Template Choice Research Articles

Prompt for extraction: Multiple templates choice model for event extraction

Prompt for extraction: Multiple templates choice model for event extraction

Recombinase-independent chromosomal rearrangements between dispersed inverted repeats in Saccharomyces cerevisiae meiosis.

DNA double-strand break (DSB) repair by homologous recombination (HR) uses a DNA template with similar sequence to restore genetic identity. Allelic DNA repair templates can be found on the sister chromatid or homologous chromosome. During meiotic recombination, DSBs preferentially repair from the homologous chromosome, with a proportion of HR events generating crossovers. Nevertheless, regions of similar DNA sequence exist throughout the genome, providing potential DNA repair templates. When DSB repair occurs at these non-allelic loci (termed ectopic recombination), chromosomal duplications, deletions and rearrangements can arise. Here, we characterize in detail ectopic recombination arising between a dispersed pair of inverted repeats in wild-type Saccharomyces cerevisiae at both a local and a chromosomal scale-the latter identified via gross chromosomal acentric and dicentric chromosome rearrangements. Mutation of the DNA damage checkpoint clamp loader Rad24 and the RecQ helicase Sgs1 causes an increase in ectopic recombination. Unexpectedly, additional mutation of the RecA orthologues Rad51 and Dmc1 alters-but does not abolish-the type of ectopic recombinants generated, revealing a novel class of inverted chromosomal rearrangement driven by the single-strand annealing pathway. These data provide important insights into the role of key DNA repair proteins in regulating DNA repair pathway and template choice during meiosis.

Chromatin landscape, DSB levels, and cKU-70/80 contribute to patterning of meiotic DSB processing along chromosomes in C. elegans.

Programmed DNA double-strand break (DSB) formation is essential for achieving accurate chromosome segregation during meiosis. DSB repair timing and template choice are tightly regulated. However, little is known about how DSB distribution and the choice of repair pathway are regulated along the length of chromosomes, which has direct effects on the recombination landscape and chromosome remodeling at late prophase I. Here, we use the spatiotemporal resolution of meiosis in the Caenorhabditis elegans germline along with genetic approaches to study distribution of DSB processing and its regulation. High-resolution imaging of computationally straightened chromosomes immunostained for the RAD-51 recombinase marking DSB repair sites reveals that the pattern of RAD-51 foci throughout pachytene resembles crossover distribution in wild type. Specifically, RAD-51 foci occur primarily along the gene-poor distal thirds of the chromosomes in both early and late pachytene, and on both the X and the autosomes. However, this biased off-center distribution can be abrogated by the formation of excess DSBs. Reduced condensin function, but not an increase in total physical axial length, results in a homogeneous distribution of RAD-51 foci, whereas regulation of H3K9 methylation is required for the enrichment of RAD-51 at off-center positions. Finally, the DSB recognition heterodimer cKU-70/80, but not the non-homologous end-joining canonical ligase LIG-4, contributes to the enriched off-center distribution of RAD-51 foci. Taken together, our data supports a model by which regulation of the chromatin landscape, DSB levels, and DSB detection by cKU-70/80 collaborate to promote DSB processing by homologous recombination at off-center regions of the chromosomes in C. elegans.

Registration quality filtering improves robustness of voxel-wise analyses to the choice of brain template

Motivation:Many clinical and scientific conclusions that rely on voxel-wise analyses of neuroimaging depend on the accurate comparison of corresponding anatomical regions. Such comparisons are made possible by registration of the images of subjects of interest onto a common brain template, such as the Johns Hopkins University (JHU) template. However, current image registration algorithms are prone to errors that are distributed in a template-dependent manner. Therefore, the results of voxel-wise analyses can be sensitive to template choice. Despite this problem, the issue of appropriate template choice for voxel-wise analyses is not generally addressed in contemporary neuroimaging studies, which may lead to the reporting of spurious results.Results:We present a novel approach to determine the suitability of a brain template for voxel-wise analysis. The approach is based on computing a “distance” between automatically-generated atlases of the subjects of interest and templates that is indicative of the extent of subject-to-template registration errors. This allows for the filtering of subjects and candidate templates based on a quantitative measure of registration quality. We benchmark our approach by evaluating alternative templates for a voxel-wise analysis that reproduces the well-known decline in fractional anisotropy (FA) with age. Our results show that filtering registrations minimizes errors and decreases the sensitivity of voxel-wise analysis to template choice. In addition to carrying important implications for future neuroimaging studies, the developed framework of template induction can be used to evaluate robustness of data analysis methods to template choice.

