GeneViTo: Visualizing gene-product functional and structural features in genomic datasets

Background  

The availability of increasing amounts of sequence data from completely sequenced genomes boosts the development of new computational methods for automated genome annotation and comparative genomics. Therefore, there is a need for tools that facilitate the visualization of raw data and results produced by bioinformatics analysis, providing new means for interactive genome exploration. Visual inspection can be used as a basis to assess the quality of various analysis algorithms and to aid in-depth genomic studies.     

Nonsynonymous substitution rate (Ka) is a relatively consistent parameter for defining fast-evolving and slow-evolving protein-coding genes

Background  

Mammalian genome sequence data are being acquired in large quantities and at enormous speeds. We now have a tremendous opportunity to better understand which genes are the most variable or conserved, and what their particular functions and evolutionary dynamics are, through comparative genomics.     

u-Genome: a database on genome design in unicellular genomes

Unicellular eukaryotes were among the first ones to be selected for complete genome sequencing because of the small size of their genomes and their interactions with humans and a broad range of animals and plants. Currently, ten completely sequenced unicellular genome sequences have been publicly released and as the number of available unicellular genomes increases, comparative genomics analysis within this group of organisms becomes more and more instructive. However, such an analysis is difficult to carry out without a suitable platform gathering not only the original annotations but also relevant information available in public databases or obtained by applying common bioinformatics methods. With the aim of solving these difficulties, we have developed a web-accessible database named u-Genome, the unicellular genome design database. The database is unique in featuring three datasets namely (1) orthologous proteins (2) paralogous proteins and (3) statistical distributions on exons, introns, intergenic DNA and correlations between them. A tool, Uniview, designed to visualize the gene structures for individual genes in the genome is also integrated. This database is of importance in understanding unicellular genome design and architecture and evolution related studies. The database is available through a web interface at http://sege.ntu.edu.sg/wester/ugenome.     

Comparative assessment of performance and genome dependence among phylogenetic profiling methods

Background  

The rapidly increasing speed with which genome sequence data can be generated will be accompanied by an exponential increase in the number of sequenced eukaryotes. With the increasing number of sequenced eukaryotic genomes comes a need for bioinformatic techniques to aid in functional annotation. Ideally, genome context based techniques such as proximity, fusion, and phylogenetic profiling, which have been so successful in prokaryotes, could be utilized in eukaryotes. Here we explore the application of phylogenetic profiling, a method that exploits the evolutionary co-occurrence of genes in the assignment of functional linkages, to eukaryotic genomes.     

MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in Metazoa

Background  

Mitochondria are sub-cellular organelles that have a central role in energy production and in other metabolic pathways of all eukaryotic respiring cells. In the last few years, with more and more genomes being sequenced, a huge amount of data has been generated providing an unprecedented opportunity to use the comparative analysis approach in studies of evolution and functional genomics with the aim of shedding light on molecular mechanisms regulating mitochondrial biogenesis and metabolism.     

EDGAR: A software framework for the comparative analysis of prokaryotic genomes

Background  

The introduction of next generation sequencing approaches has caused a rapid increase in the number of completely sequenced genomes. As one result of this development, it is now feasible to analyze large groups of related genomes in a comparative approach. A main task in comparative genomics is the identification of orthologous genes in different genomes and the classification of genes as core genes or singletons.     

Improving the specificity of high-throughput ortholog prediction

Background  

Orthologs (genes that have diverged after a speciation event) tend to have similar function, and so their prediction has become an important component of comparative genomics and genome annotation. The gold standard phylogenetic analysis approach of comparing available organismal phylogeny to gene phylogeny is not easily automated for genome-wide analysis; therefore, ortholog prediction for large genome-scale datasets is typically performed using a reciprocal-best-BLAST-hits (RBH) approach. One problem with RBH is that it will incorrectly predict a paralog as an ortholog when incomplete genome sequences or gene loss is involved. In addition, there is an increasing interest in identifying orthologs most likely to have retained similar function.     

Genomic exploration of the hemiascomycetous yeasts: 1. A set of yeast species for molecular evolution studies

The identification of molecular evolutionary mechanisms in eukaryotes is approached by a comparative genomics study of a homogeneous group of species classified as Hemiascomycetes. This group includes Saccharomyces cerevisiae, the first eukaryotic genome entirely sequenced, back in 1996. A random sequencing analysis has been performed on 13 different species sharing a small genome size and a low frequency of introns. Detailed information is provided in the 20 following papers. Additional tables available on websites describe the ca. 20000 newly identified genes. This wealth of data, so far unique among eukaryotes, allowed us to examine the conservation of chromosome maps, to identify the 'yeast-specific' genes, and to review the distribution of gene families into functional classes. This project conducted by a network of seven French laboratories has been designated 'Génolevures'.     

Visualization of comparative genomic analyses by BLAST score ratio

Background  

The first microbial genome sequence, Haemophilus influenzae, was published in 1995. Since then, more than 400 microbial genome sequences have been completed or commenced. This massive influx of data provides the opportunity to obtain biological insights through comparative genomics. However few tools are available for this scale of comparative analysis.     

PhyloPro: a web-based tool for the generation and visualization of phylogenetic profiles across Eukarya

SUMMARY: With increasing numbers of eukaryotic genome sequences, phylogenetic profiles of eukaryotic genes are becoming increasingly informative. Here, we introduce a new web-tool Phylopro (http://compsysbio.org/phylopro/), which uses the 120 available eukaryotic genome sequences to visualize the evolutionary trajectories of user-defined subsets of model organism genes. Applied to pathways or complexes, PhyloPro allows the user to rapidly identify core conserved elements of biological processes together with those that may represent lineage-specific innovations. PhyloPro thus provides a valuable resource for the evolutionary and comparative studies of biological systems.     

