plants. Interestingly, when plants are Cu-limited, the expression of FRO6 in shoot tissues is reduced. Expression of FRO3 is induced in roots and shoots by Cu-limitation. While it is known that FRO2 is expressed at high levels in the outer layers of iron-deficient roots, histochemical staining of FRO3-GUS plants revealed that FRO3 is predominantly expressed in the vascular cylinder of roots. Together our results suggest that FRO family members function in metal ion homeostasis in a variety of locations in the plant.

Arabidopsis↗
PubMed2005

Hemiascomycetous yeasts at the forefront of comparative genomics.

With more than a dozen species fully sequenced, as many as this partially sequenced, and more in development, yeasts are now used to explore the frontlines of comparative genomics of eukaryotes. Innovative procedures have been developed to compare and annotate genomes at various evolutionary distances, to identify short cis-acting regulatory elements, to map duplications, or to align syntenic blocks. Human and plant pathogens, in addition to yeasts that show a variety of interesting physiological properties, are included in this multidimensional comparative survey, which encompasses a very broad evolutionary range. As major steps of the evolutionary history of hemiascomycetous genomes emerge, precise questions on the general mechanisms of their evolution can be addressed, using both experimental and in silico methods.

Adaptation, Physiological↗
PubMed2003

Expressed sequence tags: alternative or complement to whole genome sequences?

Over three million sequences from approximately 200 plant species have been deposited in the publicly available plant expressed sequence tag (EST) sequence databases. Many of the ESTs have been sequenced as an alternative to complete genome sequencing or as a substrate for cDNA array-based expression analyses. This creates a formidable resource from both biodiversity and gene-discovery standpoints. Bioinformatics-based sequence analysis tools have extended the scope of EST analysis into the fields of proteomics, marker development and genome annotation. Although EST collections are certainly no substitute for a whole genome scaffold, this "poor man's genome" resource forms the core foundations for various genome-scale experiments within the as yet unsequenceable plant genomes.

Computational Biology↗
PubMed2003

IslandPath: aiding detection of genomic islands in prokaryotes.

UNLABELLED: Genomic islands (clusters of genes of potential horizontal origin in a prokaryotic genome) are frequently associated with a particular adaptation of a microbe that is of medical, agricultural or environmental importance, such as antibiotic resistance, pathogen virulence, or metal resistance. While many sequence features associated with such islands have been adopted separately in applications for analysis of genomic islands, including pathogenicity islands, there is no single application that integrates multiple features for island detection. IslandPath is a network service which incorporates multiple DNA signals and genome annotation features into a graphical display of a bacterial or archaeal genome, to aid the detection of genomic islands. AVAILABILITY: This application is available at http://www.pathogenomics.sfu.ca/islandpath and the source code is freely available, under GNU public licence, from the authors. SUPPLEMENTARY INFORMATION: An online help file, which includes analyses of the utility of IslandPath, can be found at http://www.pathogenomics.sfu.ca/islandpath/current/islandhelp.html

Archaea↗
PubMed2002

A comparative genomic method for computational identification of prokaryotic translation initiation sites.

The ever growing number of completely sequenced prokaryotic genomes facilitates cross-species comparisons by genomic annotation algorithms. This paper introduces a new probabilistic framework for comparative genomic analysis and demonstrates its utility in the context of improving the accuracy of prokaryotic gene start site detection. Our frame work employs a product hidden Markov model (PROD-HMM) with state architecture to model the species-specific trinucleotide frequency patterns in sequences immediately upstream and downstream of a translation start site and to detect the contrasting non-synonymous (amino acid changing) and synonymous (silent) substitution rates that differentiate prokaryotic coding from intergenic regions. Depending on the intricacy of the features modeled by the hidden state architecture, intergenic, regulatory, promoter and coding regions can be delimited by this method. The new system is evaluated using a preliminary set of orthologous Pyrococcus gene pairs, for which it demonstrates an improved accuracy of detection. Its robustness is confirmed by analysis with cross-validation of an experimentally verified set of Escherichia coli K-12 and Salmonella thyphimurium LT2 orthologs. The novel architecture has a number of attractive features that distinguish it from previous comparative models such as pair-HMMs.

Algorithms↗