Motivation: Precise prediction of cancer subtypes is of significant importance in cancer diagnosis and treatment. Disease etiology is complicated existing at different omics levels; hence integrative analysis provides a very effective way to improve our understanding of cancer. Results: We propose a novel computational framework, named Deep Subspace Mutual Learning (DSML). DSML has the capability to simultaneously learn the subspace structures in each available omics data and in overall multi-omics data by adopting deep neural networks, which thereby facilitates the subtype’s prediction via clustering on multi-level, single-level and partial-level omics data. Extensive experiments are performed in five different cancers on three levels of omics data from The Cancer Genome Atlas. The experimental analysis demonstrates that DSML delivers comparable or even better results than many state-of-the-art integrative methods. Availability and implementation: An implementation and documentation of the DSML is publicly available at https://github.com/polytechnicXTT/Deep-Subspace-Mutual-Learning.git.
Cancer is a molecular complex and heterogeneous disease. Each type of cancer is usually composed of several subtypes with different treatment responses and clinical outcomes. Therefore, subtyping is a crucial step in cancer diagnosis and therapy. The rapid advances in high-throughput sequencing technologies provide an increasing amount of multi-omics data, which benefits our understanding of cancer genetic architecture, and yet poses new challenges in multi-omics data integration. We propose a graph convolutional network model, called MRGCN for multi-omics data integrative representation. MRGCN simultaneously encodes and reconstructs multiple omics expression and similarity relationships into a shared latent embedding space. In addition, MRGCN adopts an indicator matrix to denote the situation of missing values in partial omics, so that the full and partial multi-omics processing procedures are combined in a unified framework. Experimental results on 11 multi-omics datasets show that cancer subtypes obtained by MRGCN with superior enriched clinical parameters and log-rank test P-values in survival analysis over many typical integrative methods. https://github.com/Polytech-bioinf/MRGCN.git https://figshare.com/articles/software/MRGCN/23058503.
4 November 2019 in IEEE/ACM Transactions on Computational Biology and Bioinformatics
One type of cancer usually consists of several subtypes with distinct clinical implications, thus the cancer subtype prediction is an important task in disease diagnosis and therapy. Utilizing one type of data from molecular layers in biological system to predict is difficult to bridge the cancer genome to cancer phenotypes, since the genome is neither simple nor independent but rather complicated and dysregulated from multiple molecular mechanisms. Similarity Network Fusion (SNF) has been recently proposed to integrate diverse omics data for improving the understanding of tumorigenesis. SNF adopts Euclidean distance to measure the similarity between patients, which shows some limitations. In this paper, we introduce a novel prediction technique as an extension of SNF, namely Deep Subspace Fusion Clustering (DSFC). DSFC utilizes auto-encoder and data self-expressiveness approaches to guide a deep subspace model, which can achieve effective expression of discriminative similarity between patients. As a result, the dissimilarity between inter-cluster is delivered and enhanced compactness of intra-cluster is achieved at the same time. The validity of DSFC is examined by extensive simulations over six different cancer through three levels omics data. The survival analysis demonstrates that DSFC delivers comparable or even better results than many state-of-the-art integrative methods.
Cancer is a heterogeneous group of diseases. Cancer subtyping is a crucial and critical step to diagnosis, prognosis and treatment. Since high-throughput sequencing technologies provide an unprecedented opportunity to rapidly collect multi-omics data for the same individuals, an urgent need in current is how to effectively represent and integrate these multi-omics data to achieve clinically meaningful cancer subtyping. We propose a novel deep learning model, called Deep Structure Integrative Representation (DSIR), for cancer subtypes dentification by integrating representation and clustering multi-omics data. DSIR simultaneously captures the global structures in sparse subspace and local structures in manifold subspace from multi-omics data and constructs a consensus similarity matrix by utilizing deep neural networks. Extensive tests are performed in 12 different cancers on three levels of omics data from The Cancer Genome Atlas. The results demonstrate that DSIR obtains more significant performances than the state-of-the-art integrative methods. https://github.com/Polytech-bioinf/Deep-structure-integrative-representation.git Supplementary data are available at Bioinformatics online.
Cancer is a highly diverse group of diseases, and each type of cancer can be further divided into various subtypes according to specific characteristics, cellular origins, and molecular markers. Subtyping helps in tailoring treatment and prognosis accuracy. However, the existing studies are more concerned with integrating different omics data to discover potential connections, but ignoring the relationships between consensus information and individual information within each omics level during the integration process. To this end, we propose a novel fusion-free method called multi-view multi-level contrastive graph convolutional network (M$^{2}$CGCN) for cancer subtyping. M$^{2}$CGCN learns multi-level features, i.e. high-level and low-level features, respectively. The low-level features from each view capture the intrinsic information in each omics by reconstruction of node attribute and graph structures. The high-level features achieve cancer subtyping via contrastive learning. Comprehensive experiments were performed on 34 multi-omics cancer datasets. The findings indicate that M$^{2}$CGCN achieves results comparable to or surpassing many state-of-the-art methods.