| 1. |
- Ahmed, Laeeq, et al.
(författare)
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Predicting target profiles with confidence as a service using docking scores
- 2020
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Ingår i: Journal of Cheminformatics. - : Springer Nature. - 1758-2946. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying and assessing ligand-target binding is a core component in early drug discovery as one or more unwanted interactions may be associated with safety issues. Contributions: We present an open-source, extendable web service for predicting target profiles with confidence using machine learning for a panel of 7 targets, where models are trained on molecular docking scores from a large virtual library. The method uses conformal prediction to produce valid measures of prediction efficiency for a particular confidence level. The service also offers the possibility to dock chemical structures to the panel of targets with QuickVina on individual compound basis. Results: The docking procedure and resulting models were validated by docking well-known inhibitors for each of the 7 targets using QuickVina. The model predictions showed comparable performance to molecular docking scores against an external validation set. The implementation as publicly available microservices on Kubernetes ensures resilience, scalability, and extensibility.
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| 2. |
- Heggenes, Jan, et al.
(författare)
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Herbivore grazing—or trampling? Trampling effects by a large ungulate in cold high-latitude ecosystems
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:16, s. 6423-6431
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian herbivores have important top-down effects on ecological processes and landscapes by generating vegetation changes through grazing and trampling. For free-ranging herbivores on large landscapes, trampling is an important ecological factor. However, whereas grazing is widely studied, low-intensity trampling is rarely studied and quantified. The cold-adapted northern tundra reindeer (Rangifer tarandus) is a wide-ranging keystone herbivore in large open alpine and Arctic ecosystems. Reindeer may largely subsist on different species of slow-growing ground lichens, particularly in winter. Lichen grows in dry, snow-poor habitats with frost. Their varying elasticity makes them suitable for studying trampling. In replicated factorial experiments, high-resolution 3D laser scanning was used to quantify lichen volume loss from trampling by a reindeer hoof. Losses were substantial, that is, about 0.3 dm3 per imprint in dry thick lichen, but depended on type of lichen mat and humidity. Immediate trampling volume loss was about twice as high in dry, compared to humid thin (2–3 cm), lichen mats and about three times as high in dry vs. humid thick (6–8 cm) lichen mats, There was no significant difference in volume loss between 100% and 50% wetted lichen. Regained volume with time was insignificant for dry lichen, whereas 50% humid lichen regained substantial volumes, and 100% humid lichen regained almost all lost volume, and mostly within 10–20 min. Reindeer trampling may have from near none to devastating effects on exposed lichen forage. During a normal week of foraging, daily moving 5 km across dry 6- to 8-cm-thick continuous lichen mats, one adult reindeer may trample a lichen volume corresponding to about a year's supply of lichen. However, the lichen humidity appears to be an important factor for trampling loss, in addition to the extent of reindeer movement.
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| 3. |
- Idoia Biurrun, Idoia, et al.
(författare)
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GrassPlot v. 2.00 – first update on the database of multi-scale plant diversity in Palaearctic grasslands
- 2019
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Ingår i: Palaearctic Grasslands. - : Eurasian Dry Grassland Group (EDGG). - 2627-9827. ; :44, s. 26-47
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Tidskriftsartikel (refereegranskat)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). Following a previous Long Database Report (Dengler et al. 2018, Phytocoenologia 48, 331–347), we provide here the first update on content and functionality of GrassPlot. The current version (GrassPlot v. 2.00) contains a total of 190,673 plots of different grain sizes across 28,171 independent plots, with 4,654 nested-plot series including at least four grain sizes. The database has improved its content as well as its functionality, including addition and harmonization of header data (land use, information on nestedness, structure and ecology) and preparation of species composition data. Currently, GrassPlot data are intensively used for broad-scale analyses of different aspects of alpha and beta diversity in grassland ecosystems.
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| 4. |
- Lampa, Samuel, et al.
(författare)
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Predicting off-target binding profiles with confidence using Conformal Prediction
- 2018
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Ligand-based models can be used in drug discovery to obtain an early indication of potential off-target interactions that could be linked to adverse effects. Another application is to combine such models into a panel, allowing to compare and search for compounds with similar profiles. Most contemporary methods and implementations however lack valid measures of confidence in their predictions, and only providing point predictions. We here describe the use of conformal prediction for predicting off-target interactions with models trained on data from 31 targets in the ExCAPE dataset, selected for their utility in broad early hazard assessment. Chemicals were represented by the signature molecular descriptor and support vector machines were used as the underlying machine learning method. By using conformal prediction, the results from predictions come in the form of confidence p-values for each class. The full pre-processing and model training process is openly available as scientific workflows on GitHub, rendering it fully reproducible. We illustrate the usefulness of the methodology on a set of compounds extracted from DrugBank. The resulting models are published online and are available via a graphical web interface and an OpenAPI interface for programmatic access.
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| 5. |
- Lapins, Maris, et al.
(författare)
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A confidence predictor for logD using conformal regression and a support-vector machine
- 2018
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Ingår i: Journal of Cheminformatics. - : Springer Science and Business Media LLC. - 1758-2946. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Lipophilicity is a major determinant of ADMET properties and overall suitability of drug candidates. We have developed large-scale models to predict water-octanol distribution coefficient (logD) for chemical compounds, aiding drug discovery projects. Using ACD/logD data for 1.6 million compounds from the ChEMBL database, models are created and evaluated by a support-vector machine with a linear kernel using conformal prediction methodology, outputting prediction intervals at a specified confidence level. The resulting model shows a predictive ability of [Formula: see text] and with the best performing nonconformity measure having median prediction interval of [Formula: see text] log units at 80% confidence and [Formula: see text] log units at 90% confidence. The model is available as an online service via an OpenAPI interface, a web page with a molecular editor, and we also publish predictive values at 90% confidence level for 91 M PubChem structures in RDF format for download and as an URI resolver service.
