Sequanix: a dynamic graphical interface for Snakemake workflows.

Summary: We designed a PyQt graphical user interface-Sequanix-aimed at democratizing the use of Snakemake pipelines in the NGS space and beyond. By default, Sequanix includes Sequana NGS pipelines (Snakemake format) (http://sequana.readthedocs.io), and is also capable of loading any external Snakemake pipeline. New users can easily, visually, edit configuration files of expert-validated pipelines and can interactively execute these production-ready workflows. Sequanix will be useful to both Snakemake developers in exposing their pipelines and to a wide audience of users. Availability and implementation: Source on http://github.com/sequana/sequana, bio-containers on http://bioconda.github.io and Singularity hub (http://singularity-hub.org). Contact: dimitri.desvillechabrol@pasteur.fr or thomas.cokelaer@pasteur.fr. Supplementary information: Supplementary data are available at Bioinformatics online.

AMMOS2: a web server for protein-ligand-water complexes refinement via molecular mechanics.

AMMOS2 is an interactive web server for efficient computational refinement of protein-small organic molecule complexes. The AMMOS2 protocol employs atomic-level energy minimization of a large number of experimental or modeled protein-ligand complexes. The web server is based on the previously developed standalone software AMMOS (Automatic Molecular Mechanics Optimization for in silico Screening). AMMOS utilizes the physics-based force field AMMP sp4 and performs optimization of protein-ligand interactions at five levels of flexibility of the protein receptor. The new version 2 of AMMOS implemented in the AMMOS2 web server allows the users to include explicit water molecules and individual metal ions in the protein-ligand complexes during minimization. The web server provides comprehensive analysis of computed energies and interactive visualization of refined protein-ligand complexes. The ligands are ranked by the minimized binding energies allowing the users to perform additional analysis for drug discovery or chemical biology projects. The web server has been extensively tested on 21 diverse protein-ligand complexes. AMMOS2 minimization shows consistent improvement over the initial complex structures in terms of minimized protein-ligand binding energies and water positions optimization. The AMMOS2 web server is freely available without any registration requirement at the URL: http://drugmod.rpbs.univ-paris-diderot.fr/ammosHome.php.

Deciphering the Role of PIG1 and DHN-Melanin in Scedosporium apiospermum Conidia.

Scedosporium apiospermum is a saprophytic filamentous fungus involved in human infections, of which the virulence factors that contribute to pathogenesis are still poorly characterized. In particular, little is known about the specific role of dihydroxynaphtalene (DHN)-melanin, located on the external layer of the conidia cell wall. We previously identified a transcription factor, PIG1, which may be involved in DHN-melanin biosynthesis. To elucidate the role of PIG1 and DHN-melanin in S. apiospermum, a CRISPR-Cas9-mediated PIG1 deletion was carried out from two parental strains to evaluate its impact on melanin biosynthesis, conidia cell-wall assembly, and resistance to stress, including the ability to survive macrophage engulfment. ΔPIG1 mutants did not produce melanin and showed a disorganized and thinner cell wall, resulting in a lower survival rate when exposed to oxidizing conditions, or high temperature. The absence of melanin increased the exposure of antigenic patterns on the conidia surface. PIG1 regulates the melanization of S. apiospermum conidia, and is involved in the survival to environmental injuries and to the host immune response, that might participate in virulence. Moreover, a transcriptomic analysis was performed to explain the observed aberrant septate conidia morphology and found differentially expressed genes, underlining the pleiotropic function of PIG1.

BioConvert: a comprehensive format converter for life sciences.

Bioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To overcome these difficulties, we initiated BioConvert, a collaborative project to facilitate the conversion of life science data from one format to another. BioConvert aggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently, BioConvert supports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users, BioConvert can also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface to BioConvert, hence allowing direct use for the community.

Dynamics of extended-spectrum beta-lactamase-producing Enterobacterales colonization in long-term carriers following travel abroad.

Travel to tropical regions is associated with high risk of acquiring extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) that are typically cleared in less than 3 months following return. The conditions leading to persistent carriage that exceeds 3 months in some travellers require investigation. Whole-genome sequencing (Illumina MiSeq) was performed on the 82 ESBL-E isolates detected upon return and 1, 2, 3, 6 and 12 months later from the stools of 11 long-term (>3 months) ESBL-E carriers following travel abroad. One to five different ESBL Escherichia coli strains were detected per traveller upon return, and this diminished to one after 3 months. Long-term carriage was due to the presence of the same ESBL E. coli strain, for more than 3 months, in 9 out of 11 travellers, belonging to epidemic sequence type complexes (STc 10, 14, 38, 69, 131 and 648). The mean carriage duration of strains belonging to phylogroups B2/D/F, associated with extra-intestinal virulence, was higher than that for commensal-associated A/B1/E phylogroups (3.5 vs 0.5 months, P=0.021). Genes encoding iron capture systems (fyuA, irp), toxins (senB, sat), adhesins (flu, daaF, afa/nfaE, pap, ecpA) and colicin (cjrA) were more often present in persistent strains than in transient ones. Single-nucleotide polymorphism (SNP) analysis in persistent strains showed a maximum divergence of eight SNPs over 12 months without signs of adaptation. Genomic plasticity was observed during the follow-up with the loss or gain of mobile genetic elements such as plasmids, integrons and/or transposons that may contain resistance genes at different points in the follow-up. Long-term colonization of ESBL-E following travel is primarily due to the acquisition of E. coli strains belonging to epidemic clones and harbouring 'virulence genes', allowing good adaptation to the intestinal microbiota.

Sequana coverage: detection and characterization of genomic variations using running median and mixture models.

Background: In addition to mapping quality information, the Genome coverage contains valuable biological information such as the presence of repetitive regions, deleted genes, or copy number variations (CNVs). It is essential to take into consideration atypical regions, trends (e.g., origin of replication), or known and unknown biases that influence coverage. It is also important that reported events have robust statistics (e.g. z-score) associated with their detections as well as precise location. Results: We provide a stand-alone application, sequana_coverage, that reports genomic regions of interest (ROIs) that are significantly over- or underrepresented in high-throughput sequencing data. Significance is associated with the events as well as characteristics such as length of the regions. The algorithm first detrends the data using an efficient running median algorithm. It then estimates the distribution of the normalized genome coverage with a Gaussian mixture model. Finally, a z-score statistic is assigned to each base position and used to separate the central distribution from the ROIs (i.e., under- and overcovered regions). A double thresholds mechanism is used to cluster the genomic ROIs. HTML reports provide a summary with interactive visual representations of the genomic ROIs with standard plots and metrics. Genomic variations such as single-nucleotide variants or CNVs can be effectively identified at the same time.