Dataset Information

Survival prediction in patients with colon adenocarcinoma via multi-omics data integration using a deep learning algorithm.

ABSTRACT: This study proposed a deep learning (DL) algorithm to predict survival in patients with colon adenocarcinoma (COAD) based on multi-omics integration. The survival-sensitive model was constructed using an autoencoder for DL implementation based on The Cancer Genome Atlas (TCGA) data of patients with COAD. The autoencoder framework was compared to PCA, NMF, t-SNE, and univariable Cox-PH model for identifying survival-related features. The prognostic robustness of the inferred survival risk groups was validated using three independent confirmation cohorts. Differential expression analysis, Pearson's correlation analysis, construction of miRNA-target gene network, and function enrichment analysis were performed. Two risk groups with significant survival differences were identified in TCGA set using the autoencoder-based model (log-rank p-value = 5.51e-07). The autoencoder framework showed superior performance compared to PCA, NMF, t-SNE, and the univariable Cox-PH model based on the C-index, log-rank p-value, and Brier score. The robustness of the classification model was successfully verified in three independent validation sets. There were 1271 differentially expressed genes, 10 differentially expressed miRNAs, and 12 hypermethylated genes between the survival risk groups. Among these, miR-133b and its target genes (GNB4, PTPRZ1, RUNX1T1, EPHA7, GPM6A, BICC1, and ADAMTS5) were used to construct a network. These genes were significantly enriched in ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and glucose metabolism-related pathways. The risk subgroups obtained through a multi-omics data integration pipeline using the DL algorithm had good robustness. miR-133b and its target genes could be potential diagnostic markers. The results would assist in elucidating the possible pathogenesis of COAD.

SUBMITTER: Lv J

PROVIDER: S-EPMC7753845 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Survival prediction in patients with colon adenocarcinoma via multi-omics data integration using a deep learning algorithm.

Lv Jiudi J Wang Junjie J Shang Xiujuan X Liu Fangfang F Guo Shixun S

Bioscience reports 20201201

This study proposed a deep learning (DL) algorithm to predict survival in patients with colon adenocarcinoma (COAD) based on multi-omics integration. The survival-sensitive model was constructed using an autoencoder for DL implementation based on The Cancer Genome Atlas (TCGA) data of patients with COAD. The autoencoder framework was compared to PCA, NMF, t-SNE, and univariable Cox-PH model for identifying survival-related features. The prognostic robustness of the inferred survival risk groups ...[more]

PMID: 33258470

Similar Datasets

Project description:BackgroundBreast cancer is the most prevalent and among the most deadly cancers in females. Patients with breast cancer have highly variable survival lengths, indicating a need to identify prognostic biomarkers for personalized diagnosis and treatment. With the development of new technologies such as next-generation sequencing, multi-omics information are becoming available for a more thorough evaluation of a patient's condition. In this study, we aim to improve breast cancer overall survival prediction by integrating multi-omics data (e.g., gene expression, DNA methylation, miRNA expression, and copy number variations (CNVs)).MethodsMotivated by multi-view learning, we propose a novel strategy to integrate multi-omics data for breast cancer survival prediction by applying complementary and consensus principles. The complementary principle assumes each -omics data contains modality-unique information. To preserve such information, we develop a concatenation autoencoder (ConcatAE) that concatenates the hidden features learned from each modality for integration. The consensus principle assumes that the disagreements among modalities upper bound the model errors. To get rid of the noises or discrepancies among modalities, we develop a cross-modality autoencoder (CrossAE) to maximize the agreement among modalities to achieve a modality-invariant representation. We first validate the effectiveness of our proposed models on the MNIST simulated data. We then apply these models to the TCCA breast cancer multi-omics data for overall survival prediction.ResultsFor breast cancer overall survival prediction, the integration of DNA methylation and miRNA expression achieves the best overall performance of 0.641?±?0.031 with ConcatAE, and 0.63?±?0.081 with CrossAE. Both strategies outperform baseline single-modality models using only DNA methylation (0.583?±?0.058) or miRNA expression (0.616?±?0.057).ConclusionsIn conclusion, we achieve improved overall survival prediction performance by utilizing either the complementary or consensus information among multi-omics data. The proposed ConcatAE and CrossAE models can inspire future deep representation-based multi-omics integration techniques. We believe these novel multi-omics integration models can benefit the personalized diagnosis and treatment of breast cancer patients.

