Dataset Information

Early detection of hepatocellular carcinoma via no end-repair enzymatic methylation sequencing of cell-free DNA and pre-trained neural network.

ABSTRACT:

Background

Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC.

Methods

We developed a low DNA damage and high-fidelity methylation detection method called No End-repair Enzymatic Methyl-seq (NEEM-seq). We further developed a read-level neural detection model called DeepTrace that can better identify HCC-derived sequencing reads through a pre-trained and fine-tuned neural network. After pre-training on 11 million reads from NEEM-seq, DeepTrace was fine-tuned using 1.2 million HCC-derived reads from tumor tissue DNA after noise reduction, and 2.7 million non-tumor reads from non-tumor cfDNA. We validated the model using data from 130 individuals with cfDNA whole-genome NEEM-seq at around 1.6X depth.

Results

NEEM-seq overcomes the drawbacks of traditional enzymatic methylation sequencing methods by avoiding the introduction of unmethylation errors in cfDNA. DeepTrace outperformed other models in identifying HCC-derived reads and detecting HCC individuals. Based on the whole-genome NEEM-seq data of cfDNA, our model showed high accuracy of 96.2%, sensitivity of 93.6%, and specificity of 98.5% in the validation cohort consisting of 62 HCC patients, 48 liver disease patients, and 20 healthy individuals. In the early stage of HCC (BCLC 0/A and TNM I), the sensitivity of DeepTrace was 89.6 and 89.5% respectively, outperforming Alpha Fetoprotein (AFP) which showed much lower sensitivity in both BCLC 0/A (50.5%) and TNM I (44.7%).

Conclusions

By combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications. DeepTrace: https://github.com/Bamrock/DeepTrace.

SUBMITTER: Deng Z

PROVIDER: S-EPMC10631027 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Early detection of hepatocellular carcinoma via no end-repair enzymatic methylation sequencing of cell-free DNA and pre-trained neural network.

Deng Zhenzhong Z Ji Yongkun Y Han Bing B Tan Zhongming Z Ren Yuqi Y Gao Jinghan J Chen Nan N Ma Cong C Zhang Yichi Y Yao Yunhai Y Lu Hong H Huang Heqing H Xu Midie M Chen Lei L Zheng Leizhen L Gu Jianchun J Xiong Deyi D Zhao Jianxin J Gu Jinyang J Chen Zutao Z Wang Ke K

Genome medicine 20231108 1

<h4>Background</h4>Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC.<h4>Methods</h4 ...[more]

PMID: 37936230

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Project description:Histopathological images contain rich phenotypic descriptions of the molecular processes underlying disease progression. Convolutional neural networks, state-of-the-art image analysis techniques in computer vision, automatically learn representative features from such images which can be useful for disease diagnosis, prognosis, and subtyping. Hepatocellular carcinoma (HCC) is the sixth most common type of primary liver malignancy. Despite the high mortality rate of HCC, little previous work has made use of CNN models to explore the use of histopathological images for prognosis and clinical survival prediction of HCC. We applied three pre-trained CNN models-VGG 16, Inception V3 and ResNet 50-to extract features from HCC histopathological images. Sample visualization and classification analyses based on these features showed a very clear separation between cancer and normal samples. In a univariate Cox regression analysis, 21.4% and 16% of image features on average were significantly associated with overall survival (OS) and disease-free survival (DFS), respectively. We also observed significant correlations between these features and integrated biological pathways derived from gene expression and copy number variation. Using an elastic net regularized Cox Proportional Hazards model of OS constructed from Inception image features, we obtained a concordance index (C-index) of 0.789 and a significant log-rank test (p = 7.6E-18). We also performed unsupervised classification to identify HCC subgroups from image features. The optimal two subgroups discovered using Inception model image features showed significant differences in both overall (C-index = 0.628 and p = 7.39E-07) and DFS (C-index = 0.558 and p = 0.012). Our work demonstrates the utility of extracting image features using pre-trained models by using them to build accurate prognostic models of HCC as well as highlight significant correlations between these features, clinical survival, and relevant biological pathways. Image features extracted from HCC histopathological images using the pre-trained CNN models VGG 16, Inception V3 and ResNet 50 can accurately distinguish normal and cancer samples. Furthermore, these image features are significantly correlated with survival and relevant biological pathways.

Dataset Information

Early detection of hepatocellular carcinoma via no end-repair enzymatic methylation sequencing of cell-free DNA and pre-trained neural network.

Background

Methods

Results

Conclusions

Publications

Early detection of hepatocellular carcinoma via no end-repair enzymatic methylation sequencing of cell-free DNA and pre-trained neural network.

Similar Datasets

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