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Diffstat (limited to 'loael.Rmd')
| -rw-r--r-- | loael.Rmd | 63 |
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@@ -1,15 +1,27 @@ --- -author: | - Christoph Helma^1^, David Vorgrimmler^1^, Denis Gebele^1^, Martin Gütlein^2^, Benoit Schilter^3^, Elena Lo Piparo^3^ -title: | - Modeling Chronic Toxicity: A comparison of experimental variability with read across predictions +title: 'Modeling Chronic Toxicity: A comparison of experimental variability with read across predictions' +author: + - Christoph Helma^1^ + - David Vorgrimmler^1^ + - Denis Gebele^1^ + - Martin Gütlein^2^ + - Benoit Schilter^3^ + - Elena Lo Piparo^3^ include-before: ^1^ in silico toxicology gmbh, Basel, Switzerland\newline^2^ Inst. f. Computer Science, Johannes Gutenberg Universität Mainz, Germany\newline^3^ Chemical Food Safety Group, Nestlé Research Center, Lausanne, Switzerland -keywords: (Q)SAR, read-across, LOAEL +keywords: (Q)SAR, read-across, LOAEL, experimental variability date: \today -abstract: " " -documentclass: achemso +abstract: | + This study compares the accuracy of (Q)SAR/read-across predictions with the + experimental variability of chronic LOAEL values from *in vivo* experiments. + We could demonstrate that predictions of the `lazar` lazar algrorithm within + the applicability domain of the training data have the same variability as + the experimental training data. Predictions with a lower similarity threshold + (i.e. a larger distance from the applicability domain) are also significantly + better than random guessing, but the errors to be expected are higher and + a manual inspection of prediction results is highly recommended. + +documentclass: article bibliography: references.bibtex -bibliographystyle: achemso figPrefix: Figure eqnPrefix: Equation tblPrefix: Table @@ -18,6 +30,8 @@ output: pdf_document: fig_caption: yes header-includes: + - \usepackage{a4wide} + - \linespread{2} - \usepackage{lineno} - \linenumbers ... @@ -89,12 +103,20 @@ were exploited to generate information on the reproducibility of chronic animal studies and were used to evaluate prediction performance of the models in the context of experimental variability. -An important limitation often raised for computational toxicology is the -lack of transparency on published models and consequently on the -difficulty for the scientific community to reproduce and apply them. To +An important limitation often raised for computational toxicology is the lack +of transparency on published models and consequently on the difficulty for the +scientific community to reproduce and apply them. To overcome these issues, +source code for all programs and libraries and the databases that have been used to generate this +manuscript are made available under GPL3 licenses. Databases and compiled +programs with all dependencies for the reproduction of results in this manuscript are available as +a self-contained docker image. All data, tables and figures in this manuscript +was generated directly from experimental results using the `R` package `knitR`. +A single command repeats all experiments (possibly with different settings) and +updates the manuscript with the new results. + +<!-- overcome these issues, all databases and programs that have been used to generate this manuscript are made available under GPL3 licenses. - A self-contained docker image with all programs, libraries and data required for the reproduction of these results is available from <https://hub.docker.com/r/insilicotox/loael-paper/>. @@ -109,7 +131,7 @@ A graphical webinterface for `lazar` model predictions and validation results is publicly accessible at <https://lazar.in-silico.ch>, models presented in this manuscript will be included in future versions. Source code for the GUI can be obtained from <https://github.com/opentox/lazar-gui>. - +--> Materials and Methods ===================== @@ -128,9 +150,11 @@ observed effect levels (LOAEL) for rats (*Rattus norvegicus*) after oral (gavage, diet, drinking water) administration. The Nestlé database consists of `r length(m$SMILES)` LOAEL values for `r length(unique(m$SMILES))` unique chemical structures. -The Nestlé database can be obtained from the following GitHub links: [original data](https://github.com/opentox/loael-paper/blob/submission/data/LOAEL_mg_corrected_smiles_mmol.csv), -[unique smiles](https://github.com/opentox/loael-paper/blob/submission/data/mazzatorta.csv), -[-log10 transfomed LOAEL](https://github.com/opentox/loael-paper/blob/submission/data/mazzatorta_log10.csv). +The Nestlé database can be obtained from the following GitHub links: + + - original data: [https://github.com/opentox/loael-paper/blob/submission/data/LOAEL_mg_corrected_smiles_mmol.csv](https://github.com/opentox/loael-paper/blob/submission/data/LOAEL_mg_corrected_smiles_mmol.csv) + - unique smiles: [https://github.com/opentox/loael-paper/blob/submission/data/mazzatorta.csv](https://github.com/opentox/loael-paper/blob/submission/data/mazzatorta.csv) + - -log10 transfomed LOAEL: [https://github.com/opentox/loael-paper/blob/submission/data/mazzatorta_log10.csv](https://github.com/opentox/loael-paper/blob/submission/data/mazzatorta_log10.csv). ### Swiss Food Safety and Veterinary Office (FSVO) database @@ -143,9 +167,10 @@ described elsewhere [@Zarn2011, @Zarn2013]. The FSVO-database consists of `r length(s$SMILES)` rat LOAEL values for `r length(unique(s$SMILES))` unique chemical structures. It can be obtained from the following GitHub links: -[original data](https://github.com/opentox/loael-paper/blob/submission/data/NOAEL-LOAEL_SMILES_rat_chron.csv), -[unique smiles and mmol/kg_bw/day units](https://github.com/opentox/loael-paper/blob/submission/data/swiss.csv), -[-log10 transfomed LOAEL](https://github.com/opentox/loael-paper/blob/submission/data/swiss_log10.csv). + - original data: [https://github.com/opentox/loael-paper/blob/submission/data/NOAEL-LOAEL_SMILES_rat_chron.csv](https://github.com/opentox/loael-paper/blob/submission/data/NOAEL-LOAEL_SMILES_rat_chron.csv) + - unique smiles and mmol/kg_bw/day units: [https://github.com/opentox/loael-paper/blob/submission/data/swiss.csv](https://github.com/opentox/loael-paper/blob/submission/data/swiss.csv) + - -log10 transfomed LOAEL: [https://github.com/opentox/loael-paper/blob/submission/data/swiss_log10.csv](https://github.com/opentox/loael-paper/blob/submission/data/swiss_log10.csv) + ### Preprocessing |