Non-Linear Template-Based Approach for the Study of Locomotion.

The automatic detection of gait events (i.e., Initial Contact (IC) and Final Contact (FC)) is crucial for the characterisation of gait from Inertial Measurements Units. In this article, we present a method for detecting steps (i.e., IC and FC) from signals of gait sequences of individuals recorded with a gyrometer. The proposed approach combines the use of a dictionary of templates and a Dynamic Time Warping (DTW) measure of fit to retrieve these templates into input signals. Several strategies for choosing and learning the adequate templates from annotated data are also described. The method is tested on thirteen healthy subjects and compared to gold standard. Depending of the template choice, the proposed algorithm achieves average errors from 0.01 to 0.03 s for the detection of IC, FC and step duration. Results demonstrate that the use of DTW allows achieving these performances with only one single template. DTW is a convenient tool to perform pattern recognition on gait gyrometer signals. This study paves the way for new step detection methods: it shows that using one single template associated with non-linear deformations may be sufficient to model the gait of healthy subjects.

Chromosome Preference During Homologous Recombination Repair of DNA Double-Strand Breaks in Drosophila melanogaster.

DNA double-strand breaks (DSBs) are especially toxic DNA lesions that, if left unrepaired, can lead to wide-ranging genomic instability. Of the pathways available to repair DSBs, the most accurate is homologous recombination (HR), where a homologous sequence is used as a donor template to restore genetic information at the break site. While much of the biochemical aspects of HR repair have been characterized, how the repair machinery locates and discriminates between potential homologous donor templates throughout the genome remains elusive. We use Drosophila melanogaster to investigate whether there is a preference between intrachromosomal and interhomolog donor sequences in mitotically dividing cells. Our results demonstrate that, although interhomolog HR is possible and frequent if another donor template is not available, intrachromosomal donor templates are highly preferred. This is true even if the interhomolog donor template is less diverged than the intrachromosomal donor template. Thus, despite the stringent requirements for homology, the chromosomal location of the donor template plays a more significant role in donor template choice.

Dead or Alive; or Does It Really Matter? Level of Congruency Between Trophic Modes in Total and Active Fungal Communities in High Arctic Soil.

Describing dynamics of belowground organisms, such as fungi, can be challenging. Results of studies based on environmental DNA (eDNA) may be biased as the template does not discriminate between metabolically active cells and dead biomass. We analyzed ribosomal DNA (rDNA) and ribosomal RNA (rRNA) coextracted from 48 soil samples collected from a manipulated snow depth experiment in two distinct vegetation types in Svalbard, in the High Arctic. Our main goal was to compare if the rDNA and rRNA metabarcoding templates produced congruent results that would lead to consistent ecological interpretation. Data derived from both rDNA and rRNA clustered according to vegetation types. Different sets of environmental variables explained the community composition based on the metabarcoding template. rDNA and rRNA-derived community composition of symbiotrophs and saprotrophs, unlike pathotrophs, clustered together in a similar way as when the community composition was analyzed using all OTUs in the study. Mean OTU richness was higher for rRNA, especially in symbiotrophs. The metabarcoding template was more important than vegetation type in explaining differences in richness. The proportion of symbiotrophic, saprotrophic and functionally unassigned reads differed between rDNA and rRNA, but showed similar trends. There was no evidence for increased snow depth influence on fungal community composition or richness. Our findings suggest that template choice may be especially important for estimating biodiversity, such as richness and relative abundances, especially in Helotiales and Agaricales, but not for inferring community composition. Differences in study results originating from rDNA or rRNA may directly impact the ecological conclusions of one’s study, which could potentially lead to false conclusions on the dynamics of microbial communities in a rapidly changing Arctic.

