Transformer-based deep learning for accurate detection of multiple base modifications using single molecule real-time sequencing

被引：0

作者：

Hu, Xi ^{[1
,2
,3
]}

Shi, Yuwei ^{[1
,2
,3
]}

Cheng, Suk Hang ^{[1
,2
,3
]}

Huang, Zhaoyang ^{[4
,5
]}

Zhou, Ze ^{[1
,2
,3
]}

Shi, Xiaoyu ^{[4
,5
]}

Zhang, Yi ^{[4
,5
]}

Liu, Jing ^{[1
,2
,3
]}

Ma, Mary-Jane L. ^{[1
,2
,3
]}

Ding, Spencer C. ^{[1
,2
,3
]}

Deng, Jiaen ^{[1
,2
,3
]}

Qiao, Rong ^{[1
,2
,3
]}

Peng, Wenlei ^{[1
,2
,3
]}

Choy, L. Y. Lois ^{[1
,2
,3
,6
]}

Yu, Stephanie C. Y. ^{[1
,2
,3
]}

Lam, W. K. Jacky ^{[1
,2
,3
,6
]}

Chan, K. C. Allen ^{[1
,2
,3
,6
]}

Li, Hongsheng ^{[4
,5
]}

Jiang, Peiyong ^{[1
,2
,3
,6
]}

Lo, Y. M. Dennis ^{[1
,2
,3
,6
]}

机构：

[1] Hong Kong Sci Pk, Ctr Novost, Pak Shek Kok, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China

[3] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China

[4] Chinese Univ Hong Kong, Dept Elect Engn, Shatin, Hong Kong, Peoples R China

[5] Chinese Univ Hong Kong, Multimedia Lab, Shatin, Hong Kong, Peoples R China

[6] Chinese Univ Hong Kong, Prince Wales Hosp, State Key Lab Translat Oncol, Shatin, Hong Kong, Peoples R China

来源：

COMMUNICATIONS BIOLOGY | 2025年 / 8卷 / 01期

关键词：

CELL-FREE DNA; 5-HYDROXYMETHYLCYTOSINE SIGNATURES; 5-METHYLCYTOSINE; METHYLATION;

D O I：

10.1038/s42003-025-08009-8

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We had previously reported a convolutional neural network (CNN) based approach, called the holistic kinetic model (HK model 1), for detecting 5-methylcytosine (5mC) by single molecule real-time sequencing (Pacific Biosciences). In this study, we constructed a hybrid model with CNN and transformer layers, named HK model 2. We improve the area under the receiver operating characteristic curve (AUC) for 5mC detection from 0.91 for HK model 1 to 0.99 for HK model 2. We further demonstrate that HK model 2 can detect other types of base modifications, such as 5-hydroxymethylcytosine (5hmC) and N6-methyladenine (6mA). Using HK model 2 to analyze 5mC patterns of cell-free DNA (cfDNA) molecules, we demonstrate the enhanced detection of patients with hepatocellular carcinoma, with an AUC of 0.97. Moreover, HK model 2-based detection of 6mA enables the detection of jagged ends of cfDNA and the delineation of cellular chromatin structures. HK model 2 is thus a versatile tool expanding the applications of single molecule real-time sequencing in liquid biopsies.

引用

页数：12