DeCAF—Discrimination, Comparison, Alignment Tool for 2D PHarmacophores

Comparison of small molecules is a common component of many cheminformatics workflows, including the design of new compounds and libraries as well as side-effect predictions and drug repurposing. Currently, large-scale comparison methods rely mostly on simple fingerprint representation of molecules, which take into account the structural similarities of compounds. Methods that utilize 3D information depend on multiple conformer generation steps, which are computationally expensive and can greatly influence their results. The aim of this study was to augment molecule representation with spatial and physicochemical properties while simultaneously avoiding conformer generation. To achieve this goal, we describe a molecule as an undirected graph in which the nodes correspond to atoms with pharmacophoric properties and the edges of the graph represent the distances between features. This approach combines the benefits of a conformation-free representation of a molecule with additional spatial information. We implemented our approach as an open-source Python module called DeCAF (Discrimination, Comparison, Alignment tool for 2D PHarmacophores), freely available at http://bitbucket.org/marta-sd/decaf. We show DeCAF’s strengths and weaknesses with usage examples and thorough statistical evaluation. Additionally, we show that our method can be manually tweaked to further improve the results for specific tasks. The full dataset on which DeCAF was evaluated and all scripts used to calculate and analyze the results are also provided

Cut-and-paste transposons in fungi with diverse lifestyles

Transposons (TEs) shape genomes via recombination and transposition, lead to chromosomal rearrangements, create new gene neighbourhoods and alter gene expression. They play key roles in adaptation either to symbiosis in Amanita genus or to pathogenicity in Pyrenophora tritici-repentis. Despite growing evidence of their importance, the abundance and distribution of mobile elements replicating in a “cut and paste” fashion is barely described so far. In order to improve our knowledge on this old and ubiquitous class of transposable elements, 1,730 fungal genomes were scanned using both de novo and homology-based approaches. DNA TEs have been identified across the whole dataset and display uneven distribution from both DNA TE classification and fungal taxonomy perspectives. DNA TE content correlates with genome size, which confirms that many transposon families proliferate simultaneously. In contrast, it is independent from intron density, average gene distance and GC content. TE count is associated with species’ lifestyle and tends to be elevated in plant symbionts and decreased in animal parasites. Lastly, we found that fungi with both RIP and RNAi systems have more total DNA TE sequences but less elements retaining a functional transposase, what reflects stringent control over transposition

The online student as a driving force in the transformation of the Polish Virtual University

La Universitat Virtual Polonesa (PUW) ha sofert una transició dramàtica perquè s'ha esforçat per desenvolupar un programa d'estudis important i viable; ha passat d'aplicar una fórmula d'una universitat tradicional adaptada per a l'aprenentatge i la docència en línia a ser una institució d'ensenyament superior moderna, plenament integrada, centrada en els estudiants i que funciona en l'entorn de l'aprenentatge virtual. La idea diferenciadora dels estudiants com a clients i destinataris de l'oferta universitària virtual s'ha anat perfilant durant la transició de la PUW, i la pràctica de les tutories en línia ha millorat considerablement. S'ha desenvolupat el sistema de suport de l'estudiant i del consultor i ha esdevingut una part essencial del sistema de la PUW. Aquest article proporciona una visió general de les accions que s'han endegat a la PUW, les quals han ajudat a crear una atmosfera d'aprenentatge il·limitat i han ajudat els estudiants en la seva recerca d'ampliació del coneixement i millora de les habilitats pràctiques. També parla de la importància de tenir en compte l'abast sencer dels compromisos parcials que han d'afrontar els estudiants en línia

The online student as a driving force in the transformation of the Polish Virtual University

