Watson Buchanan
Ontology highlight
ABSTRACT:
SUBMITTER: Nuki G
PROVIDER: S-EPMC1463929 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Geometrical restraints provide key structural information for the determination of biomolecular structures at lower resolution by experimental methods such as crystallography or cryo-electron microscopy. In this work, restraint targets for nucleic acids bases are derived from three different sources and compared: small-molecule crystal structures in the Cambridge Structural Database (CSD), ultrahigh-resolution structures in the Protein Data Bank (PDB) and quantum-mechanical (QM) calculations. The best parameters are those based on CSD structures. After over two decades, the standard library of Parkinson et al. [(1996), Acta Cryst. D52, 57-64] is still valid, but improvements are possible with the use of the current CSD database. The CSD-derived geometry is fully compatible with Watson-Crick base pairs, as comparisons with QM results for isolated and paired bases clearly show that the CSD targets closely correspond to proper base pairing. While the QM results are capable of distinguishing between single and paired bases, their level of accuracy is, on average, nearly two times lower than for the CSD-derived targets when gauged by root-mean-square deviations from ultrahigh-resolution structures in the PDB. Nevertheless, the accuracy of QM results appears sufficient to provide stereochemical targets for synthetic base pairs where no reliable experimental structural information is available. To enable future tests for this approach, QM calculations are provided for isocytosine, isoguanine and the iCiG base pair.
| S-EPMC6457083 | biostudies-literature
Project description:We report our experiences with minimally invasive total hip replacement performed via a modified Watson-Jones approach with a special positioning technique (the "Stolzalpe technique"). With the patient placed in the conventional supine position, the contralateral leg is held in a gynaecological footrest to allow hyperextension, adduction and external rotation of the leg during femoral preparation. The first 117 patients operated with this technique were compared with a conventionally operated group. The patients operated with the Stolzalpe technique had superior results for nearly all study criteria, including time of operation, time of postoperative intensive care, blood loss, complications and Harris Hip Score. The Stolzalpe technique appears to be the best possible compromise between patient comfort and the surgical demands of proper implant positioning, minimization of anaesthetic risk, and reducing the time required for draping and positioning.
| S-EPMC2267521 | biostudies-other
Project description:A glacial-fed river delta contains viable and potentially active methanogens and sulfate reducers.
| PRJEB14184 | ENA
Project description:In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase ? variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G • T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA.
| S-EPMC3033279 | biostudies-literature
Project description:Background: Oncologists increasingly rely on clinical genome sequencing to pursue effective, molecularly targeted therapies. This study assesses the validity and utility of the artificial intelligence Watson for Genomics (WfG) for analyzing clinical sequencing results. Methods: This study identified patients with solid tumors who participated in in-house genome sequencing projects at a single cancer specialty hospital between April 2013 and October 2016. Targeted genome sequencing results of these patients' tumors, previously analyzed by multidisciplinary specialists at the hospital, were reanalyzed by WfG. This study measures the concordance between the two evaluations. Results: In 198 patients, in-house genome sequencing detected 785 gene mutations, 40 amplifications, and 22 fusions after eliminating single nucleotide polymorphisms. Breast cancer (n = 40) was the most frequent diagnosis in this analysis, followed by gastric cancer (n = 31), and lung cancer (n = 30). Frequently detected single nucleotide variants were found in TP53 (n = 107), BRCA2 (n = 24), and NOTCH2 (n = 23). MYC (n = 10) was the most frequently detected gene amplification, followed by ERBB2 (n = 9) and CCND1 (n = 6). Concordant pathogenic classifications (i.e., pathogenic, benign, or variant of unknown significance) between in-house specialists and WfG included 705 mutations (89.8%; 95% CI, 87.5%-91.8%), 39 amplifications (97.5%; 95% CI, 86.8-99.9%), and 17 fusions (77.3%; 95% CI, 54.6-92.2%). After about 12 months, reanalysis using a more recent version of WfG demonstrated a better concordance rate of 94.5% (95% CI, 92.7-96.0%) for gene mutations. Across the 249 gene alterations determined to be pathogenic by both methods, including mutations, amplifications, and fusions, WfG covered 84.6% (88 of 104) of all targeted therapies that experts proposed and offered an additional 225 therapeutic options. Conclusions: WfG was able to scour large volumes of data from scientific studies and databases to analyze in-house clinical genome sequencing results and demonstrated the potential for application to clinical practice; however, we must train WfG in clinical trial settings.
| S-EPMC6237914 | biostudies-literature
Project description:BackgroundAdvanced stages of different renal diseases feature glomerular sclerosis at a histological level which is observed by light microscopy on tissue samples obtained by performing a kidney biopsy. Computer-aided diagnosis (CAD) systems leverage the potential of artificial intelligence (AI) in healthcare to support physicians in the diagnostic process.MethodsWe propose a novel CAD system that processes histological images and discriminates between sclerotic and non-sclerotic glomeruli. To this goal, we designed, tested, and compared two artificial neural network (ANN) classifiers. The former implements a shallow ANN classifying hand-crafted features extracted from Regions of Interest (ROIs) by means of image-processing procedures. The latter, instead, employs the IBM Watson Visual Recognition System, which uses a deep artificial neural network making decisions taking the images as input, without the need to design any procedure for describing images with features. The input dataset consisted of 428 sclerotic glomeruli and 2344 non-sclerotic glomeruli derived from images of kidney biopsies scanned by the Aperio ScanScope System.ResultsBoth AI approaches allowed to very accurately distinguish (mean MCC 0.95 and mean Accuracy 0.99) between sclerotic and non-sclerotic glomeruli. Although the systems may seem interchangeable, the approach based on feature extraction and classification would allow clinicians to gain information on the most discriminating features. In fact, further procedures could explain the classifier's decision by analysing which subset of features impacted the most on the final decision.ConclusionsWe developed a customizable support system that can facilitate the work of renal pathologists both in clinical and research settings.
| S-EPMC8765108 | biostudies-literature