Dependence of Optical Active Galactic Nuclei Identification on Stellar Population Models

Abstract We have conducted a study to quantify the systematic differences resulting from using different stellar population models (SPM) in optical spectroscopic identification of type II active galactic nuclei (AGNs). We examined the different AGN detection fractions of 7069 nearby galaxies (z ≤ 0.09) with Sloan Digital sky Survey (SDSS) DR8 spectra when using the Bruzual & Charlot (BC03), Vazdekis et al. (MILES), and solar metallicity Maraston & Strömbäck (MS11solar) SPM. The line fluxes obtained using BC03 and MS11solar are publicly available from SDSS data releases. We find that the BC03 templates result in systematically higher BPT line ratios and consequently higher AGN fractions, and the MS11solar templates result in systematically lower line ratios and AGN fractions compared with the MILES templates. Using MILES as the standard, BC03 results in 25% “false positives” and MS11solar results in 22% “false negatives” when using the Kewley et al. boundary for AGN identification. The fraction of galaxies whose AGN identification changes for different templates is luminosity dependent, ranging from a few percent for L [O iii]5007 ≥ 1040 erg s−1 and increasing to ∼50% for L [O iii]5007 ≤ 1038 erg s−1. These results suggest that template choice should be accounted for when using and comparing the AGN and emission line fluxes from different catalogs.

Combined Virtual and Experimental Screening for CK1 Inhibitors Identifies a Modulator of p53 and Reveals Important Aspects of in Silico Screening Performance

A compound collection of pronounced structural diversity was comprehensively screened for inhibitors of the DNA damage-related kinase CK1. The collection was evaluated in vitro. A potent and selective CK1 inhibitor was discovered and its capacity to modulate the endogenous levels of the CK1-regulated tumor suppressor p53 was demonstrated in cancer cell lines. Administration of 10 μM of the compound resulted in significant increase of p53 levels, reaching almost 2-fold in hepatocellular carcinoma cells. In parallel to experimental screening, two representative and orthogonal in silico screening methodologies were implemented for enabling the retrospective assessment of virtual screening performance on a case-specific basis. Results showed that both techniques performed at an acceptable and fairly comparable level, with a slight advantage of the structure-based over the ligand-based approach. However, both approaches demonstrated notable sensitivity upon parameters such as screening template choice and treatment of redundancy in the enumerated compound collection. An effort to combine insight derived by sequential implementation of the two methods afforded poor further improvement of screening performance. Overall, the presented assessment highlights the relation between improper use of enrichment metrics and misleading results, and demonstrates the inherent delicacy of in silico methods, emphasizing the challenging character of virtual screening protocol optimization.

Improvising 5-HT7R homology model for design of high affinity ligands: model validation with docking, embrace minimization, MM-GBSA, and molecular dynamic simulations

The subtype, 5-HT7R has been implicated in neurological disorders and presents itself as a promising target for antidepressant drugs. Design of targeted selective ligands, require a sound knowledge of 3D-receptor structure. In absence of receptor structure, structure-based design of targeted ligands relies on generation of 5-HT7R homology model. In this study, the impact of template choice, alignment, and model building methods on the homology model of 5-HT7R is addressed. The compactness and model quality due to the presence of cholesterol (lipidic receptor) have also been observed. The results suggest good stereochemical quality of the final model. Ramachandran Plot Analysis indicated more than 97.5% amino acid residues in the favorable region. The overall quality factor was 91.8% using ERRAT. The Z-score for backbone confirmation and packing quality were −1.248 and −1.427, respectively, using WHATCHECK. The RMS Z-score for side chain planarity was .711. Other validation results for the final model include binding site analysis in which Asp162, Val163, Phe343, Phe344, Arg350, Arg367, and Leu370 conserved residues were found in the active site, correlation coefficient of .82 in ligand-based screening and .85 in embrace minimization. Further, the model showed good correlation for agonist and antagonist in docking ( ≈ .76, ≈ .82), embrace minimization ( ≈ .73, ≈ .72), and MM-GBSA ( ≈ .69, ≈ .75) studies. The model was subjected to Molecular Dynamics (MD) simulation of 20 ns both in ligand-free and ligand-bound receptor (agonist and antagonist) system in order to assess its stability.

U6 snRNA Pseudogenes: Markers of Retrotransposition Dynamics in Mammals.

Transposable elements comprise more than 45% of the human genome and long interspersed nuclear element 1 (LINE-1 or L1) is the only autonomous mobile element remaining active. Since its identification, it has been proposed that L1 contributes to the mobilization and amplification of other cellular RNAs and more recently, experimental demonstrations of this function has been described for many transcripts such as Alu, a nonautonomous mobile element, cellular mRNAs, or small noncoding RNAs. Detailed examination of the mobilization of various cellular RNAs revealed distinct pathways by which they could be recruited during retrotransposition; template choice or template switching. Here, by analyzing genomic structures and retrotransposition signatures associated with small nuclear RNA (snRNA) sequences, we identified distinct recruiting steps during the L1 retrotransposition cycle for the formation of snRNA-processed pseudogenes. Interestingly, some of the identified recruiting steps take place in the nucleus. Moreover, after comparison to other vertebrate genomes, we established that snRNA amplification by template switching is common to many LINE families from several LINE clades. Finally, we suggest that U6 snRNA copies can serve as markers of L1 retrotransposition dynamics in mammalian genomes.

