Consensus QSAR Related to Global or MOA Models: Application to Acute Toxicity for Fish

Lozano, Sylvain; Halm-Lemeille, Marie-Pierre; Lepailleur, Alban; Rault, Syl­vain; Bureau, Ronan

doi:10.1002/minf.201000104

Cited by 12 publications

(13 citation statements)

References 35 publications

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“…Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants and young children [ 1 , 2 , 3 ], responsible for one-third of deaths resulting from acute lower respiratory infection in the first year of life [ 4 , 5 , 6 ]. RSV also causes severe respiratory tract disease in immunosuppressed and older adults, leading to substantial annual mortality [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Requirements for Self-Interaction of the Respiratory Syncytial Virus Matrix Protein in Living Mammalian Cells

Trevisan

Antonio

Radeghieri

et al. 2018

Viruses

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Respiratory syncytial virus (RSV) is an important human pathogen, which infects respiratory tract epithelial cells causing bronchiolitis and pneumonia in children and the elderly. Recent studies have linked RSV matrix (M) ability to self-interaction and viral budding. However, RSV M has been crystalized both as a monomer and a dimer, and no formal proof exists to date that it forms dimers in cells. Here, by using a combination of confocal laser scanning microscopy and bioluminescent resonant energy transfer applied to differently tagged deletion mutants of RSV M, we show that the protein can self-interact in living mammalian cells and that both the N and C-terminus of the protein are strictly required for the process, consistent with the reported dimeric crystal structure.

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Section: Introductionmentioning

confidence: 99%

Molecular Requirements for Self-Interaction of the Respiratory Syncytial Virus Matrix Protein in Living Mammalian Cells

Trevisan

Antonio

Radeghieri

et al. 2018

Viruses

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“…The application domain was further analyzed by evaluating large differences (>1.5 log unit ) between predicted and observed values for chemicals in the test set. For nonpolar narcosis, 3 substances (4 data points) out of the 50 used in the training set resulted in higher toxicity than predicted.…”

Section: Resultsmentioning

confidence: 99%

Development and validation of a quantitative structure–activity relationship for chronic narcosis to fish

Claeys¹,

Iaccino²,

Janssen

et al. 2013

Enviro Toxic and Chemistry

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Vertebrate testing under the European Union's regulation on Registration, Evaluation, Authorisation and Restriction of Chemical substances (REACH) is discouraged, and the use of alternative nontesting approaches such as quantitative structure-activity relationships (QSARs) is encouraged. However, robust QSARs predicting chronic ecotoxicity of organic compounds to fish are not available. The Ecological Structure Activity Relationships (ECOSAR) Class Program is a computerized predictive system that estimates the acute and chronic toxicity of organic compounds for several chemical classes based on their log octanol-water partition coefficient (K OW ). For those chemical classes for which chronic training data sets are lacking, acute to chronic ratios are used to predict chronic toxicity to aquatic organisms. Although ECOSAR reaches a high score against the Organisation for Economic Co-operation and Development (OECD) principles for QSAR validation, the chronic QSARs in ECOSAR are not fully compliant with OECD criteria in the framework of REACH or CLP (classification, labeling, and packaging) regulation. The objective of the present study was to develop a chronic ecotoxicity QSAR for fish for compounds acting via nonpolar and polar narcosis. These QSARs were built using a database of quality screened toxicity values, considering only chronic exposure durations and relevant end points. After statistical multivariate diagnostic analysis, literature-based, mechanistically relevant descriptors were selected to develop a multivariate regression model. Finally, these QSARs were tested for their acceptance for regulatory purposes and were found to be compliant with the OECD principles for the validation of a QSAR.

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“…The assumption is that the strengths of one model will counterbalance the weaknesses of the others and vice versa. Previous studies have already shown the beneficial effects of consensus modelling when dealing with ecotoxicological endpoints [39][40][41][42].…”

Section: Consensus Modellingmentioning

confidence: 97%

Validation and extension of a similarity-based approach for prediction of acute aquatic toxicity towards Daphnia magna

Cassotti

Consonni

Mauri

et al. 2014

SAR and QSAR in Environmental Research

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Quantitative structure-activity relationship (QSAR) models for predicting acute toxicity to Daphnia magna are often associated with poor performances, urging the need for improvement to meet REACH requirements. The aim of this study was to evaluate the accuracy, stability and reliability of a previously published QSAR model by means of further external validation and to optimize its performance by means of extension to new data as well as a consensus approach. The previously published model was validated with a large set of new molecules and then compared with ChemProp model, from which most of the validation data were taken. Results showed better performance of the proposed model in terms of accuracy and percentage of molecules outside the applicability domain. The model was re-calibrated on all the available data to confirm the efficacy of the similarity-based approach. The extended dataset was also used to develop a novel model based on the same similarity approach but using binary fingerprints to describe the chemical structures. The fingerprint-based model gave lower regression statistics, but also less unpredicted compounds. Eventually, consensus modelling was successfully used to enhance the accuracy of the predictions and to halve the percentage of molecules outside the applicability domain.

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Consensus QSAR Related to Global or MOA Models: Application to Acute Toxicity for Fish

Cited by 12 publications

References 35 publications

Molecular Requirements for Self-Interaction of the Respiratory Syncytial Virus Matrix Protein in Living Mammalian Cells

Molecular Requirements for Self-Interaction of the Respiratory Syncytial Virus Matrix Protein in Living Mammalian Cells

Development and validation of a quantitative structure–activity relationship for chronic narcosis to fish

Validation and extension of a similarity-based approach for prediction of acute aquatic toxicity towards Daphnia magna

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