Aedes aegypti vector control is of paramount importance owing to the damages induced by the various severe diseases that these insects may transmit, and the increasing risk of important outbreaks of ...these pathologies. Search for new chemicals efficient against Aedes aegypti, and devoid of side‐effects, which have been associated to the currently most used active substance i. e. N,N‐diethyl‐m‐toluamide (DEET), is therefore an important issue. In this context, we developed various Quantitative Structure Activity Relationship (QSAR) models to predict the repellent activity against Aedes aegypti of 43 carboxamides, by using Multiple Linear Regression (MLR) and various machine learning approaches. The easy computation of the four topological descriptors selected in this study, compared to the CODESSA descriptors used in the literature, and the predictive ability of the here proposed MLR and machine learning models developed using the software QSARINS and R, make the here proposed QSARs attractive. As demonstrated in this study, these models can be applied at the screening level, to guide the design of new alternatives to DEET.
Use of protective clothing is a simple and efficient way to reduce the contacts with mosquitoes and consequently the probability of transmission of diseases spread by them. This mechanical barrier ...can be enhanced by the application of repellents. Unfortunately the number of available repellents is limited. As a result, there is a crucial need to find new active and safer molecules repelling mosquitoes. In this context, a structure-activity relationship (SAR) model was proposed for the design of repellents active on clothing. It was computed from a dataset of 2027 chemicals for which repellent activity on clothing was measured against Aedes aegypti. Molecules were described by means of 20 molecular descriptors encoding physicochemical properties, topological information and structural features. A three-layer perceptron was used as statistical tool. An accuracy of 87% was obtained for both the training and test sets. Most of the wrong predictions can be explained. Avenues for increasing the performances of the model have been proposed.
The understanding of the mechanisms and interactions that occur when nanomaterials enter biological systems is important to improve their future use. The adsorption of proteins from biological fluids ...in a physiological environment to form a corona on the surface of nanoparticles represents a key step that influences nanoparticle behaviour. In this study, the quantitative description of the composition of the protein corona was used to study the effect on cell association induced by 84 surface-modified gold nanoparticles of different sizes. Quantitative relationships between the protein corona and the activity of the gold nanoparticles were modelled by using several machine learning-based linear and non-linear approaches. Models based on a selection of only six serum proteins had robust and predictive results. The Projection Pursuit Regression method had the best performances (r
2
= 0.91; Q
2
loo = 0.81; r
2
ext = 0.79). The present study confirmed the utility of protein corona composition to predict the bioactivity of gold nanoparticles and identified the main proteins that act as promoters or inhibitors of cell association. In addition, the comparison of several techniques showed which strategies offer the best results in prediction and could be used to support new toxicological studies on gold-based nanomaterials.
Titanium oxide (TiO
2
) and zinc oxide (ZnO) nanoparticles are among the most widely used in different applications in daily life. In this study, local regression and classification models were ...developed for a set of ZnO and TiO
2
nanoparticles tested at different concentrations for their ability to disrupt the lipid membrane in cells. Different regression techniques were applied and compared by checking the robustness of the models and their external predictive ability. Additionally, a simple classification model was developed, which predicts the potential for disruption of the studied nanoparticles with good accuracy (overall accuracy, specificity, and sensitivity >80%) on the basis of two empirical descriptors. The present study demonstrates that empirical descriptors, such as experimentally determined size and tested concentrations, are relevant to modelling the activity of nanoparticles. This information may be useful to screen the potential for harmful effect of nanoparticles in different experimental conditions and to optimize the design of toxicological tests. Results from the present study are useful to support and refine the future application of in silico tools to nanoparticles, for research and regulatory purposes.
QSAR models are proposed for predicting the toxicity of 33 piperidine derivatives against Aedes aegypti. From 2D topological descriptors, calculated with the PaDEL software, ordinary least squares ...multilinear regression (OLS-MLR) treatment from the QSARINS software and machine learning and related approaches including linear and radial support vector machine (SVM), projection pursuit regression (PPR), radial basis function neural network (RBFNN), general regression neural network (GRNN) and k-nearest neighbours (k-NN), led to four-variable models. Their robustness and predictive ability were evaluated through both internal and external validation. Determination coefficients (r
2
) greater than 0.85 on the training sets and 0.8 on the test sets were obtained with OLS-MLR and linear SVM. They slightly outperform PPR, radial SVM and RBFNN, whereas GRNN and k-NN showed lower performance. The easy availability of the involved structural descriptors and the simplicity of the MLR model make the corresponding model attractive at an exploratory level for proposing, from this limited dataset, guidelines in the design of new potentially active molecules.
The use of functionalized nanomaterials is of high importance in biomedical applications like the efficient targeting of cancer cells. This paper proposes a comparison of different statistical and ...mechanistic aspects of new QSAR models generated to predict the selective uptake of a library of surface modified nanoparticles tested in different human cell types. Additionally, a new approach based on the combination of multivariate factorial analysis and QSAR is proposed to generate a 2-dimensional map of the selective uptake of the surface modified nanoparticles into multiple cell types. This map offers an immediate view of the uptake of the nanoparticles, distinguishing among those with high or low uptake in one or more of the studied cells. Finally, QSAR models are generated to predict the coordinates of the studied nanoparticles in the 2D map from their molecular structure. This predictive map is useful to screen new and existing surface modified nanoparticles for diagnostic and biomedical uses.
Support vector machines (SVMs) were used to develop QSAR models that correlate molecular structures to their toxicity and bioactivities. The performance and predictive ability of SVM are investigated ...and compared with other methods such as multiple linear regression and radial basis function neural network methods. In the present study, two different data sets were evaluated. The first one involves an application of SVM to the development of a QSAR model for the prediction of toxicities of 153 phenols, and the second investigation deals with the QSAR model between the structures and the activities of a set of 85 cyclooxygenase 2 (COX-2) inhibitors. For each application, the molecular structures were described using either the physicochemical parameters or molecular descriptors. In both studied cases, the predictive ability of the SVM model is comparable or superior to those obtained by MLR and RBFNN. The results indicate that SVM can be used as an alternative powerful modeling tool for QSAR studies.
An attempt was made to derive structure-activity models allowing the prediction of the larvicidal activity of structurally diverse chemicals against mosquitoes. A database of 188 chemicals with their ...activity on Aedes aegypti larvae was constituted from analysis of original publications. The activity values were expressed in log 1/IC
50
(concentration required to produce 50% inhibition of larval development, mmol). All the chemicals were encoded by means of CODESSA and autocorrelation descriptors. Partial least squares analysis, classification and regression tree, random forest and boosting regression tree analyses, Kohonen self-organizing maps, linear artificial neural networks, three-layer perceptrons, radial basis function artificial neural networks and support vector machines with linear, polynomial, radial basis function and sigmoid kernels were tested as statistical tools. Because quantitative models did not give good results, a two-class model was designed. The three-layer perceptron significantly outperformed the other statistical approaches regardless of the threshold value used to split the data into active and inactive compounds. The most interesting configuration included eight autocorrelation descriptors as input neurons and four neurons in the hidden layer. This led to more than 96% of good predictions on both the training set and external test set of 88 and 100 chemicals, respectively. From the overall simulation results, new candidate molecules were proposed which will be shortly synthesized and tested.
Juvenile hormone esterase (JHE) plays a key role in the development and metamorphosis of holometabolous insects. Its inhibitors could possibly be targeted for insect control. Conversely, JHE may also ...be involved in endocrine disruption by xenobiotics, resulting in detrimental effects in beneficial insects. There is therefore a need to know the structural characteristics of the molecules able to monitor JHE activity, and to develop SAR and QSAR studies to estimate their effectiveness. For a large diverse population of 181 trifluoromethylketones (TFKs) - the most potent JHE inhibitors known to date - we recently proposed a binary classification (active/inactive) using a support vector machine and Codessa structural descriptors. We have now examined, using the same data set and with the same descriptors, the applicability and performance of five other machine learning approaches. These have been shown able to handle high dimensional data (with descriptors possibly irrelevant or redundant) and to cope with complex mechanisms, but without delivering explicit directly exploitable models. Splitting the data into five batches (training set 80%, test set 20%) and carrying out leave-one-out cross-validation, led to good results of comparable performance, consistent with our previous support vector classifier (SVC) results. Accuracy was greater than 0.80 for all approaches. A reduced set of 15 descriptors common to all the investigated approaches showed good predictive ability (confirmed using a three-layer perceptron) and gives some clues regarding a mechanistic interpretation.
The juvenile hormone esterase (JHE) regulates juvenile hormone titre in insect hemolymph during its larval development. It has been suggested that JHE could be targeted for use in insect control. ...This enzyme can also be considered as involved in the phenomenon of endocrine disruption by xenobiotics in beneficial insects. Consequently, there is a need to know the characteristics of the molecules able to act on the JHE. Trifluoromethylketones (TFKs) are the most potent JHE inhibitors found to date and different quantitative structure-activity relationships (QSARs) have been derived for this group of chemicals. In this context, a set of 181 TFKs (118 active and 63 inactive compounds), tested on Trichoplusia ni for their JHE inhibition activity and described by physico-chemical descriptors, was split into different training and test sets to derive structure-activity relationship (SAR) models from support vector classification (SVC). A SVC model including 88 descriptors and derived from a Gaussian kernel was selected for its predictive performances. Another model computed only with 13 descriptors was also selected due to its mechanistic interpretability. This study clearly illustrates the difficulty in capturing the essential structural characteristics of the TFKs explaining their JHE inhibitory activity.
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