Dataset Information

Combining Supervised and Unsupervised Learning for Improved miRNA Target Prediction.

ABSTRACT: MicroRNAs (miRNAs) are short non-coding RNAs which bind to mRNAs and regulate their expression. MiRNAs have been found to be associated with initiation and progression of many complex diseases. Investigating miRNAs and their targets can thus help develop new therapies by designing anti-miRNA oligonucleotides. While existing computational approaches can predict miRNA targets, these predictions have low accuracy. In this paper, we propose a two-step approach to refine the results of sequence-based prediction algorithms. The first step, which is based on our previous work, uses an ensemble learning approach that combines multiple existing methods. The second step utilizes support vector machine (SVM) classifiers in one- and two-class modes to infer miRNA-mRNA interactions based on both binding features, as well as network features extracted from gene regulatory network. Experimental results using two real data sets from TCGA indicate that the use of two-class SVM classification significantly improves the precision of miRNA-mRNA prediction.

SUBMITTER: Sedaghat N

PROVIDER: S-EPMC7001746 | biostudies-literature | 2018 Sep-Oct

REPOSITORIES: biostudies-literature

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Publications

Combining Supervised and Unsupervised Learning for Improved miRNA Target Prediction.

Sedaghat Nafiseh N Fathy Mahmood M Modarressi Mohammad Hossein MH Shojaie Ali A

IEEE/ACM transactions on computational biology and bioinformatics 20170713 5

MicroRNAs (miRNAs) are short non-coding RNAs which bind to mRNAs and regulate their expression. MiRNAs have been found to be associated with initiation and progression of many complex diseases. Investigating miRNAs and their targets can thus help develop new therapies by designing anti-miRNA oligonucleotides. While existing computational approaches can predict miRNA targets, these predictions have low accuracy. In this paper, we propose a two-step approach to refine the results of sequence-based ...[more]

PMID: 28715336

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Project description:BackgroundData mining of electronic health records (EHRs) has a huge potential for improving clinical decision support and to help healthcare deliver precision medicine. Unfortunately, the rule-based and machine learning-based approaches used for natural language processing (NLP) in healthcare today all struggle with various shortcomings related to performance, efficiency, or transparency.MethodsIn this paper, we address these issues by presenting a novel method for NLP that implements unsupervised learning of word embeddings, semi-supervised learning for simplified and accelerated clinical vocabulary and concept building, and deterministic rules for fine-grained control of information extraction. The clinical language is automatically learnt, and vocabulary, concepts, and rules supporting a variety of NLP downstream tasks can further be built with only minimal manual feature engineering and tagging required from clinical experts. Together, these steps create an open processing pipeline that gradually refines the data in a transparent way, which greatly improves the interpretable nature of our method. Data transformations are thus made transparent and predictions interpretable, which is imperative for healthcare. The combined method also has other advantages, like potentially being language independent, demanding few domain resources for maintenance, and able to cover misspellings, abbreviations, and acronyms. To test and evaluate the combined method, we have developed a clinical decision support system (CDSS) named Information System for Clinical Concept Searching (ICCS) that implements the method for clinical concept tagging, extraction, and classification.ResultsIn empirical studies the method shows high performance (recall 92.6%, precision 88.8%, F-measure 90.7%), and has demonstrated its value to clinical practice. Here we employ a real-life EHR-derived dataset to evaluate the method's performance on the task of classification (i.e., detecting patient allergies) against a range of common supervised learning algorithms. The combined method achieves state-of-the-art performance compared to the alternative methods we evaluate. We also perform a qualitative analysis of common word embedding methods on the task of word similarity to examine their potential for supporting automatic feature engineering for clinical NLP tasks.ConclusionsBased on the promising results, we suggest more research should be aimed at exploiting the inherent synergies between unsupervised, supervised, and rule-based paradigms for clinical NLP.

Project description:BackgroundVirtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites.ResultsWe developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms.ConclusionOnly a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila, suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org.

Dataset Information

Combining Supervised and Unsupervised Learning for Improved miRNA Target Prediction.

Publications

Combining Supervised and Unsupervised Learning for Improved miRNA Target Prediction.

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