Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step.

High throughput sequencing RNA-sequencing technologies and modern in silico techniques have expanded our knowledge on short non-coding RNAs. These sequences were initially split into various categories based on their cellular functionality and their sequential, thermodynamic and structural properties believing that their sequence can be used as an identifier to distinguish them. However, recent evidence has indicated that the same sequences can act and function as more than one type of non-coding RNAs with a striking example of mature mi-croRNA sequences which can also be transfer RNA fragments. Most of the existing computational methods for the prediction of non-coding RNA sequences have emphasized on the prediction of only one type of noncoding RNAs and even the ones designed for multiclassification do not support multiple labeling and are thus not able to assign a sequence to more than one non-coding RNA type. In the present paper, we introduce a new multilabel-multiclass method based on the combination of multiobjective evolutionary algorithms and multi-label implementations of Random Forests to optimize the feature selection process and assign short RNA sequences to one or more non-coding RNA types. The overall methodology clearly outperformed other machine learning techniques which were used for the same purpose and it is applicable to data coming from RNA-sequencing experiments.

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The diagnostic and prognostic value of miRNAs in cutaneous melanoma (CM) has been broadly studied and supported by advanced bioinformatics tools. From early studies using miRNA arrays with several limitations, to the recent NGS-derived miRNA expression profiles, an accurate diagnostic panel of a comprehensive pre-specified set of miRNAs that could aid timely identification of specific cancer stages is still elusive, mainly because of the heterogeneity of the approaches and the samples. Herein, we summarize the existing studies that report several miRNAs as important diagnostic and prognostic biomarkers in CM. Using publicly available NGS data, we analyzed the correlation of specific miRNA expression profiles with the expression signatures of known gene targets. Combining network analytics with machine learning, we developed specific non-linear classification models that could successfully predict CM recurrence and metastasis, based on two newly identified miRNA signatures. Subsequent unbiased analyses and independent test sets (i.e., a dataset not used for training, as a validation cohort) using our prediction models resulted in 73.85% and 82.09% accuracy in predicting CM recurrence and metastasis, respectively. Overall, our approach combines detailed analysis of miRNA profiles with heuristic optimization and machine learning, which facilitates dimensionality reduction and optimization of the prediction models. Our approach provides an improved prediction strategy that could serve as an auxiliary tool towards precision treatment.

Purpose: Chronic pain is a life changing condition, and non-opioid treatments have been lately introduced to overcome the addictive nature of opioid therapies and their side effects. In the present study, we explore the potential of machine learning methods to discriminate chronic pain patients into ones who will benefit from such a treatment and ones who will not, aiming to personalize their treatment. Patients and Methods: In the current study, data from the OPERA study were used, with 631 chronic pain patients answering the Brief Pain Inventory (BPI) validated questionnaire along with supplemental questions before and after a follow-up period. A novel machine learning approach combining multi-objective optimization and support vector regression was used to build prediction models which can predict, using responses in the baseline, the four different outcomes of the study: total drugs change, total interference change, total severity change, and total complaints change. Data were split to training (504 patients) and testing (127 patients) sets and all results are measured on the independent test set. Results: The machine learning models extracted in the present study significantly overcame other state of the art machine learning methods which were deployed for comparative purposes. The experimental results indicated that the machine learning models can predict the outcomes of this study with considerably high accuracy (AUC 73.8-87.2%) and this allowed their incorporation in a decision support system for the selection of the treatment of chronic pain patients. Conclusion: Results of this study revealed the potential of machine learning for an individualized medicine application for chronic pain therapies. Topical analgesics treatment were proven to be, in general, beneficial but carefully selecting with the suggested individualized medicine decision support system was able to decrease by approximately 10% the patients which would have been subscribed with topical analgesics without having benefits from it.