Impact of template choice on homology model efficiency in virtual screening.

Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, only the closest ones are chosen for homology modeling purposes. To validate the aforementioned approach, we performed homology modeling of four serotonin receptors (5-HT1AR, 5-HT2AR, 5-HT6R, 5-HT7R) for virtual screening purposes, using 10 available G-Protein Coupled Receptors (GPCR) templates with diverse evolutionary distances to the targets, with various approaches to alignment construction and model building. The resulting models were further validated in two steps by means of ligand docking and enrichment calculation, using Glide software. The final quality of the models was determined in virtual screening-like experiments by the AUROC score of the resulting ROC curves. The outcome of this research showed that no correlation between sequence identity and model quality was found, leading to the conclusion that the closest phylogenetic relative is not always the best template for homology modeling.

The Sense and Sensibility of Strand Exchange in Recombination Homeostasis

The Sense and Sensibility of Strand Exchange in Recombination Homeostasis

GOMoDo: A GPCRs online modeling and docking webserver.

G-protein coupled receptors (GPCRs) are a superfamily of cell signaling membrane proteins that include >750 members in the human genome alone. They are the largest family of drug targets. The vast diversity and relevance of GPCRs contrasts with the paucity of structures available: only 21 unique GPCR structures have been experimentally determined as of the beginning of 2013. User-friendly modeling and small molecule docking tools are thus in great demand. While both GPCR structural predictions and docking servers exist separately, with GOMoDo (GPCR Online M odeling and D ocking), we provide a web server to seamlessly model GPCR structures and dock ligands to the models in a single consistent pipeline. GOMoDo can automatically perform template choice, homology modeling and either blind or information-driven docking by combining together proven, state of the art bioinformatic tools. The web server gives the user the possibility of guiding the whole procedure. The GOMoDo server is freely accessible at http://molsim.sci.univr.it/gomodo.

The importance of template choice in homology modeling. A 5-HT6R case study

Over the years, homology modelling has grown into an important tool for biochemistry and pharmacology. It allows prediction of three-dimensional structure of proteins, which have not been resolved with empirical methods. The final outcome of such research is affected by many factors, the choice of template being a crucial one. Current paradigm states, that proteins with the smallest evolutionary distance and thus, the highest identity/similarity, to the target, should achieve the highest performance. The goal of this research was to verify the credibility of this assumption when incorporating homology models into Virtual Screening protocol. The target for this case study is 5-HT6R, which belongs to class A GPCR, and as a trans-membrane protein, is extremely hard to crystallize or solubilize. This makes standard protein structure assessment inexplicably difficult, however a few members of class A GPCR had their structure solved. 5-HT6R itself is involved in learning, memorizing and overall cognition processes, and is a target in anti-depression drug research [1,2]. This study comprised of homology modelling of 5-HT6R based on seven available GPCR templates (A2A, beta1, beta2, CXCR4, D3, H1, rhodopsin), and further verification of created models by means of ligand docking (Glide). The quality of generated structures was assessed in three subsequent steps, each consisting of different compounds sets for docking procedure. The final models were selected basing on the number of active ligands to decoys docked ratio. Interestingly, the templates used to construct the most successful models were not the evolutionarily closest ones, therefore putting the existing paradigm into question when it comes to VS application.

Assessment of 3D models for allergen research

Allergenic proteins must crosslink specific IgE molecules, bound to the surface of mast cells and basophils, to stimulate an immune response. A structural understanding of the allergen-IgE interface is needed to predict cross-reactivities between allergens and to design hypoallergenic proteins. However, there are less than 90 experimentally determined structures available for the approximately 1500 sequences of allergens and isoallergens cataloged in the Structural Database of Allergenic Proteins. To provide reliable structural data for the remaining proteins, we previously produced more than 500 3D models using an automated procedure, with strict controls on template choice and model quality evaluation. Here, we assessed how well the fold and residue surface exposure of 10 of these models correlated with recently published experimental 3D structures determined by X-ray crystallography or NMR. We also discuss the impact of intrinsically disordered regions on the structural comparison and epitope prediction. Overall, for seven allergens with sequence identities to the original templates higher than 27%, the backbone root-mean square deviations were less than 2 Å between the models and the subsequently determined experimental structures for the ordered regions. Further, the surface exposure of the known IgE epitopes on the models of three major allergens, from peanut (Ara h 1), latex (Hev b 2), and soy (Gly m 4), was very similar to the experimentally determined structures. For the three remaining allergens with lower sequence identities to the modeling templates, the 3D folds were correctly identified. However, the accuracy of those models is not sufficient for a reliable epitope mapping.

