Signature, a web server for taxonomic characterization of sequence samples using signature genes

Signature genes are genes that are unique to a taxonomic clade and are common within it. They contain a wealth of information about clade-specific processes and hold a strong evolutionary signal that can be used to phylogenetically characterize a set of sequences, such as a metagenomics sample. As signature genes are based on gene content, they provide a means to assess the taxonomic origin of a sequence sample that is complementary to sequence-based analyses. Here, we introduce Signature (http://www.cmbi.ru.nl/signature), a web server that identifies the signature genes in a set of query sequences, and therewith phylogenetically characterizes it. The server produces a list of taxonomic clades that share signature genes with the set of query sequences, along with an insightful image of the tree of life, in which the clades are color coded based on the number of signature genes present. This allows the user to quickly see from which part(s) of the taxonomy the query sequences likely originate

Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces

Contains fulltext : 89590.pdf (publisher's version ) (Open Access)BACKGROUND: Many newly detected point mutations are located in protein-coding regions of the human genome. Knowledge of their effects on the protein's 3D structure provides insight into the protein's mechanism, can aid the design of further experiments, and eventually can lead to the development of new medicines and diagnostic tools. RESULTS: In this article we describe HOPE, a fully automatic program that analyzes the structural and functional effects of point mutations. HOPE collects information from a wide range of information sources including calculations on the 3D coordinates of the protein by using WHAT IF Web services, sequence annotations from the UniProt database, and predictions by DAS services. Homology models are built with YASARA. Data is stored in a database and used in a decision scheme to identify the effects of a mutation on the protein's 3D structure and function. HOPE builds a report with text, figures, and animations that is easy to use and understandable for (bio)medical researchers. CONCLUSIONS: We tested HOPE by comparing its output to the results of manually performed projects. In all straightforward cases HOPE performed similar to a trained bioinformatician. The use of 3D structures helps optimize the results in terms of reliability and details. HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background

Analysis and validation of overall N-glycan conformation in Privateer

The oligosaccharides in N-glycosylation provide key structural and functional contributions to a glycoprotein. These contributions are dependent on the composition and overall conformation of the glycans. The Privateer software allows structural biologists to evaluate and improve the atomic structures of carbohydrates, including N-glycans; this software has recently been extended to check glycan composition through the use of glycomics data. Here, a broadening of the scope of the software to analyse and validate the overall conformation of N-glycans is presented, focusing on a newly compiled set of glycosidic linkage torsional preferences harvested from a curated set of glycoprotein models

The EMBRACE web service collection

The EMBRACE (European Model for Bioinformatics Research and Community Education) web service collection is the culmination of a 5-year project that set out to investigate issues involved in developing and deploying web services for use in the life sciences. The project concluded that in order for web services to achieve widespread adoption, standards must be defined for the choice of web service technology, for semantically annotating both service function and the data exchanged, and a mechanism for discovering services must be provided. Building on this, the project developed: EDAM, an ontology for describing life science web services; BioXSD, a schema for exchanging data between services; and a centralized registry (http://www.embraceregistry.net) that collects together around 1000 services developed by the consortium partners. This article presents the current status of the collection and its associated recommendations and standards definition

The cohesin acetylation cycle controls chromatin loop length through a PDS5A brake mechanism

Cohesin structures the genome through the formation of chromatin loops and by holding together the sister chromatids. The acetylation of cohesin’s SMC3 subunit is a dynamic process that involves the acetyltransferase ESCO1 and deacetylase HDAC8. Here we show that this cohesin acetylation cycle controls the three-dimensional genome in human cells. ESCO1 restricts the length of chromatin loops, and of architectural stripes emanating from CTCF sites. HDAC8 conversely promotes the extension of such loops and stripes. This role in controlling loop length turns out to be distinct from the canonical role of cohesin acetylation that protects against WAPL-mediated DNA release. We reveal that acetylation controls the interaction of cohesin with PDS5A to restrict chromatin loop length. Our data support a model in which this PDS5A-bound state acts as a brake that enables the pausing and restart of loop enlargement. The cohesin acetylation cycle hereby provides punctuation in the process of genome folding

3D-Beacons: decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modeling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank

West-Life: A Virtual Research Environment for structural biology

The West-Life project (https://about.west-life.eu/)is a Horizon 2020 project funded by the European Commission to provide data processing and data management services for the international community of structural biologists, and in particular to support integrative experimental approaches within the field of structural biology. It has developed enhancements to existing web services for structure solution and analysis, created new pipelines to link these services into more complex higher-level workflows, and added new data management facilities. Through this work it has striven to make the benefits of European e-Infrastructures more accessible to life-science researchers in general and structural biologists in particular

