Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals.

Journal: Toxicology letters
PMID:

Abstract

Although many neurotoxicity prediction studies of food additives have been developed, they are applicable in a qualitative way. We aimed to develop a novel prediction score that is described quantitatively and precisely. We examined cell viability, reactive oxygen species activity, intracellular calcium and RNA transcription level of potential prediction related genes to develop a high-throughput neurotoxicity test method in vitro to screen the neurotoxicity of hazardous factors in food using AI-based machine learning. We trained artificial intelligence models (random forest and neural network) to predict neurotoxicity precisely, establishing a universal classification assessment score (CA-Score) that relies on the expression status of only 13 of prediction related genes. The CA-Score system is almost universally applicable to food risk factors (p<0.05) in a manner independent of platform (microarray or RNA sequencing) by being compared with cut-off value 23.487 to judge whether it's neurotoxic or not. We finally validated our prediction with the external validation of CA-Score on neural precursor cells derived from embryonic stem cells. Therefore, we draw a conclusion that the AI-based machine learning including neural network and random forest is likely to provide a useful tool for large-scale screening of neurotoxicity in food risk factors.

Authors

  • Xiaolan Li
    Laboratory of Allergy and Precision Medicine Chengdu Institute of Respiratory Health the Third People's Hospital of Chengdu Affiliated Hospital of Southwest Jiaotong University Chengdu China.
  • Wei Cheng
    Department of Dental Implantology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
  • Shoufei Yang
    School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, PR China.
  • Fan Liang
  • Hui Wang
    Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • Yan Feng
    Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA.
  • Yan Wang
    College of Animal Science and Technology, Beijing University of Agriculture, Beijing, China.