Influence of DNA Template Choice on Transcription and Inhibition of Escherichia coli RNA Polymerase

In recent decades, quantitative transcription assays using bacterial RNA polymerase (RNAP) have been performed under widely diverse experimental conditions. We demonstrate that the template choice can influence the inhibitory potency of RNAP inhibitors. Furthermore, we illustrate that the sigma factor (σ(70)) surprisingly increases the transcription efficiency of templates with nonphysiological nonprokaryotic promoters. Our results might be a useful guideline in the early stages of using RNAP for drug discovery.

Correlation‐based visual odometry for ground vehicles

AbstractReliable motion estimation is a key component for autonomous vehicles. We present a visual odometry method for ground vehicles using template matching. The method uses a downward‐facing camera perpendicular to the ground and estimates the motion of the vehicle by analyzing the image shift from frame to frame. Specifically, an image region (template) is selected, and using correlation we find the corresponding image region in the next frame. We introduce the use of multitemplate correlation matching and suggest template quality measures for estimating the suitability of a template for the purpose of correlation. Several aspects of the template choice are also presented. Through an extensive analysis, we derive the expected theoretical error rate of our system and show its dependence on the template window size and image noise. We also show how a linear forward prediction filter can be used to limit the search area to significantly increase the computation performance. Using a single camera and assuming an Ackerman‐steering model, the method has been implemented successfully on a large industrial forklift and a 4×4 vehicle. Over 6 km of field trials from our industrial test site, an off‐road area and an urban environment are presented illustrating the applicability of the method as an independent sensor for large vehicle motion estimation at practical velocities. © 2011 Wiley Periodicals, Inc.

The template choice decision in meiosis: is the sister important?

Recombination between homologous chromosomes is crucial to ensure their proper segregation during meiosis. This is achieved by regulating the choice of recombination template. In mitotic cells, double-strand break repair with the sister chromatid appears to be preferred, whereas interhomolog recombination is favoured during meiosis. However, in the last year, several studies in yeast have shown the importance of the meiotic recombination between sister chromatids. Although this thinking seems to be new, evidences for sister chromatid exchange during meiosis were obtained more than 50 years ago in non-model organisms. In this mini-review, we comment briefly on the most recent advances in this hot topic and also describe observations which suggest the existence of inter-sister repair during meiotic recombination. For instance, the behaviour of mammalian XY bivalents and that of trivalents in heterozygotes for chromosomal rearrangements are cited as examples. The "rediscovering" of the requirement for the sister template, although it seems to occur at a low frequency, will probably prompt further investigations in organisms other than yeast to understand the complexity of the partner choice during meiosis.

Pt/TiO2 Growth Templates for Enhanced PZT films and MEMS Devices

ABSTRACTThe crystallographic texture of lead zirconate titanate (PZT) thin films strongly influences the piezoelectric properties used in MEMS applications. For PZT films poled to saturation, the piezoelectric response is sequentially greater for random, {111}, and {001} texture. Textured growth can be achieved by relying on crystal growth habit and can also be initiated by the use of a seed layer that provides a heteroepitaxial template. Template choice and the process used to form it determine the structural quality and ultimately influence performance and reliability of MEMS PZT devices such as switches, filters, and actuators. This study focuses on how {111}-textured PZT is generated by a combination of crystal habit and templating mechanisms that occur in the PZT/bottom-electrode stack. The sequence begins with {0001}-textured Ti deposited on thermally grown SiO2 on a Si wafer. The Ti is converted to {100}-textured TiO2 (rutile) through thermal oxidation. Then {111}-textured Pt can be grown to act as a template for {111}-textured PZT. The Ti and Pt are deposited by DC magnetron sputtering. The TiO2 and Pt film textures and structure were optimized by variation of sputtering deposition times, temperatures and power levels, and post-deposition anneal conditions. The relationship between Ti, TiO2, and Pt texture and their impact on PZT growth will be presented.