Lung tumor discrimination by deep neural network model CanDo via DNA methylation in bronchial lavage

• Published in: iScience Vol. 27; no. 6; p. 110079
• Main Authors: Yu, Zezhong, Li, Jieyi, Deng, Yi, Li, Chun, Ye, Maosong, Zhang, Yong, Huang, Yuqing, Wang, Xintao, Zhao, Xiaokai, Liu, Jie, Liu, Zilong, Yin, Xia, Mei, Lijiang, Hou, Yingyong, Hu, Qin, Huang, Yao, Wang, Rongping, Fu, Huiyu, Qiu, Rumeng, Xu, Jiahuan, Gong, Ziying, Zhang, Daoyun, Zhang, Xin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2024; Elsevier
• Subjects: Cell; Computing methodology; Disease; Disease; Computing methodology; Cell
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110079

Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing. The Recursive Feature Elimination Cross-Validation and deep neural network algorithm established the CanDo classification model, which incorporated 11 methylation features (including 8 specific to the TBR1 gene), demonstrating a sensitivity of 98.6% and specificity of 97.8%. In contrast, bronchoscopic rapid on-site evaluation (bronchoscopic-ROSE) had lower sensitivity (87.7%) and specificity (80%). Further validation in 33 individuals confirmed CanDo’s discriminatory potential, particularly in challenging cases for bronchoscopic-ROSE due to pathological complexity. CanDo serves as a valuable complement to bronchoscopy for the discriminatory diagnosis and stratified management of lung tumors utilizing BWF specimens. [Display omitted] •Meta-analysis found 13 genes significant in methylation for distinguishing lung cancer•Multiplex PCR with targeted methylation sequencing enhanced detection sensitivity•BWF methylation test had 98.6% sensitivity, 97.8% specificity in lung tumor diagnosis•TBR1 gene methylation may be important in the occurrence of lung cancer Disease; Cell; Computing methodology