Dataset Information

Using human in vitro transcriptome analysis to build trustworthy machine learning models for prediction of animal drug toxicity.

ABSTRACT: During the development of new drugs or compounds there is a requirement for preclinical trials, commonly involving animal tests, to ascertain the safety of the compound prior to human trials. Machine learning techniques could provide an in-silico alternative to animal models for assessing drug toxicity, thus reducing expensive and invasive animal testing during clinical trials, for drugs that are most likely to fail safety tests. Here we present a machine learning model to predict kidney dysfunction, as a proxy for drug induced renal toxicity, in rats. To achieve this, we use inexpensive transcriptomic profiles derived from human cell lines after chemical compound treatment to train our models combined with compound chemical structure information. Genomics data due to its sparse, high-dimensional and noisy nature presents significant challenges in building trustworthy and transparent machine learning models. Here we address these issues by judiciously building feature sets from heterogenous sources and coupling them with measures of model uncertainty achieved through Gaussian Process based Bayesian models. We combine the use of insight into the feature-wise contributions to our predictions with the use of predictive uncertainties recovered from the Gaussian Process to improve the transparency and trustworthiness of the model.

SUBMITTER: Gardiner LJ

PROVIDER: S-EPMC7293302 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using human in vitro transcriptome analysis to build trustworthy machine learning models for prediction of animal drug toxicity.

Gardiner Laura-Jayne LJ Carrieri Anna Paola AP Wilshaw Jenny J Checkley Stephen S Pyzer-Knapp Edward O EO Krishna Ritesh R

Scientific reports 20200612 1

During the development of new drugs or compounds there is a requirement for preclinical trials, commonly involving animal tests, to ascertain the safety of the compound prior to human trials. Machine learning techniques could provide an in-silico alternative to animal models for assessing drug toxicity, thus reducing expensive and invasive animal testing during clinical trials, for drugs that are most likely to fail safety tests. Here we present a machine learning model to predict kidney dysfunc ...[more]

PMID: 32533004

Similar Datasets

Project description:Different types of chemicals and products may exhibit various health risks when administered into the human body. For toxicity reasons, the number of new drugs entering the market through the conventional drug development process has been reduced over the years. However, with the advent of big data and artificial intelligence, machine learning techniques have emerged as a potential solution for predicting toxicity and ensuring efficient drug development and chemical safety. An ML model for toxicity prediction can reduce experimental costs and time while addressing ethical concerns by drastically reducing the need for animals and clinical trials. Herein, MolToxPred, an ML-based tool, has been developed using a stacked model approach to predict the potential toxicity of small molecules and metabolites. The stacked model consists of random forest, multi-layer perceptron, and LightGBM as base classifiers and Logistic Regression as the meta classifier. For training and validation purposes, a comprehensive set of toxic and non-toxic molecules is curated. Different structural and physicochemical-based features in the form of molecular descriptors and fingerprints were employed. MolToxPred utilizes a comprehensive feature selection process and optimizes its hyperparameters through Bayesian optimization with stratified 5-fold cross-validation. In the evaluation phase, MolToxPred achieved an AUROC of 87.76% on the test set and 88.84% on an external validation set. The McNemar test was used as the post-hoc test to determine if the stacked models' performance was significantly different compared to the base learners. The developed stacked model outperformed its base classifiers and an existing tool in the literature, reaffirming its better performance. The hypothesis is that the incorporation of a diverse set of data, the subsequent feature selection, and a stacked ensemble approach give MolToxPred the edge over other methods. In addition to this, an attempt has been made to identify structural alerts responsible for endpoints of the Tox21 data to determine the association of a molecule with a plausible downstream pathway of action. MolToxPred may be helpful for drug discovery and regulatory pipelines in pharmaceutical and other industries for in silico toxicity prediction of small molecule candidates.

