A plethora of natural and synthetic chemical compounds are industrially distributed around the world. However, shockingly, the majority of these chemicals have not been comprehensively evaluated for their safety and toxicity due to limitations of standard toxicity testing approaches. Such limitations are due to these methods being performed by in vivo or in vitro analysis for each chemical using experimental analysis or cultured cells, which are often costly and time-consuming processes. Thus, there is a dire need for novel toxicity testing approaches that are more time- and cost-efficient.

High-throughput screening provides a far more efficient alternative to these conventional approaches and has enabled the volume of chemical toxicity data to expand significantly over recent years. However, standard protocols for data analysis are not able to efficiently process such large datasets and highlight a need for novel analytical methods to overcome this challenge. Recently, Deep Learning, a machine learning method using artificial intelligence, has demonstrated the incredible ability to recognize images and extract features from vast input datasets using deep neural networks (DNN). DNNs can extract information from large datasets, automatically, and make high accuracy prediction models utilizing a softmax function that converts an arbitrary numeric output into a “probability value”.

Deep learning has proven to be a useful tool for building Quantitative Structure-Activity Relationship (QSAR) models, defined by quantitative relation build between chemical structure and biological activity used to predict various types of toxicity from large datasets without usage of experimental animals. But, in order to establish a prediction model with high performance, it is first necessary to develop methods to select and extract specific molecular descriptors that provide chemical information contained in the molecules. This approach of using chemical structures as images in the toxicological fields would be a powerful tool to make strong prediction models.

There is a preponderance of evidence that the progression from a large subset of human heart diseases to heart failure (HF) involves increased proteotoxic stress (IPTS); and experimental studies are demonstrating that targeting IPTS could be a novel and effective strategy for HF intervention, including both HF with reduced ejection fraction (EF) and HF with preserved EF. However, the significance of proteotoxicity in cardiac pathophysiology remains underappreciated and, importantly, none of the current clinical therapies for HF are intended to target IPTS yet, calling for increasing our effort to educate the biomedical community on this nascent and exciting field.

In the past several years, exciting new progresses have been made at multiple levels (e.g., proteomics, molecular/cell biology, and integrative physiology) regarding the underlying causes and mechanisms of action of IPTS in diseased hearts as well as novel strategies to facilitate the clearance of toxic protein species by both proteasomes and lysosomes. This Research Topic is intended to timely highlight these cutting-edge multi-disciplinary sciences, stimulate new ideas, entice more researchers to join the field, and move forward this underappreciated but highly significant field. Both Original Research and Review articles are welcomed.

Media contact:

Larry Tyler

Managing Editor

Journal of Clinical Toxicology

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