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Wass M.N.,Imperial College London | Wass M.N.,Structural Computational Biology Group | Barton G.,Imperial College London | Sternberg M.J.E.,Imperial College London
Nucleic Acids Research | Year: 2012

Only a small fraction of known proteins have been functionally characterized, making protein function prediction essential to propose annotations for uncharacterized proteins. In recent years many function prediction methods have been developed using various sources of biological data from protein sequence and structure to gene expression data. Here we present the CombFunc web server, which makes Gene Ontology (GO)-based protein function predictions. CombFunc incorporates ConFunc, our existing function prediction method, with other approaches for function prediction that use protein sequence, gene expression and protein-protein interaction data. In benchmarking on a set of 1686 proteins CombFunc obtains precision and recall of 0.71 and 0.64 respectively for gene ontology molecular function terms. For biological process GO terms precision of 0.74 and recall of 0.41 is obtained. CombFunc is available at http://www.sbg.bio.ic.ac.uk/combfunc. © 2012 The Author(s). Source

Guillou E.,DNA Replication Group | Guillou E.,Laboratoire Of Biologie Moleculaire Eucaryote | Ibarra A.,DNA Replication Group | Coulon V.,Montpellier University | And 8 more authors.
Genes and Development | Year: 2010

Genomic DNA is packed in chromatin fibers organized in higher-order structures within the interphase nucleus. One level of organization involves the formation of chromatin loops that may provide a favorable environment to processes such as DNA replication, transcription, and repair. However, little is known about the mechanistic basis of this structuration. Here we demonstrate that cohesin participates in the spatial organization of DNA replication factories in human cells. Cohesin is enriched at replication origins and interacts with prereplication complex proteins. Down-regulation of cohesin slows down S-phase progression by limiting the number of active origins and increasing the length of chromatin loops that correspond with replicon units. These results give a new dimension to the role of cohesin in the architectural organization of interphase chromatin, by showing its participation in DNA replication. © 2010 by Cold Spring Harbor Laboratory Press. Source

Irisarri I.,CSIC - National Museum of Natural Sciences | Mauro D.S.,University of Barcelona | Abascal F.,CSIC - National Museum of Natural Sciences | Abascal F.,Structural Computational Biology Group | And 3 more authors.
BMC Genomics | Year: 2012

Background: Understanding the causes underlying heterogeneity of molecular evolutionary rates among lineages is a long-standing and central question in evolutionary biology. Although several earlier studies showed that modern frogs (Neobatrachia) experienced an acceleration of mitochondrial gene substitution rates compared to non-neobatrachian relatives, no further characterization of this phenomenon was attempted. To gain new insights on this topic, we sequenced the complete mitochondrial genomes and nine nuclear loci of one pelobatoid (Pelodytes punctatus) and five neobatrachians, Heleophryne regis (Heleophrynidae), Lechriodus melanopyga (Limnodynastidae), Calyptocephalella gayi (Calyptocephalellidae), Telmatobius bolivianus (Ceratophryidae), and Sooglossus thomasseti (Sooglossidae). These represent major clades not included in previous mitogenomic analyses, and most of them are remarkably species-poor compared to other neobatrachians.Results: We reconstructed a fully resolved and robust phylogeny of extant frogs based on the new mitochondrial and nuclear sequence data, and dated major cladogenetic events. The reconstructed tree recovered Heleophryne as sister group to all other neobatrachians, the Australasian Lechriodus and the South American Calyptocephalella formed a clade that was the sister group to Nobleobatrachia, and the Seychellois Sooglossus was recovered as the sister group of Ranoides. We used relative-rate tests and direct comparison of branch lengths from mitochondrial and nuclear-based trees to demonstrate that both mitochondrial and nuclear evolutionary rates are significantly higher in all neobatrachians compared to their non-neobatrachian relatives, and that such rate acceleration started at the origin of Neobatrachia.Conclusions: Through the analysis of the selection coefficient (ω) in different branches of the tree, we found compelling evidence of relaxation of purifying selection in neobatrachians, which could (at least in part) explain the observed higher mitochondrial and nuclear substitution rates in this clade. Our analyses allowed us to discard that changes in substitution rates could be correlated with increased mitochondrial genome rearrangement or diversification rates observed in different lineages of neobatrachians. © 2012 Irisarri et al.; licensee BioMed Central Ltd. Source

Spiga F.M.,Ecole Polytechnique Federale de Lausanne | Maietta P.,Structural Computational Biology Group | Guiducci C.,Ecole Polytechnique Federale de Lausanne
ACS Combinatorial Science | Year: 2015

To address limitations in the production of DNA aptamers against small molecules, we introduce a DNA-based capture-SELEX (systematic evolution of ligands by exponential enrichment) protocol with long and continuous randomized library for more flexibility, coupled with in-stream direct-specificity monitoring via SPR and high throughput sequencing (HTS). Applying this capture-SELEX on tobramycin shows that target-specificity arises at cycle number 8, which is confirmed by sequence convergence in HTS analysis. Interestingly, HTS also shows that the most enriched sequences are already visible after only two capture-SELEX cycles. The best aptamers displayed KD of approximately 200 nM, similar to RNA and DNA-based aptamers previously selected for tobramycin. The lowest concentration of tobramycin detected on label-free SPR experiments with the selected aptamers is 20-fold smaller than the clinical range limit, demonstrating suitability for small-drug biosensing. © 2015 American Chemical Society. Source

Malinverni D.,Ecole Polytechnique Federale de Lausanne | Marsili S.,Structural Computational Biology Group | Barducci A.,Ecole Polytechnique Federale de Lausanne | de Los Rios P.,Ecole Polytechnique Federale de Lausanne
PLoS Computational Biology | Year: 2015

Hsp70s are a class of ubiquitous and highly conserved molecular chaperones playing a central role in the regulation of proteostasis in the cell. Hsp70s assist a myriad of cellular processes by binding unfolded or misfolded substrates during a complex biochemical cycle involving large-scale structural rearrangements. Here we show that an analysis of coevolution at the residue level fully captures the characteristic large-scale conformational transitions of this protein family, and predicts an evolutionary conserved–and thus functional–homo-dimeric arrangement. Furthermore, we highlight that the features encoding the Hsp70 dimer are more conserved in bacterial than in eukaryotic sequences, suggesting that the known Hsp70/Hsp110 hetero-dimer is a eukaryotic specialization built on a pre-existing template. © 2015 Malinverni et al. Source

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