Homology modelling and spectroscopy, a never-ending love story

Homology modelling is normally the technique of choice when experimental structure data are not available but three-dimensional coordinates are needed, for example, to aid with detailed interpretation of results of spectroscopic studies. Herein, the state of the art of homology modelling will be described in the light of a series of recent developments, and an overview will be given of the problems and opportunities encountered in this field. The major topic, the accuracy and precision of homology models, will be discussed extensively due to its influence on the reliability of conclusions drawn from the combination of homology models and spectroscopic data. Three real-world examples will illustrate how both homology modelling and spectroscopy can be beneficial for (bio)medical research

The CCP4 suite: integrative software for macromolecular crystallography

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.Jon Agirre is a Royal Society University Research Fellow (UF160039 and URF\R\221006). Mihaela Atanasova is funded by the UK Engineering and Physical Sciences Research Council (EPSRC; EP/R513386/1). Haroldas Bagdonas is funded by The Royal Society (RGF/R1/181006). Jose´ Javier Burgos-Ma´rmol and Daniel J. Rigden are supported by the BBSRC (BB/S007105/1). Robbie P. Joosten is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 871037 (iNEXTDiscovery) and by CCP4. This work was supported by the Medical Research Council as part of United Kingdom Research and Innovation, also known as UK Research and Innovation: MRC file reference No. MC_UP_A025_1012 to Garib N. Murshudov, which also funded Keitaro Yamashita, Paul Emsley and Fei Long. Robert A. Nicholls is funded by the BBSRC (BB/S007083/1). Soon Wen Hoh is funded by the BBSRC (BB/T012935/1). Kevin D. Cowtan and Paul S. Bond are funded in part by the BBSRC (BB/S005099/1). John Berrisford and Sameer Velankar thank the European Molecular Biology Laboratory–European Bioinformatics Institute, who supported this work. Andrea Thorn was supported in the development of AUSPEX by the German Federal Ministry of Education and Research (05K19WWA and 05K22GU5) and by Deutsche Forschungsgemeinschaft (TH2135/2-1). Petr Kolenko and Martin Maly´ are funded by the MEYS CR (CZ.02.1.01/0.0/0.0/16_019/0000778). Martin Maly´ is funded by the Czech Academy of Sciences (86652036) and CCP4/STFC (521862101). Anastassis Perrakis acknowledges funding from iNEXT (grant No. 653706), iNEXT-Discovery (grant No. 871037), West-Life (grant No. 675858) and EOSC-Life (grant No. 824087) funded by the Horizon 2020 program of the European Commission. Robbie P. Joosten has been the recipient of a Veni grant (722.011.011) and a Vidi grant (723.013.003) from the Netherlands Organization for Scientific Research (NWO). Maarten L. Hekkelman, Robbie P. Joosten and Anastassis Perrakis thank the Research High Performance Computing facility of the Netherlands Cancer Institute for providing and maintaining computation resources and acknowledge the institutional grant from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Tarik R. Drevon is funded by the BBSRC (BB/S007040/1). Randy J. Read is supported by a Principal Research Fellowship from the Wellcome Trust (grant 209407/Z/17/Z). Atlanta G. Cook is supported by a Wellcome Trust SRF (200898) and a Wellcome Centre for Cell Biology core grant (203149). Isabel Uso´n acknowledges support from STFC-UK/CCP4: ‘Agreement for the integration of methods into the CCP4 software distribution, ARCIMBOLDO_LOW’ and Spanish MICINN/AEI/FEDER/UE (PID2021-128751NB-I00). Pavol Skubak and Navraj Pannu were funded by the NWO Applied Sciences and Engineering Domain and CCP4 (grant Nos. 13337 and 16219). Bernhard Lohkamp was supported by the Ro¨ntgen A˚ ngstro¨m Cluster (grant 349-2013-597). Nicholas Pearce is currently funded by the SciLifeLab and Wallenberg Data Driven Life Science Program (grant KAW 2020.0239) and has previously been funded by a Veni Fellowship (VI.Veni.192.143) from the Dutch Research Council (NWO), a Long-term EMBO fellowship (ALTF 609-2017) and EPSRC grant EP/G037280/1. David M. Lawson received funding from BBSRC Institute Strategic Programme Grants (BB/P012523/1 and BB/P012574/1). Lucrezia Catapano is the recipient of an STFC/CCP4-funded PhD studentship (Agreement No: 7920 S2 2020 007).Peer reviewe

The CCP4 suite : integrative software for macromolecular crystallography

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world