Comparative Analysis of Multi-Omics Integration Using Advanced Graph Neural Networks for Cancer Classification

Multi-omics data is increasingly being utilized to advance computational methods for cancer classification. However, multi-omics data integration poses significant challenges due to the high dimensionality, data complexity, and distinct characteristics of various omics types. This study addresses these challenges and evaluates three graph neural network architectures for multi-omics (MO) integration based on graph-convolutional networks (GCN), graph-attention networks (GAT), and graph-transformer networks (GTN) for classifying 31 cancer types and normal tissues. To address the high-dimensionality of multi-omics data, we employed LASSO (Least Absolute Shrinkage and Selection Operator) regression for feature selection, leading to the creation of LASSO-MOGCN, LASSO-MOGAT, and LASSO-MOTGN models. Graph structures for the networks were constructed using gene correlation matrices and protein-protein interaction networks for multi-omics integration of messenger-RNA, micro-RNA, and DNA methylation data. Such data integration enables the networks to dynamically focus on important relationships between biological entities, improving both model performance and interpretability. Among the models, LASSO-MOGAT with a correlation-based graph structure achieved state-of-the-art accuracy (95.9%) and outperformed the LASSO-MOGCN and LASSO-MOTGN models in terms of precision, recall, and F1-score. Our findings demonstrate that integrating multi-omics data in graph-based architectures enhances cancer classification performance by uncovering distinct molecular patterns that contribute to a better understanding of cancer biology and potential biomarkers for disease progression.

LASSO-MOGAT: A Multi-Omics Graph Attention Framework for Cancer Classification

The application of machine learning methods to analyze changes in gene expression patterns has recently emerged as a powerful approach in cancer research, enhancing our understanding of the molecular mechanisms underpinning cancer development and progression. Combining gene expression data with other types of omics data has been reported by numerous works to improve cancer classification outcomes. Despite these advances, effectively integrating high-dimensional multi-omics data and capturing the complex relationships across different biological layers remains challenging. This paper introduces LASSO-MOGAT (LASSO-Multi-Omics Gated ATtention), a novel graph-based deep learning framework that integrates messenger RNA, microRNA, and DNA methylation data to classify 31 cancer types. Utilizing differential expression analysis with LIMMA and LASSO regression for feature selection, and leveraging Graph Attention Networks (GATs) to incorporate protein-protein interaction (PPI) networks, LASSO-MOGAT effectively captures intricate relationships within multi-omics data. Experimental validation using five-fold cross-validation demonstrates the method's precision, reliability, and capacity for providing comprehensive insights into cancer molecular mechanisms. The computation of attention coefficients for the edges in the graph by the proposed graph-attention architecture based on protein-protein interactions proved beneficial for identifying synergies in multi-omics data for cancer classification.

Machine Learning Methods for Cancer Classification Using Gene Expression Data: A Review

Cancer is a term that denotes a group of diseases caused by abnormal growth of cells that can spread in different parts of the body. According to the World Health Organization (WHO), cancer is the second major cause of death after cardiovascular diseases. Gene expression can play a fundamental role in the early detection of cancer, as it is indicative of the biochemical processes in tissue and cells, as well as the genetic characteristics of an organism. Deoxyribonucleic Acid (DNA) microarrays and Ribonucleic Acid (RNA)- sequencing methods for gene expression data allow quantifying the expression levels of genes and produce valuable data for computational analysis. This study reviews recent progress in gene expression analysis for cancer classification using machine learning methods. Both conventional and deep learning-based approaches are reviewed, with an emphasis on the ap-plication of deep learning models due to their comparative advantages for identifying gene patterns that are distinctive for various types of cancers. Relevant works that employ the most commonly used deep neural network architectures are covered, including multi-layer perceptrons, convolutional, recurrent, graph, and transformer networks. This survey also presents an overview of the data collection methods for gene expression analysis and lists important datasets that are commonly used for supervised machine learning for this task. Furthermore, reviewed are pertinent techniques for feature engineering and data preprocessing that are typically used to handle the high dimensionality of gene expression data, caused by a large number of genes present in data samples. The paper concludes with a discussion of future research directions for machine learning-based gene expression analysis for cancer classification.