Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to ...state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission.
Determining the structure and function of a novel protein is a cornerstone of many aspects of modern biology. Over the past decades, a number of computational tools for structure prediction have been ...developed. It is critical that the biological community is aware of such tools and is able to interpret their results in an informed way. This protocol provides a guide to interpreting the output of structure prediction servers in general and one such tool in particular, the protein homology/analogy recognition engine (Phyre). New profile-profile matching algorithms have improved structure prediction considerably in recent years. Although the performance of Phyre is typical of many structure prediction systems using such algorithms, all these systems can reliably detect up to twice as many remote homologies as standard sequence-profile searching. Phyre is widely used by the biological community, with >150 submissions per day, and provides a simple interface to results. Phyre takes 30 min to predict the structure of a 250-residue protein.
A big challenge in current systems biology research arises when different types of data must be accessed from separate sources and visualized using separate tools. The high cognitive load required to ...navigate such a workflow is detrimental to hypothesis generation. Accordingly, there is a need for a robust research platform that incorporates all data and provides integrated search, analysis, and visualization features through a single portal. Here, we present ePlant (http://bar.utoronto.ca/eplant), a visual analytic tool for exploring multiple levels of Arabidopsis thaliana data through a zoomable user interface. ePlant connects to several publicly available web services to download genome, proteome, interactome, transcriptome, and 3D molecular structure data for one or more genes or gene products of interest. Data are displayed with a set of visualization tools that are presented using a conceptual hierarchy from big to small, and many of the tools combine information from more than one data type. We describe the development of ePlant in this article and present several examples illustrating its integrative features for hypothesis generation. We also describe the process of deploying ePlant as an “app” on Araport. Building on readily available web services, the code for ePlant is freely available for any other biological species research.
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Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we ...performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of hESCs representing each of the three embryonic germ layers. Integration of whole-genome bisulfite sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing reveals unique events associated with specification toward each lineage. Lineage-specific dynamic alterations in DNA methylation and H3K4me1 are evident at putative distal regulatory elements that are frequently bound by pluripotency factors in the undifferentiated hESCs. In addition, we identified germ-layer-specific H3K27me3 enrichment at sites exhibiting high DNA methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches, leading to more faithful differentiation strategies as well as providing insights into the rewiring of human regulatory programs during cellular transitions.
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•Epigenetic and transcriptional dynamics in hESCs and hESC-derived populations•Lineage-specific remodeling at regions bound by OCT4, SOX2, and NANOG in hESCs•Germ-layer-specific switch to H3K4me1 or H3K27me3 at sites of high DNA methylation•Epigenetic dynamics frequently precede transcriptional activation
The epigenetic and transcriptional landscapes of three cell types representing each embryonic lineage derived from human embryonic stem cells are profiled, revealing distinct histone modification and DNA methylation dynamics that accompany lineage specification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surgery for isolated tricuspid valve (TV) disease remains relatively infrequent because of significant patient comorbidities and poor surgical outcomes. This study reviewed the experience with ...isolated TV surgery in the current era to determine whether outcomes have improved.
From 2007 through 2017, 685 TV operations were performed in a single institution, of which 95 (13.9%) operations were isolated TV surgery. Patients were analyzed for disease origin, risk factors, operative mortality and morbidity, and long-term survival.
A total of 95 patients underwent isolated TV surgery, an average of 9 patients per year increasing from an average of 5 per year to 15 per year during the study period. Surgery was reoperative in 41% (38 of 95) of patients, including 11.6% (11 of 95) with prior coronary artery bypass grafting and 29.4% (28 of 95) with prior valve surgery (9 TV, 11 mitral, 2 aortic, 5 mitral and aortic, and 1 mitral and TV). Repair was performed in 71.6% (68 of 95) of patients, and replacement was performed in 28.4% (27 of 95). Operative mortality was 3.2% (3 of 95), with no mortality in the most recent 73 patients over the last 6 years. Stroke occurred in 2.1% (2 of 95) of patients, acute kidney injury requiring dialysis in 5.3% (5 of 95), and the need for new permanent pacemaker in 16.8% (16 of 95).
In the current era with careful patient selection and periprocedural management, isolated TV surgery can be performed with lower morbidity and mortality than has traditionally been reported with good long-term survival. These outcomes can also serve as a benchmark for catheter-based TV intervention outcomes.
ABSTRACT
We combine orbital information from N-body simulations with an analytic model for star formation quenching and SDSS observations to infer the differential effect of the group/cluster ...environment on star formation in satellite galaxies. We also consider a model for gas stripping, using the same input supplemented with H i fluxes from the ALFALFA survey. The models are motivated by and tested on the Hydrangea cosmological hydrodynamical simulation suite. We recover the characteristic times when satellite galaxies are stripped and quenched. Stripping in massive ($M_{\rm vir}\sim 10^{14.5}\, {\rm M}_\odot$) clusters typically occurs at or just before the first pericentric passage. Lower mass ($\sim 10^{13.5}\, {\rm M}_\odot$) groups strip their satellites on a significantly longer (by $\sim 3\, {\rm Gyr}$) time-scale. Quenching occurs later: Balmer emission lines typically fade $\sim 3.5\, {\rm Gyr}$ ($5.5\, {\rm Gyr}$) after first pericentre in clusters (groups), followed a few hundred Myr later by reddenning in (g − r) colour. These ‘delay time-scales’ are remarkably constant across the entire satellite stellar mass range probed (∼109.5–$10^{11}\, {\rm M}_\odot$), a feature closely tied to our treatment of ‘group pre-processing’. The lowest mass groups in our sample ($\sim 10^{12.5}\, {\rm M}_\odot$) strip and quench their satellites extremely inefficiently: typical time-scales may approach the age of the Universe. Our measurements are qualitatively consistent with the ‘delayed-then-rapid’ quenching scenario advocated for by several other studies, but we find significantly longer delay times. Our combination of a homogeneous analysis and input catalogues yields new insight into the sequence of events leading to quenching across wide intervals in host and satellite mass.
3DLigandSite is a web server for the prediction of ligand-binding sites. It is based upon successful manual methods used in the eighth round of the Critical Assessment of techniques for protein ...Structure Prediction (CASP8). 3DLigandSite utilizes protein-structure prediction to provide structural models for proteins that have not been solved. Ligands bound to structures similar to the query are superimposed onto the model and used to predict the binding site. In benchmarking against the CASP8 targets 3DLigandSite obtains a Matthew's correlation co-efficient (MCC) of 0.64, and coverage and accuracy of 71 and 60%, respectively, similar results to our manual performance in CASP8. In further benchmarking using a large set of protein structures, 3DLigandSite obtains an MCC of 0.68. The web server enables users to submit either a query sequence or structure. Predictions are visually displayed via an interactive Jmol applet. 3DLigandSite is available for use at http://www.sbg.bio.ic.ac.uk/3dligandsite.
Whole-genome and exome sequencing studies reveal many genetic variants between individuals, some of which are linked to disease. Many of these variants lead to single amino acid variants (SAVs), and ...accurate prediction of their phenotypic impact is important. Incorporating sequence conservation and network-level features, we have developed a method, SuSPect (Disease-Susceptibility-based SAV Phenotype Prediction), for predicting how likely SAVs are to be associated with disease. SuSPect performs significantly better than other available batch methods on the VariBench benchmarking dataset, with a balanced accuracy of 82%. SuSPect is available at www.sbg.bio.ic.ac.uk/suspect. The Web site has been implemented in Perl and SQLite and is compatible with modern browsers. An SQLite database of possible missense variants in the human proteome is available to download at www.sbg.bio.ic.ac.uk/suspect/download.html.
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•Bioinformatics approaches are key for identification of disease-causing variants.•SAV phenotype prediction can be improved using network information.•A method including these features, SuSPect, outperforms tested methods.•SuSPect is available to use at www.sbg.bio.ic.ac.uk/suspect.
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Hydrothermal vents and the origin of life Martin, William; Baross, John; Kelley, Deborah ...
Nature reviews. Microbiology,
11/2008, Volume:
6, Issue:
11
Journal Article
Peer reviewed
Submarine hydrothermal vents are geochemically reactive habitats that harbour rich microbial communities. There are striking parallels between the chemistry of the H(2)-CO(2) redox couple that is ...present in hydrothermal systems and the core energy metabolic reactions of some modern prokaryotic autotrophs. The biochemistry of these autotrophs might, in turn, harbour clues about the kinds of reactions that initiated the chemistry of life. Hydrothermal vents thus unite microbiology and geology to breathe new life into research into one of biology's most important questions - what is the origin of life?
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