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| 6. |
- Spjuth, Ola, 1977-, et al.
(författare)
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Applications of the InChI in cheminformatics with the CDK and Bioclipse
- 2013
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Ingår i: Journal of Cheminformatics. - : Springer Science and Business Media LLC. - 1758-2946. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe InChI algorithms are written in C++ and not available as Java library. Integration into softwarewritten in Java therefore requires a bridge between C and Java libraries, provided by the Java NativeInterface (JNI) technology.ResultsWe here describe how the InChI library is used in the Bioclipse workbench and the Chemistry Development Kit (CDK) cheminformatics library. To make this possible, a JNI bridge to the InChIlibrary was developed, JNI-InChI, allowing Java software to access the InChI algorithms. By usingthis bridge, the CDK project packages the InChI binaries in a module and offers easy access fromJava using the CDK API. The Bioclipse project packages and offers InChI as a dynamic OSGi bundlethat can easily be used by any OSGi-compliant software, in addition to the regular Java Archive andMaven bundles. Bioclipse itself uses the InChI as a key component and calculates it on the fly whenvisualizing and editing chemical structures. We demonstrate the utility of InChI with various applications in CDK and Bioclipse, such as decision support for chemical liability assessment, tautomergeneration, and for knowledge aggregation using a linked data approach.ConclusionsThese results show that the InChI library can be used in a variety of Java library dependency solutions, making the functionality easily accessible by Java software, such as in the CDK. The applications show various ways the InChI has been used in Bioclipse, to enrich its functionality.
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| 7. |
- Spjuth, Ola, 1977-, et al.
(författare)
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Bioclipse 2: A scriptable integration platform for the life sciences
- 2009
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 10, s. 397-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Contemporary biological research integrates neighboring scientific domains to answer complex ques- tions in fields such as systems biology and drug discovery. This calls for tools that are intuitive to use, yet flexible to adapt to new tasks. Results: Bioclipse is a free, open source workbench with advanced features for the life sciences. Version 2.0 constitutes a complete rewrite of Bioclipse, and delivers a stable, scalable integration platform for developers and an intuitive workbench for end users. All functionality is available both from the graphical user interface and from a built-in novel domain-specific language, supporting the scientist in interdisciplinary research and reproducible analyses through advanced visualization of the inputs and the results. New components for Bioclipse 2 include a rewritten editor for chemical structures, a table for multiple molecules that supports gigabyte-sized files, as well as a graphical editor for sequences and alignments. Conclusions: Bioclipse 2 is equipped with advanced tools required to carry out complex analysis in the fields of bio- and cheminformatics. Developed as a Rich Client based on Eclipse, Bioclipse 2 leverages on today’s powerful desktop computers for providing a responsive user interface, but also takes full advantage of the Web and networked (Web/Cloud) services for more demanding calculations or retrieval of data. That Bioclipse 2 is based on an advanced and widely used service platform ensures wide extensibility, and new algorithms, visualizations as well as scripting commands can easily be added. The intuitive tools for end users and the extensible architecture make Bioclipse 2 ideal for interdisciplinary and integrative research. Bioclipse 2 is released under the Eclipse Public License (EPL), a flexible open source license that allows additional plugins to be of any license. Bioclipse 2 is implemented in Java and supported on all major platforms; Source code and binaries are freely available at http://www.bioclipse.net.
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| 8. |
- Spjuth, Ola, 1977-, et al.
(författare)
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Bioclipse-R : Integrating management and visualization of life science data with statistical analysis
- 2013
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Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811. ; 29:2, s. 286-289
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Tidskriftsartikel (refereegranskat)abstract
- Bioclipse, a graphical workbench for the life sciences, provides functionality for managing and visualizing life science data. We introduce Bioclipse-R, which integrates Bioclipse and the statistical programming language R. The synergy between Bioclipse and R is demonstrated by the construction of a decision support system for anticancer drug screening and mutagenicity prediction, which shows how Bioclipse-R can be used to perform complex tasks from within a single software system.
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| 9. |
- Willighagen, Egon L., et al.
(författare)
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The Chemistry Development Kit (CDK) v2.0 : atom typing, depiction, molecular formulas, and substructure searching
- 2017
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Ingår i: Journal of Cheminformatics. - : Springer Science and Business Media LLC. - 1758-2946. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Chemistry Development Kit (CDK) is a widely used open source cheminformatics toolkit, providing data structures to represent chemical concepts along with methods to manipulate such structures and perform computations on them. The library implements a wide variety of cheminformatics algorithms ranging from chemical structure canonicalization to molecular descriptor calculations and pharmacophore perception. It is used in drug discovery, metabolomics, and toxicology. Over the last 10 years, the code base has grown significantly, however, resulting in many complex interdependencies among components and poor performance of many algorithms.Results: We report improvements to the CDK v2.0 since the v1.2 release series, specifically addressing the increased functional complexity and poor performance. We first summarize the addition of new functionality, such atom typing and molecular formula handling, and improvement to existing functionality that has led to significantly better performance for substructure searching, molecular fingerprints, and rendering of molecules. Second, we outline how the CDK has evolved with respect to quality control and the approaches we have adopted to ensure stability, including a code review mechanism.Conclusions: This paper highlights our continued efforts to provide a community driven, open source cheminformatics library, and shows that such collaborative projects can thrive over extended periods of time, resulting in a high-quality and performant library. By taking advantage of community support and contributions, we show that an open source cheminformatics project can act as a peer reviewed publishing platform for scientific computing software.
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