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Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli.

ABSTRACT: A significant obstacle in training predictive cell models is the lack of integrated data sources. We develop semi-supervised normalization pipelines and perform experimental characterization (growth, transcriptional, proteome) to create Ecomics, a consistent, quality-controlled multi-omics compendium for Escherichia coli with cohesive meta-data information. We then use this resource to train a multi-scale model that integrates four omics layers to predict genome-wide concentrations and growth dynamics. The genetic and environmental ontology reconstructed from the omics data is substantially different and complementary to the genetic and chemical ontologies. The integration of different layers confers an incremental increase in the prediction performance, as does the information about the known gene regulatory and protein-protein interactions. The predictive performance of the model ranges from 0.54 to 0.87 for the various omics layers, which far exceeds various baselines. This work provides an integrative framework of omics-driven predictive modelling that is broadly applicable to guide biological discovery.

SUBMITTER: Kim M

PROVIDER: S-EPMC5059772 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli.

Kim Minseung M Rai Navneet N Zorraquino Violeta V Tagkopoulos Ilias I

Nature communications 20161007

A significant obstacle in training predictive cell models is the lack of integrated data sources. We develop semi-supervised normalization pipelines and perform experimental characterization (growth, transcriptional, proteome) to create Ecomics, a consistent, quality-controlled multi-omics compendium for Escherichia coli with cohesive meta-data information. We then use this resource to train a multi-scale model that integrates four omics layers to predict genome-wide concentrations and growth dy ...[more]

PMID: 27713404

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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.

Dataset Information

Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli.

Publications

Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli.

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