Project description:Nitrogen is the most limiting nutrient for turfgrass growth. Instead of pursuing the maximum yield, most turfgrass managers use nitrogen (N) to maintain a sub-maximal growth rate. Few tools or soil tests exist to help managers guide N fertilizer decisions. Turf growth prediction models have the potential to be useful, but the currently existing turf growth prediction model only takes temperature into account, limiting its accuracy. This study developed machine-learning-based turf growth models using the random forest (RF) algorithm to estimate short-term turfgrass clipping yield. To build the RF model, a large set of variables were extracted as predictors including the 7-day weather, traffic intensity, soil moisture content, N fertilization rate, and the normalized difference red edge (NDRE) vegetation index. In this study, the data were collected from two putting greens where the turfgrass received 0 to 1,800 round/week traffic rates, various irrigation rates to maintain the soil moisture content between 9 and 29%, and N fertilization rates of 0 to 17.5 kg ha-1 applied biweekly. The RF model agreed with the actual clipping yield collected from the experimental results. The temperature and relative humidity were the most important weather factors. Including NDRE improved the prediction accuracy of the model. The highest coefficient of determination (R2) of the RF model was 0.64 for the training dataset and was 0.47 for the testing data set upon the evaluation of the model. This represented a large improvement over the existing growth prediction model (R 2 = 0.01). However, the machine-learning models created were not able to accurately predict the clipping production at other locations. Individual golf courses can create customized growth prediction models using clipping volume to eliminate the deviation caused by temporal and spatial variability. Overall, this study demonstrated the feasibility of creating machine-learning-based yield prediction models that may be able to guide N fertilization decisions on golf course putting greens and presumably other turfgrass areas.

Project description:BackgroundAccurate and reliable predictions of infectious disease can be valuable to public health organizations that plan interventions to decrease or prevent disease transmission. A great variety of models have been developed for this task. However, for different data series, the performance of these models varies. Hepatitis E, as an acute liver disease, has been a major public health problem. Which model is more appropriate for predicting the incidence of hepatitis E? In this paper, three different methods are used and the performance of the three methods is compared.MethodsAutoregressive integrated moving average(ARIMA), support vector machine(SVM) and long short-term memory(LSTM) recurrent neural network were adopted and compared. ARIMA was implemented by python with the help of statsmodels. SVM was accomplished by matlab with libSVM library. LSTM was designed by ourselves with Keras, a deep learning library. To tackle the problem of overfitting caused by limited training samples, we adopted dropout and regularization strategies in our LSTM model. Experimental data were obtained from the monthly incidence and cases number of hepatitis E from January 2005 to December 2017 in Shandong province, China. We selected data from July 2015 to December 2017 to validate the models, and the rest was taken as training set. Three metrics were applied to compare the performance of models, including root mean square error(RMSE), mean absolute percentage error(MAPE) and mean absolute error(MAE).ResultsBy analyzing data, we took ARIMA(1, 1, 1), ARIMA(3, 1, 2) as monthly incidence prediction model and cases number prediction model, respectively. Cross-validation and grid search were used to optimize parameters of SVM. Penalty coefficient C and kernel function parameter g were set 8, 0.125 for incidence prediction, and 22, 0.01 for cases number prediction. LSTM has 4 nodes. Dropout and L2 regularization parameters were set 0.15, 0.001, respectively. By the metrics of RMSE, we obtained 0.022, 0.0204, 0.01 for incidence prediction, using ARIMA, SVM and LSTM. And we obtained 22.25, 20.0368, 11.75 for cases number prediction, using three models. For MAPE metrics, the results were 23.5%, 21.7%, 15.08%, and 23.6%, 21.44%, 13.6%, for incidence prediction and cases number prediction, respectively. For MAE metrics, the results were 0.018, 0.0167, 0.011 and 18.003, 16.5815, 9.984, for incidence prediction and cases number prediction, respectively.ConclusionsComparing ARIMA, SVM and LSTM, we found that nonlinear models(SVM, LSTM) outperform linear models(ARIMA). LSTM obtained the best performance in all three metrics of RSME, MAPE, MAE. Hence, LSTM is the most suitable for predicting hepatitis E monthly incidence and cases number.

Dataset Information

Using human in vitro transcriptome analysis to build trustworthy machine learning models for prediction of animal drug toxicity.

Publications

Using human in vitro transcriptome analysis to build trustworthy machine learning models for prediction of animal drug toxicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets