Combining DNA methylation and RNA sequencing data of cancer for supervised knowledge extraction View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Eleonora Cappelli, Giovanni Felici, Emanuel Weitschek

ABSTRACT

Background: In the Next Generation Sequencing (NGS) era a large amount of biological data is being sequenced, analyzed, and stored in many public databases, whose interoperability is often required to allow an enhanced accessibility. The combination of heterogeneous NGS genomic data is an open challenge: the analysis of data from different experiments is a fundamental practice for the study of diseases. In this work, we propose to combine DNA methylation and RNA sequencing NGS experiments at gene level for supervised knowledge extraction in cancer. Methods: We retrieve DNA methylation and RNA sequencing datasets from The Cancer Genome Atlas (TCGA), focusing on the Breast Invasive Carcinoma (BRCA), the Thyroid Carcinoma (THCA), and the Kidney Renal Papillary Cell Carcinoma (KIRP). We combine the RNA sequencing gene expression values with the gene methylation quantity, as a new measure that we define for representing the methylation quantity associated to a gene. Additionally, we propose to analyze the combined data through tree- and rule-based classification algorithms (C4.5, Random Forest, RIPPER, and CAMUR). Results: We extract more than 15,000 classification models (composed of gene sets), which allow to distinguish the tumoral samples from the normal ones with an average accuracy of 95%. From the integrated experiments we obtain about 5000 classification models that consider both the gene measures related to the RNA sequencing and the DNA methylation experiments. Conclusions: We compare the sets of genes obtained from the classifications on RNA sequencing and DNA methylation data with the genes obtained from the integration of the two experiments. The comparison results in several genes that are in common among the single experiments and the integrated ones (733 for BRCA, 35 for KIRP, and 861 for THCA) and 509 genes that are in common among the different experiments. Finally, we investigate the possible relationships among the different analyzed tumors by extracting a core set of 13 genes that appear in all tumors. A preliminary functional analysis confirms the relation of part of those genes (5 out of 13 and 279 out of 509) with cancer, suggesting to focus further studies on the new individuated ones. More... »

PAGES

22

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13040-018-0184-6

    DOI

    http://dx.doi.org/10.1186/s13040-018-0184-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107853991

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30386434


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