A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis

Background  

To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available.     

Comparative genomics - a perspective

The rapidly emerging field of comparative genomics has yielded dramatic results. Comparative genome analysis has become feasible with the availability of a number of completely sequenced genomes. Comparison of complete genomes between organisms allow for global views on genome evolution and the availability of many completely sequenced genomes increases the predictive power in deciphering the hidden information in genome design, function and evolution. Thus, comparison of human genes with genes from other genomes in a genomic landscape could help assign novel functions for un-annotated genes. Here, we discuss the recently used techniques for comparative genomics and their derived inferences in genome biology.     

Evolutionary relationships of <Emphasis Type="Italic">Fusobacterium nucleatum</Emphasis> based on phylogenetic analysis and comparative genomics

Background  

The phylogenetic position and evolutionary relationships of Fusobacteria remain uncertain. Especially intriguing is their relatedness to low G+C Gram positive bacteria (Firmicutes) by ribosomal molecular phylogenies, but their possession of a typical gram negative outer membrane. Taking advantage of the recent completion of the Fusobacterium nucleatum genome sequence we have examined the evolutionary relationships of Fusobacterium genes by phylogenetic analysis and comparative genomics tools.     

The COG database: an updated version includes eukaryotes

Background

The availability of multiple, essentially complete genome sequences of prokaryotes and eukaryotes spurred both the demand and the opportunity for the construction of an evolutionary classification of genes from these genomes. Such a classification system based on orthologous relationships between genes appears to be a natural framework for comparative genomics and should facilitate both functional annotation of genomes and large-scale evolutionary studies.

Results

We describe here a major update of the previously developed system for delineation of Clusters of Orthologous Groups of proteins (COGs) from the sequenced genomes of prokaryotes and unicellular eukaryotes and the construction of clusters of predicted orthologs for 7 eukaryotic genomes, which we named KOGs after eukaryotic orthologous groups. The COG collection currently consists of 138,458 proteins, which form 4873 COGs and comprise 75% of the 185,505 (predicted) proteins encoded in 66 genomes of unicellular organisms. The eukaryotic orthologous groups (KOGs) include proteins from 7 eukaryotic genomes: three animals (the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and Homo sapiens), one plant, Arabidopsis thaliana, two fungi (Saccharomyces cerevisiae and Schizosaccharomyces pombe), and the intracellular microsporidian parasite Encephalitozoon cuniculi. The current KOG set consists of 4852 clusters of orthologs, which include 59,838 proteins, or ~54% of the analyzed eukaryotic 110,655 gene products. Compared to the coverage of the prokaryotic genomes with COGs, a considerably smaller fraction of eukaryotic genes could be included into the KOGs; addition of new eukaryotic genomes is expected to result in substantial increase in the coverage of eukaryotic genomes with KOGs. Examination of the phyletic patterns of KOGs reveals a conserved core represented in all analyzed species and consisting of ~20% of the KOG set. This conserved portion of the KOG set is much greater than the ubiquitous portion of the COG set (~1% of the COGs). In part, this difference is probably due to the small number of included eukaryotic genomes, but it could also reflect the relative compactness of eukaryotes as a clade and the greater evolutionary stability of eukaryotic genomes.

Conclusion

The updated collection of orthologous protein sets for prokaryotes and eukaryotes is expected to be a useful platform for functional annotation of newly sequenced genomes, including those of complex eukaryotes, and genome-wide evolutionary studies.     

Is mammalian chromosomal evolution driven by regions of genome fragility?

Background  

A fundamental question in comparative genomics concerns the identification of mechanisms that underpin chromosomal change. In an attempt to shed light on the dynamics of mammalian genome evolution, we analyzed the distribution of syntenic blocks, evolutionary breakpoint regions, and evolutionary breakpoints taken from public databases available for seven eutherian species (mouse, rat, cattle, dog, pig, cat, and horse) and the chicken, and examined these for correspondence with human fragile sites and tandem repeats.     

Assessing the evolutionary rate of positional orthologous genes in prokaryotes using synteny data

Background  

Comparison of completely sequenced microbial genomes has revealed how fluid these genomes are. Detecting synteny blocks requires reliable methods to determining the orthologs among the whole set of homologs detected by exhaustive comparisons between each pair of completely sequenced genomes. This is a complex and difficult problem in the field of comparative genomics but will help to better understand the way prokaryotic genomes are evolving.     

Assessment of the relationship between signal intensities and transcript concentration for Affymetrix GeneChip®arrays

Background

The availability of both mouse and human draft genomes has marked the beginning of a new era of comparative mammalian genomics. The two available mouse genome assemblies, from the public mouse genome sequencing consortium and Celera Genomics, were obtained using different clone libraries and different assembly methods.

Results

We present here a critical comparison of the two latest mouse genome assemblies. The utility of the combined genomes is further demonstrated by comparing them with the human 'golden path' and through a subsequent analysis of a resulting conserved sequence element (CSE) database, which allows us to identify over 6,000 potential novel genes and to derive independent estimates of the number of human protein-coding genes.

Conclusion

The Celera and public mouse assemblies differ in about 10% of the mouse genome. Each assembly has advantages over the other: Celera has higher accuracy in base-pairs and overall higher coverage of the genome; the public assembly, however, has higher sequence quality in some newly finished bacterial artifical chromosome clone (BAC) regions and the data are freely accessible. Perhaps most important, by combining both assemblies, we can get a better annotation of the human genome; in particular, we can obtain the most complete set of CSEs, one third of which are related to known genes and some others are related to other functional genomic regions. More than half the CSEs are of unknown function. From the CSEs, we estimate the total number of human protein-coding genes to be about 40,000. This searchable publicly available online CSEdb will expedite new discoveries through comparative genomics.