La Universitat Virtual Polonesa (PUW) ha sofert una transició dramàtica perquè s'ha esforçat per desenvolupar un programa d'estudis important i viable; ha passat d'aplicar una fórmula d'una universitat tradicional adaptada per a l'aprenentatge i la docència en línia a ser una institució d'ensenyament superior moderna, plenament integrada, centrada en els estudiants i que funciona en l'entorn de l'aprenentatge virtual. La idea diferenciadora dels estudiants com a clients i destinataris de l'oferta universitària virtual s'ha anat perfilant durant la transició de la PUW, i la pràctica de les tutories en línia ha millorat considerablement. S'ha desenvolupat el sistema de suport de l'estudiant i del consultor i ha esdevingut una part essencial del sistema de la PUW. Aquest article proporciona una visió general de les accions que s'han endegat a la PUW, les quals han ajudat a crear una atmosfera d'aprenentatge il·limitat i han ajudat els estudiants en la seva recerca d'ampliació del coneixement i millora de les habilitats pràctiques. També parla de la importància de tenir en compte l'abast sencer dels compromisos parcials que han d'afrontar els estudiants en línia

Fungal lifestyle reflected in serine protease repertoire

Fungi are able to switch between different lifestyles in order to adapt to environmental changes. Their ecological strategy is connected to their secretome as fungi obtain nutrients by secreting hydrolytic enzymes to their surrounding and acquiring the digested molecules. We focus on fungal serine proteases (SPs), the phylogenetic distribution of which is barely described so far. In order to collect a complete set of fungal proteases, we searched over 600 fungal proteomes. Obtained results suggest that serine proteases are more ubiquitous than expected. From 54 SP families described in MEROPS Peptidase Database, 21 are present in fungi. Interestingly, 14 of them are also present in Metazoa and Viridiplantae – this suggests that, except one (S64), all fungal SP families evolved before plants and fungi diverged. Most representatives of sequenced eukaryotic lineages encode a set of 13–16 SP families. The number of SPs from each family varies among the analysed taxa. The most abundant are S8 proteases. In order to verify hypotheses linking lifestyle and expansions of particular SP, we performed statistical analyses and revealed previously undescribed associations. Here, we present a comprehensive evolutionary history of fungal SP families in the context of fungal ecology and fungal tree of life

Transposable elements contribute to fungal genes and impact fungal lifestyle

Abstract The last decade brought a still growing experimental evidence of mobilome impact on host’s gene expression. We systematically analysed genomic location of transposable elements (TEs) in 625 publicly available fungal genomes from the NCBI database in order to explore their potential roles in genome evolution and correlation with species’ lifestyle. We found that non-autonomous TEs and remnant copies are evenly distributed across genomes. In consequence, they also massively overlap with regions annotated as genes, which suggests a great contribution of TE-derived sequences to host’s coding genome. Younger and potentially active TEs cluster with one another away from genic regions. This non-randomness is a sign of either selection against insertion of TEs in gene proximity or target site preference among some types of TEs. Proteins encoded by genes with old transposable elements insertions have significantly less repeat and protein-protein interaction motifs but are richer in enzymatic domains. However, genes only proximal to TEs do not display any functional enrichment. Our findings show that adaptive cases of TE insertion remain a marginal phenomenon, and the overwhelming majority of TEs are evolving neutrally. Eventually, animal-related and pathogenic fungi have more TEs inserted into genes than fungi with other lifestyles. This is the first systematic, kingdom-wide study concerning mobile elements and their genomic neighbourhood. The obtained results should inspire further research concerning the roles TEs played in evolution and how they shape the life we know today

Development of a Protein-Ligand Extended Connectivity (PLEC) Fingerprint and Its Application for Binding Affinity Predictions.

Fingerprints (FPs) are the most common small molecule representation in cheminformatics. There are a wide variety of fingerprints, and the Extended Connectivity Fingerprint (ECFP) is one of the best-suited for general applications. Despite the overall FP abundance, only a few FPs represent the 3D structure of the molecule, and hardly any encode protein-ligand interactions. Here, we present a Protein-Ligand Extended Connectivity (PLEC) fingerprint that implicitly encodes protein-ligand interactions by pairing the ECFP environments from the ligand and the protein. PLEC fingerprints were used to construct different machine learning (ML) models tailored for predicting protein-ligand affinities (pKi/d). Even the simplest linear model built on the PLEC fingerprint achieved Rp=0.83 on the PDBbind v2016 "core set”, demonstrating its descriptive power. The PLEC fingerprint has been implemented in the Open Drug Discovery Toolkit (https://github.com/oddt/oddt).</div