Enhancing Bioinformatics and Genomics Courses: Building Capacity and Skills via Lab Meeting Activities: Fostering a Culture of Critical Capacities to Read, Write, Communicate and Engage in Rigorous Scientific Exchanges.

Reading, writing, publishing, and publicly presenting scientific works are vital for a young researcher's profile building and career development. Generally, the traditional educational curricula do not offer training possibilities to learn and practice how to prepare, write, and present scientific works. These are rather a part of lab meeting activities in research groups.

Designing and running an advanced Bioinformatics and genome analyses course in Tunisia.

Genome data, with underlying new knowledge, are accumulating at exponential rate thanks to ever-improving sequencing technologies and the parallel development of dedicated efficient Bioinformatics methods and tools. Advanced Education in Bioinformatics and Genome Analyses is to a large extent not accessible to students in developing countries where endeavors to set up Bioinformatics courses concern most often only basic levels. Here, we report a pioneering pilot experience concerning the design and implementation, from scratch, of a three-months advanced and extensive course in Bioinformatics and Genome Analyses in the Institut Pasteur de Tunis.

Genome Data Exploration Using Correspondence Analysis.

Recent developments of sequencing technologies that allow the production of massive amounts of genomic and genotyping data have highlighted the need for synthetic data representation and pattern recognition methods that can mine and help discovering biologically meaningful knowledge included in such large data sets. Correspondence analysis (CA) is an exploratory descriptive method designed to analyze two-way data tables, including some measure of association between rows and columns. It constructs linear combinations of variables, known as factors.

Inferring Orthologs: Open Questions and Perspectives.

With the increasing number of sequenced genomes and their comparisons, the detection of orthologs is crucial for reliable functional annotation and evolutionary analyses of genes and species. Yet, the dynamic remodeling of genome content through gain, loss, transfer of genes, and segmental and whole-genome duplication hinders reliable orthology detection. Moreover, the lack of direct functional evidence and the questionable quality of some available genome sequences and annotations present additional difficulties to assess orthology.

Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features among budding yeasts (Saccharomycotina).

The numerous yeast genome sequences presently available provide a rich source of information for functional as well as evolutionary genomics but unequally cover the large phylogenetic diversity of extant yeasts. We present here the complete sequence of the nuclear genome of the haploid-type strain of Kuraishia capsulata (CBS1993(T)), a nitrate-assimilating Saccharomycetales of uncertain taxonomy, isolated from tunnels of insect larvae underneath coniferous barks and characterized by its copious production of extracellular polysaccharides. The sequence is composed of seven scaffolds, one per chromosome, totaling 11.

Detection and characterization of megasatellites in orthologous and nonorthologous genes of 21 fungal genomes.

Megasatellites are large DNA tandem repeats, originally described in Candida glabrata, in protein-coding genes. Most of the genes in which megasatellites are found are of unknown function. In this work, we extended the search for megasatellites to 20 additional completely sequenced fungal genomes and extracted 216 megasatellites in 203 out of 142,121 genes, corresponding to the most exhaustive description of such genetic elements available today.

Investigation of secreted protein transcripts as early biomarkers for type 1 diabetes in the mouse model.

Type 1 diabetes (T1D) represents a serious health burden in the world, complicated by the fact that disease onset can be preceded by a long time period without evident clinical signs. It would be then of critical importance to detect the disease in its early stages. In this direction, we seek here to identify early preinflammatory markers for autoimmune diabetes, mining our previously reported transcriptome data relevant to distinct early sub-phenotypes in the NOD mouse, associated with early insulin autoantibodies (E-IAA).

SuperPartitions: detection and classification of orthologs.

The proper detection of orthologs is crucial for evolutionary studies of genes and species. Despite large efforts to solve this problem the methodological situation appears unsettled to a large extent and the "quest for orthologs" is still an ongoing task in large-scale genome comparisons. Here, we introduce a simple operational framework for the detection of orthologs and their classification.

Use of fine-needle aspiration for diagnosis of Mycobacterium ulcerans infection.

Noninvasive methods for the bacteriological diagnosis of early-stage Mycobacterium ulcerans infection are not available. It was recently shown that fine-needle aspiration (FNA) could be used for diagnosing M. ulcerans infection in ulcerative lesions.

Promiscuous DNA in the nuclear genomes of hemiascomycetous yeasts.

Abstract Transfer of fragments of mtDNA to the nuclear genome is a general phenomenon that gives rise to NUMTs (NUclear sequences of MiTochondrial origin). We present here the first comparative analysis of the NUMT content of entirely sequenced species belonging to a monophyletic group, the hemiascomycetous yeasts (Candida glabrata, Kluyveromyces lactis, Kluyveromyces thermotolerans, Debaryomyces hansenii and Yarrowia lipolytica, along with the updated NUMT content of Saccharomyces cerevisiae). This study revealed a huge diversity in NUMT number and organization across the six species.

Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva.

Background: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment.

Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer.

Mycobacterium ulcerans is found in aquatic ecosystems and causes Buruli ulcer in humans, a neglected but devastating necrotic disease of subcutaneous tissue that is rampant throughout West and Central Africa. Here, we report the complete 5.8-Mb genome sequence of M.

Evolution of proteomes: fundamental signatures and global trends in amino acid compositions.

Background: The evolutionary characterization of species and lifestyles at global levels is nowadays a subject of considerable interest, particularly with the availability of many complete genomes. Are there specific properties associated with lifestyles and phylogenies? What are the underlying evolutionary trends? One of the simplest analyses to address such questions concerns characterization of proteomes at the amino acids composition level.

Results: In this work, amino acid compositions of a large set of 208 proteomes, with significant number of representatives from the three phylogenetic domains and different lifestyles are analyzed, resorting to an appropriate multidimensional method: Correspondence analysis.

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus.

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A.

Genome trees from conservation profiles.

The concept of the genome tree depends on the potential evolutionary significance in the clustering of species according to similarities in the gene content of their genomes. In this respect, genome trees have often been identified with species trees. With the rapid expansion of genome sequence data it becomes of increasing importance to develop accurate methods for grasping global trends for the phylogenetic signals that mutually link the various genomes.

A human-curated annotation of the Candida albicans genome.

Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy.

Aspergillus fumigatus: saprophyte or pathogen?

Large-scale genome comparisons have shown that no gene sets are shared exclusively by both Aspergillus fumigatus and any other human pathogen sequenced to date, such as Candida or Cryptococcus species. By contrast, and in agreement with the environmental occurrence of this fungus in decaying vegetation, the enzymatic machinery required by a fungus to colonize plant substrates has been found in the A. fumigatus genome.

Continued colonization of the human genome by mitochondrial DNA.

Integration of mitochondrial DNA fragments into nuclear chromosomes (giving rise to nuclear DNA sequences of mitochondrial origin, or NUMTs) is an ongoing process that shapes nuclear genomes. In yeast this process depends on double-strand-break repair. Since NUMTs lack amplification and specific integration mechanisms, they represent the prototype of exogenous insertions in the nucleus.

Genome evolution in yeasts.

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates.

Novel transporters from hemiascomycete yeasts.

We screened nearly one thousand random sequenced targets obtained by partial sequencing of 13 hemiascomycete genomes identified by higher amino acid sequence similarity to a non-Saccharomyces cerevisiae protein than to a S. Cerevisiae protein. Among those sequences we have identified 36 novel phylogenetic clusters of putative transporters which, according to the Transport Commission system (TC-DB, 2002; http:// tcdb.

A novel design of whole-genome microarray probes for Saccharomyces cerevisiae which minimizes cross-hybridization.

Background: Numerous DNA microarray hybridization experiments have been performed in yeast over the last years using either synthetic oligonucleotides or PCR-amplified coding sequences as probes. The design and quality of the microarray probes are of critical importance for hybridization experiments as well as subsequent analysis of the data.

Results: We present here a novel design of Saccharomyces cerevisiae microarrays based on a refined annotation of the genome and with the aim of reducing cross-hybridization between related sequences.

Expressed sequence tag analysis of the human pathogen Paracoccidioides brasiliensis yeast phase: identification of putative homologues of Candida albicans virulence and pathogenicity genes.

Paracoccidioides brasiliensis, a thermodimorphic fungus, is the causative agent of the prevalent systemic mycosis in Latin America, paracoccidioidomycosis. We present here a survey of expressed genes in the yeast pathogenic phase of P. brasiliensis.

Amino acid composition of genomes, lifestyles of organisms, and evolutionary trends: a global picture with correspondence analysis.

Can we infer the lifestyle of an organism from the characteristic properties of its genome? More precisely, what are the relations between easily quantifiable properties from genomic sequences, such as amino-acid compositions, and more subtle characteristics concerning for example lifestyles or evolutionary trends? Here, we seek a global picture for such properties, based on a large number (56) of complete genomes, including significant numbers of representatives from the three domains of life. We consider the amino acid compositions of the predicted proteomes, and we use correspondence analysis, as a multivariate method to extract the relevant information from the large-scale data. From these analyses we derive a series of conclusions, concerning lifestyles, as well as physico-chemical and evolutionary trends: (1) correspondence analysis of the amino acid compositions permits discrimination between the three known lifestyles (mesophily/thermophily/hyperthermophily).

Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22.

A 3,673-bp murine cDNA predicted to encode a glycosylphosphatidylinositol-anchored protein of 1,088 amino acids was isolated during a study aimed at identifying transcripts specifically expressed in the inner ear. This inner ear-specific protein, otoancorin, shares weak homology with megakaryocyte potentiating factor/mesothelin precursor. Otoancorin is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels.