PAHs carcinogenicity prediction method and prediction model based on 2D molecular descriptors

Abstract

The invention discloses a PAHs carcinogenicity prediction method and prediction model based on 2D molecular descriptors. According to an OECD principle, based on a simple 2D molecular descriptor, chemometrics QSAR modeling is carried out to predict carcinogenicity of PAHs to rodents. Six QSAR models for PAHs carcinogenicity of female rats, male rats, female mice, male mice, and rats and mice have been established and validated using a plurality of statistical validation criteria. Mechanism analysis clearly shows correlation between descriptors and carcinogenicity, and some descriptors existing in different models at the same time show that similar action mechanisms may exist. In addition, the invention also establishes two iQCCR models which are used for filling interspecific data blank. According to the method, the QSAR model and the iQCCR model are applied to carcinogenicity prediction of hundreds of untested PAHs, the prediction quality of each molecule is evaluated, and priority compounds can be screened out according to the carcinogenicity of the PAHs, so that the method has important significance on risk assessment under a supervision framework.

Description

technical field [0001] The invention relates to a PAHs carcinogenicity prediction method and prediction model based on 2D molecular descriptors, belonging to the technical field of compound carcinogenicity prediction. Background technique [0002] Cancer is one of the leading causes of death in countries around the world and a key factor in prolonging life. According to the WHO Global Health Assessment 2020, cancer is the first or second leading cause of death among people under 70 in 112 of 185 countries, and among those under 70 in 23 countries third or fourth leading cause of death. In fact, many cancer deaths can be attributed to potentially modifiable risk factors, and if carcinogens and carcinogenic mechanisms are well understood, and effective preventive strategies are implemented, half of all cancers can be avoided. Among these risk factors, exposure to exogenous chemicals is one of the most important ones. IARC (International Agency for Research on Cancer) lists ...

AI Technical Summary

Problems solved by technology

However, the animal experimental methods used to study carcinogenicity have the following limitations: time-consuming (typically 18-36 months), and the single-standard test is extremely expensive; animal welfare and ethical issues, which must involve a large number of animals to ensure a statistically significant with remarkable results

Several QSAR models for non-similar chemicals have been established, but their predictive power is generally weak and lack mechanistic explanation compared with QSAR models for similar chemicals

In addition, although some QSAR prediction models for similar chemicals have been established, such as nitro, aromatic amines, N-nitrosamines, and aromatic nitrogen compounds, the QSAR models for the carcinogenicity of PAHs to rodents have not been reported, and few models are available. are classification models

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