Liangrui Pan , Xiang Wang , Qingchun Liang , Jiandong Shang , Wenjuan Liu , Liwen Xu , Shaoliang Peng
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引用次数: 0
Abstract
Background and Objective:
Given the high heterogeneity and clinical diversity of cancer, substantial variations exist in multi-omics data and clinical features across different cancer subtypes.
Methods:
We propose a model, named DEDUCE, based on a symmetric multi-head attention encoders (SMAE), for unsupervised contrastive learning to analyze multi-omics cancer data, with the aim of identifying and characterizing cancer subtypes. This model adopts a unsupervised SMAE that can deeply extract contextual features and long-range dependencies from multi-omics data, thereby mitigating the impact of noise. Importantly, DEDUCE introduces a subtype decoupled contrastive learning method based on a multi-head attention mechanism to simultaneously learn features from multi-omics data and perform clustering for identifying cancer subtypes. Subtypes are clustered by calculating the similarity between samples in both the feature space and sample space of multi-omics data. The fundamental concept involves decoupling various attributes of multi-omics data features and learning them as contrasting terms. A contrastive loss function is constructed to quantify the disparity between positive and negative examples, and the model minimizes this difference, thereby promoting the acquisition of enhanced feature representation.
Results:
The DEDUCE model undergoes extensive experiments on simulated multi-omics datasets, single-cell multi-omics datasets, and cancer multi-omics datasets, outperforming 10 deep learning models. The DEDUCE model outperforms state-of-the-art methods, and ablation experiments demonstrate the effectiveness of each module in the DEDUCE model. Finally, we applied the DEDUCE model to identify six cancer subtypes of AML.
Conclusion:
In this paper, we proposed DEDUCE model learns features from multi-omics data through SMAE, and the subtype decoupled contrastive learning consistently optimizes the model for clustering and identifying cancer subtypes. The DEDUCE model demonstrates a significant capability in discovering new cancer subtypes. We applied the DEDUCE model to identify six subtypes of AML. Through the analysis of GO function enrichment, subtype-specific biological functions, and GSEA of AML using the DEDUCE model, the interpretability of the DEDUCE model in identifying cancer subtypes is further enhanced.
期刊介绍:
To encourage the development of formal computing methods, and their application in biomedical research and medical practice, by illustration of fundamental principles in biomedical informatics research; to stimulate basic research into application software design; to report the state of research of biomedical information processing projects; to report new computer methodologies applied in biomedical areas; the eventual distribution of demonstrable software to avoid duplication of effort; to provide a forum for discussion and improvement of existing software; to optimize contact between national organizations and regional user groups by promoting an international exchange of information on formal methods, standards and software in biomedicine.
Computer Methods and Programs in Biomedicine covers computing methodology and software systems derived from computing science for implementation in all aspects of biomedical research and medical practice. It is designed to serve: biochemists; biologists; geneticists; immunologists; neuroscientists; pharmacologists; toxicologists; clinicians; epidemiologists; psychiatrists; psychologists; cardiologists; chemists; (radio)physicists; computer scientists; programmers and systems analysts; biomedical, clinical, electrical and other engineers; teachers of medical informatics and users of educational software.