Abstract

BackgroundLong noncoding RNAs (lncRNAs) are widely involved in the initiation and development of cancer. Although some computational methods have been proposed to identify cancer-related lncRNAs, there is still a demanding to improve the prediction accuracy and efficiency. In addition, the quick-update data of cancer, as well as the discovery of new mechanism, also underlay the possibility of improvement of cancer-related lncRNA prediction algorithm. In this study, we introduced CRlncRC, a novel Cancer-Related lncRNA Classifier by integrating manifold features with five machine-learning techniques.ResultsCRlncRC was built on the integration of genomic, expression, epigenetic and network, totally in four categories of features. Five learning techniques were exploited to develop the effective classification model including Random Forest (RF), Naïve bayes (NB), Support Vector Machine (SVM), Logistic Regression (LR) and K-Nearest Neighbors (KNN). Using ten-fold cross-validation, we showed that RF is the best model for classifying cancer-related lncRNAs (AUC = 0.82). The feature importance analysis indicated that epigenetic and network features play key roles in the classification. In addition, compared with other existing classifiers, CRlncRC exhibited a better performance both in sensitivity and specificity. We further applied CRlncRC to lncRNAs from the TANRIC (The Atlas of non-coding RNA in Cancer) dataset, and identified 121 cancer-related lncRNA candidates. These potential cancer-related lncRNAs showed a certain kind of cancer-related indications, and many of them could find convincing literature supports.ConclusionsOur results indicate that CRlncRC is a powerful method for identifying cancer-related lncRNAs. Machine-learning-based integration of multiple features, especially epigenetic and network features, had a great contribution to the cancer-related lncRNA prediction. RF outperforms other learning techniques on measurement of model sensitivity and specificity. In addition, using CRlncRC method, we predicted a set of cancer-related lncRNAs, all of which displayed a strong relevance to cancer as a valuable conception for the further cancer-related lncRNA function studies.

Highlights

  • Long noncoding RNAs are widely involved in the initiation and development of cancer

  • We showed that machine learning-based integration of multiple features had a great contribution to the cancer-related Long non-coding RNA (lncRNA) prediction, wherein epigenetic and genomic features play key roles in the classification

  • The positive dataset consisted of 158 experimentally-validated cancer-related lncRNAs curated from the scientific literature (Additional file 1); while the negative was randomly sampled from long intergenic noncoding RNAs whose 10 kb upstream and downstream

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Summary

Introduction

Long noncoding RNAs (lncRNAs) are widely involved in the initiation and development of cancer. Several methods have been designed to identify potential cancer-related lncRNAs. For example, Zhao et al developed a naïve-Bayesian-based classifier to identify cancer-related lncRNAs by integrating both genome, regulome and transcriptome data, and identified 707 potential cancer-related lncRNAs [10]. Lanzós Andrés et al conceived a tool (ExInAtor) to identify cancer driver lncRNA genes with an excess load of somatic single nucleotide variants (SNVs) and found 15 high-confidence candidates: 9 novel and 6 known cancer-related lncRNA genes [11]. This kind of studies is still at infancy, and would be bound to a measure of limitations in the aspects of accuracy and sensitivity. Different algorithms of the classification model should be developed reasonably, and important features should be further explored systematically, in order to advance the sensitivity and accuracy when we are seeking the cancer-related lncRNAs

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