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Toxics
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Predictive Toxicology
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Predictive Toxicology

A topical collection in Toxics (ISSN 2305-6304). This collection belongs to the section "Novel Methods in Toxicology Research".

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Editor

Dr. Minjun Chen

E-Mail Website
Collection Editor
National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079, USA
Interests: bioinformatics; drug-induced liver injury; drug safety; biomarker discovery; toxicogenomics
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

The recent advances of toxicogenomics, high-throughput screening, stem cells, and image analysis are creating unique opportunities to improve our ability to predict risk in humans and the development of predictive toxicology. These modern biotechnologies are producing big toxicological data and require advanced artificial intelligence technologies to evaluate the potential for predicting toxicity. The application of conventional machine learning algorithms, such as logical regression, decision tree, and support vector machines, have largely enhanced our capability to recover useful knowledge from the increasing volume of toxicity data. A recent study reported by researchers from John Hopkins University, demonstrated that using artificial intelligent algorithms trained on chemical-safety, big data could be more predictive and outperform expensive animals studies on some toxicities. Notably, the development of deep learning techniques, with the help of advanced computer technologies (e.g., the use of graphical processing units (GPU)) and complicated neural network algorithms, have brought about breakthroughs in computer vision and pattern recognition, image and speech recognition, drug discovery, and toxicology. In several public scientific challenges, including the Merck-sponsored Kaggle competition in 2012 and the Tox21 Data Challenge in 2015, deep learning algorithms demonstrated a superior predictive performance to convenient machine learning algorithms.

In this Topical Collection, we focus on exploring the relationship between the toxicity of xenobiotics and their chemical structures, disturbed cellular, and molecular pathways by the application of artificial intelligent methods to improve the prediction of toxicity risk. In addition, we especially encourage submissions on applying deep learning techniques to process datasets from high-dimensional gene expression, image and high-throughput screening, and chemical structures.

You may choose our Joint Topical Collection in IJERPH. 

Dr. Minjun Chen
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • predictive toxicology
  • artificial intelligence
  • big data
  • machine learning
  • deep learning
  • toxicogenomics
  • high throughput screening
  • image analysis
  • chemical structure

Related Special Issue

Published Papers (3 papers)

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2024

Jump to: 2023

20 pages, 1896 KiB  
Article
Prediction of Endocrine-Disrupting Chemicals Related to Estrogen, Androgen, and Thyroid Hormone (EAT) Modalities Using Transcriptomics Data and Machine Learning
by Guillaume Ollitrault, Marco Marzo, Alessandra Roncaglioni, Emilio Benfenati, Enrico Mombelli and Olivier Taboureau
Toxics 2024, 12(8), 541; https://doi.org/10.3390/toxics12080541 - 26 Jul 2024
Viewed by 1462
Abstract
Endocrine-disrupting chemicals (EDCs) are chemicals that can interfere with homeostatic processes. They are a major concern for public health, and they can cause adverse long-term effects such as cancer, intellectual impairment, obesity, diabetes, and male infertility. The endocrine system is a complex machinery, [...] Read more.
Endocrine-disrupting chemicals (EDCs) are chemicals that can interfere with homeostatic processes. They are a major concern for public health, and they can cause adverse long-term effects such as cancer, intellectual impairment, obesity, diabetes, and male infertility. The endocrine system is a complex machinery, with the estrogen (E), androgen (A), and thyroid hormone (T) modes of action being of major importance. In this context, the availability of in silico models for the rapid detection of hazardous chemicals is an effective contribution to toxicological assessments. We developed Qualitative Gene expression Activity Relationship (QGexAR) models to predict the propensities of chemically induced disruption of EAT modalities. We gathered gene expression profiles from the LINCS database tested on two cell lines, i.e., MCF7 (breast cancer) and A549 (adenocarcinomic human alveolar basal epithelial). We optimized our prediction protocol by testing different feature selection methods and classification algorithms, including CATBoost, XGBoost, Random Forest, SVM, Logistic regression, AutoKeras, TPOT, and deep learning models. For each EAT endpoint, the final prediction was made according to a consensus prediction as a function of the best model obtained for each cell line. With the available data, we were able to develop a predictive model for estrogen receptor and androgen receptor binding and thyroid hormone receptor antagonistic effects with a consensus balanced accuracy on a validation set ranging from 0.725 to 0.840. The importance of each predictive feature was further assessed to identify known genes and suggest new genes potentially involved in the mechanisms of action of EAT perturbation. Full article
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12 pages, 3044 KiB  
Article
Machine Learning to Predict Drug-Induced Liver Injury and Its Validation on Failed Drug Candidates in Development
by Fahad Mostafa, Victoria Howle and Minjun Chen
Toxics 2024, 12(6), 385; https://doi.org/10.3390/toxics12060385 - 24 May 2024
Viewed by 1340
Abstract
Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and [...] Read more.
Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and procedures to enhance the accuracy of DILI risk prediction for drug candidates under development. In this study, we leveraged a large human dataset to develop machine learning models for assessing DILI risk. The performance of these prediction models was rigorously evaluated using a 10-fold cross-validation approach and an external test set. Notably, the random forest (RF) and multilayer perceptron (MLP) models emerged as the most effective in predicting DILI. During cross-validation, RF achieved an average prediction accuracy of 0.631, while MLP achieved the highest Matthews Correlation Coefficient (MCC) of 0.245. To validate the models externally, we applied them to a set of drug candidates that had failed in clinical development due to hepatotoxicity. Both RF and MLP accurately predicted the toxic drug candidates in this external validation. Our findings suggest that in silico machine learning approaches hold promise for identifying DILI liabilities associated with drug candidates during development. Full article
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2023

Jump to: 2024

27 pages, 5720 KiB  
Article
Artificial Intelligence/Machine Learning-Driven Small Molecule Repurposing via Off-Target Prediction and Transcriptomics
by Mohan Rao, Eric McDuffie and Clifford Sachs
Toxics 2023, 11(10), 875; https://doi.org/10.3390/toxics11100875 - 22 Oct 2023
Cited by 5 | Viewed by 3834
Abstract
The process of discovering small molecule drugs involves screening numerous compounds and optimizing the most promising ones, both in vitro and in vivo. However, approximately 90% of these optimized candidates fail during trials due to unexpected toxicity or insufficient efficacy. Current concepts with [...] Read more.
The process of discovering small molecule drugs involves screening numerous compounds and optimizing the most promising ones, both in vitro and in vivo. However, approximately 90% of these optimized candidates fail during trials due to unexpected toxicity or insufficient efficacy. Current concepts with respect to drug–protein interactions suggest that each small molecule interacts with an average of 6–11 targets. This implies that approved drugs and even discontinued compounds could be repurposed by leveraging their interactions with unintended targets. Therefore, we developed a computational repurposing framework for small molecules, which combines artificial intelligence/machine learning (AI/ML)-based and chemical similarity-based target prediction methods with cross-species transcriptomics information. This repurposing methodology incorporates eight distinct target prediction methods, including three machine learning methods. By using multiple orthogonal methods for a “dataset” composed of 2766 FDA-approved drugs targeting multiple therapeutic target classes, we identified 27,371 off-target interactions involving 2013 protein targets (i.e., an average of around 10 interactions per drug). Relative to the drugs in the dataset, we identified 150,620 structurally similar compounds. The highest number of predicted interactions were for drugs targeting G protein-coupled receptors (GPCRs), enzymes, and kinases with 10,648, 4081, and 3678 interactions, respectively. Notably, 17,283 (63%) of the off-target interactions have been confirmed in vitro. Approximately 4000 interactions had an IC50 of <100 nM for 1105 FDA-approved drugs and 1661 interactions had an IC50 of <10 nM for 696 FDA-approved drugs. Together, the confirmation of numerous predicted interactions and the exploration of tissue-specific expression patterns in human and animal tissues offer insights into potential drug repurposing for new therapeutic applications. Full article
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