Project description:ObjectivePost-operative biochemical relapse (BCR) continues to occur in a significant percentage of patients with localized prostate cancer (PCa). Current stratification methods are not adequate to identify high-risk patients. The present study exploits the ability of deep learning (DL) algorithms using the H2O package to combine multi-omics data to resolve this problem.MethodsFive-omics data from 417 PCa patients from The Cancer Genome Atlas (TCGA) were used to construct the DL-based, relapse-sensitive model. Among them, 265 (63.5%) individuals experienced BCR. Five additional independent validation sets were applied to assess its predictive robustness. Bioinformatics analyses of two relapse-associated subgroups were then performed for identification of differentially expressed genes (DEGs), enriched pathway analysis, copy number analysis and immune cell infiltration analysis.ResultsThe DL-based model, with a significant difference (P = 6e-9) between two subgroups and good concordance index (C-index = 0.767), were proven to be robust by external validation. 1530 DEGs including 678 up- and 852 down-regulated genes were identified in the high-risk subgroup S2 compared with the low-risk subgroup S1. Enrichment analyses found five hallmark gene sets were up-regulated while 13 were down-regulated. Then, we found that DNA damage repair pathways were significantly enriched in the S2 subgroup. CNV analysis showed that 30.18% of genes were significantly up-regulated and gene amplification on chromosomes 7 and 8 was significantly elevated in the S2 subgroup. Moreover, enrichment analysis revealed that some DEGs and pathways were associated with immunity. Three tumor-infiltrating immune cell (TIIC) groups with a higher proportion in the S2 subgroup (p = 1e-05, p = 8.7e-06, p = 0.00014) and one TIIC group with a higher proportion in the S1 subgroup (P = 1.3e-06) were identified.ConclusionWe developed a novel, robust classification for understanding PCa relapse. This study validated the effectiveness of deep learning technique in prognosis prediction, and the method may benefit patients and prevent relapse by improving early detection and advancing early intervention.

Project description:MotivationMolecular subtyping by integrative modeling of multi-omics and clinical data can help the identification of robust and clinically actionable disease subgroups; an essential step in developing precision medicine approaches.ResultsWe developed a novel outcome-guided molecular subgrouping framework, called Deep Multi-Omics Integrative Subtyping by Maximizing Correlation (DeepMOIS-MC), for integrative learning from multi-omics data by maximizing correlation between all input -omics views. DeepMOIS-MC consists of two parts: clustering and classification. In the clustering part, the preprocessed high-dimensional multi-omics views are input into two-layer fully connected neural networks. The outputs of individual networks are subjected to Generalized Canonical Correlation Analysis loss to learn the shared representation. Next, the learned representation is filtered by a regression model to select features that are related to a covariate clinical variable, for example, a survival/outcome. The filtered features are used for clustering to determine the optimal cluster assignments. In the classification stage, the original feature matrix of one of the -omics view is scaled and discretized based on equal frequency binning, and then subjected to feature selection using RandomForest. Using these selected features, classification models (for example, XGBoost model) are built to predict the molecular subgroups that were identified at clustering stage. We applied DeepMOIS-MC on lung and liver cancers, using TCGA datasets. In comparative analysis, we found that DeepMOIS-MC outperformed traditional approaches in patient stratification. Finally, we validated the robustness and generalizability of the classification models on independent datasets. We anticipate that the DeepMOIS-MC can be adopted to many multi-omics integrative analyses tasks.Availability and implementationSource codes for PyTorch implementation of DGCCA and other DeepMOIS-MC modules are available at GitHub (https://github.com/duttaprat/DeepMOIS-MC).Supplementary informationSupplementary data are available at Bioinformatics Advances online.

Dataset Information

Survival prediction in patients with colon adenocarcinoma via multi-omics data integration using a deep learning algorithm.

Publications

Survival prediction in patients with colon adenocarcinoma via multi-omics data integration using a deep learning algorithm.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets