BackgroundAn open challenge in translational bioinformatics is the analysis of sequenced metagenomes from various environmental samples. Of course, several studies demonstrated the 16S ribosomal RNA could be considered as a barcode for bacteria classification at the genus level, but till now it is hard to identify the correct composition of metagenomic data from RNA-seq short-read data. 16S short-read data are generated using two next generation sequencing technologies, i.e. whole genome shotgun (WGS) and amplicon (AMP); typically, the former is filtered to obtain short-reads belonging to a 16S shotgun (SG), whereas the latter take into account only some specific 16S hypervariable regions. The above mentioned two sequencing technologies, SG and AMP, are used alternatively, for this reason in this work we propose a deep learning approach for taxonomic classification of metagenomic data, that can be employed for both of them.ResultsTo test the proposed pipeline, we simulated both SG and AMP short-reads, from 1000 16S full-length sequences. Then, we adopted a k-mer representation to map sequences as vectors into a numerical space. Finally, we trained two different deep learning architecture, i.e., convolutional neural network (CNN) and deep belief network (DBN), obtaining a trained model for each taxon. We tested our proposed methodology to find the best parameters configuration, and we compared our results against the classification performances provided by a reference classifier for bacteria identification, known as RDP classifier. We outperformed the RDP classifier at each taxonomic level with both architectures. For instance, at the genus level, both CNN and DBN reached 91.3% of accuracy with AMP short-reads, whereas RDP classifier obtained 83.8% with the same data.ConclusionsIn this work, we proposed a 16S short-read sequences classification technique based on k-mer representation and deep learning architecture, in which each taxon (from phylum to genus) generates a classification model. Experimental results confirm the proposed pipeline as a valid approach for classifying bacteria sequences; for this reason, our approach could be integrated into the most common tools for metagenomic analysis. According to obtained results, it can be successfully used for classifying both SG and AMP data.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2182-6) contains supplementary material, which is available to authorized users.

MotivationNon-coding RNA (ncRNA) are small non-coding sequences involved in gene expression regulation of many biological processes and diseases. The recent discovery of a large set of different ncRNAs with biologically relevant roles has opened the way to develop methods able to discriminate between the different ncRNA classes. Moreover, the lack of knowledge about the complete mechanisms in regulative processes, together with the development of high-throughput technologies, has required the help of bioinformatics tools in addressing biologists and clinicians with a deeper comprehension of the functional roles of ncRNAs. In this work, we introduce a new ncRNA classification tool, nRC (non-coding RNA Classifier). Our approach is based on features extraction from the ncRNA secondary structure together with a supervised classification algorithm implementing a deep learning architecture based on convolutional neural networks.ResultsWe tested our approach for the classification of 13 different ncRNA classes. We obtained classification scores, using the most common statistical measures. In particular, we reach an accuracy and sensitivity score of about 74%.ConclusionThe proposed method outperforms other similar classification methods based on secondary structure features and machine learning algorithms, including the RNAcon tool that, to date, is the reference classifier. nRC tool is freely available as a docker image at https://hub.docker.com/r/tblab/nrc/. The source code of nRC tool is also available at https://github.com/IcarPA-TBlab/nrc.

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BackgroundMicroRNAs (miRNAs) are important key regulators in multiple cellular functions, due to their a crucial role in different physiological processes. MiRNAs are differentially expressed in specific tissues, during specific cell status, or in different diseases as tumours. RNA sequencing (RNA-seq) is a Next Generation Sequencing (NGS) method for the analysis of differential gene expression. Using machine learning algorithms, it is possible to improve the functional significance interpretation of miRNA in the analysis and interpretation of data from RNA-seq. Furthermore, we tried to identify some patterns of deregulated miRNA in human breast cancer (BC), in order to give a contribution in the understanding of this type of cancer at the molecular level.ResultsWe adopted a biclustering approach, using the Iterative Signature Algorithm (ISA) algorithm, in order to evaluate miRNA deregulation in the context of miRNA abundance and tissue heterogeneity. These are important elements to identify miRNAs that would be useful as prognostic and diagnostic markers. Considering a real word breast cancer dataset, the evaluation of miRNA differential expressions in tumours versus healthy tissues evidenced 12 different miRNA clusters, associated to specific groups of patients. The identified miRNAs were deregulated in breast tumours compared to healthy controls. Our approach has shown the association between specific sub-class of tumour samples having the same immuno-histo-chemical and/or histological features. Biclusters have been validated by means of two online repositories, MetaMirClust database and UCSC Genome Browser, and using another biclustering algorithm.ConclusionsThe obtained results with biclustering algorithm aimed first of all to give a contribute in the differential expression analysis in a cohort of BC patients and secondly to support the potential role that these non-coding RNA molecules could play in the clinical practice, in terms of prognosis, evolution of tumour and treatment response.

BackgroundStudies on genomic sequences for classification and taxonomic identification have a leading role in the biomedical field and in the analysis of biodiversity. These studies are focusing on the so-called barcode genes, representing a well defined region of the whole genome. Recently, alignment-free techniques are gaining more importance because they are able to overcome the drawbacks of sequence alignment techniques. In this paper a new alignment-free method for DNA sequences clustering and classification is proposed. The method is based on k-mers representation and text mining techniques.MethodsThe presented method is based on Probabilistic Topic Modeling, a statistical technique originally proposed for text documents. Probabilistic topic models are able to find in a document corpus the topics (recurrent themes) characterizing classes of documents. This technique, applied on DNA sequences representing the documents, exploits the frequency of fixed-length k-mers and builds a generative model for a training group of sequences. This generative model, obtained through the Latent Dirichlet Allocation (LDA) algorithm, is then used to classify a large set of genomic sequences.Results and conclusionsWe performed classification of over 7000 16S DNA barcode sequences taken from Ribosomal Database Project (RDP) repository, training probabilistic topic models. The proposed method is compared to the RDP tool and Support Vector Machine (SVM) classification algorithm in a extensive set of trials using both complete sequences and short sequence snippets (from 400 bp to 25 bp). Our method reaches very similar results to RDP classifier and SVM for complete sequences. The most interesting results are obtained when short sequence snippets are considered. In these conditions the proposed method outperforms RDP and SVM with ultra short sequences and it exhibits a smooth decrease of performance, at every taxonomic level, when the sequence length is decreased.

BackgroundSeveral online databases provide a large amount of biomedical data of different biological entities. These resources are typically stored in systems implementing their own data model, user interface and query language. On the other hand, in many bioinformatics scenarios there is often the need to use more than one resource. The availability of a single bioinformatics platform that integrates many biological resources and services is, for those reasons a fundamental issue.DescriptionHere, we present BioGraph, a web application that allows to query, visualize and analyze biological data belonging to several online available sources. BioGraph is built upon our previously developed graph database called BioGraphDB, that integrates and stores heterogeneous biological resources and make them available by means of a common structure and a unique query language. BioGraph implements state-of-the-art technologies and provides pre-compiled bioinformatics scenarios, as well as the possibility to perform custom queries and obtaining an interactive and dynamic visualization of results.ConclusionWe present a case study about functional analysis of microRNA in breast cancer in order to demonstrate the functionalities of the system. BioGraph is freely available at http://biograph.pa.icar.cnr.it. Source files are available on GitHub at https://github.com/IcarPA-TBlab/BioGraph

Background Non-coding RNAs include different classes of molecules with regulatory functions. The most studied are microRNAs (miRNAs) that act directly inhibiting mRNA expression or protein translation through the interaction with a miRNAs-response element. Other RNA molecules participate in the complex network of gene regulation. They behave as competitive endogenous RNA (ceRNA), acting as natural miRNA sponges to inhibit miRNA functions and modulate the expression of RNA messenger (mRNA). It became evident that understanding the ceRNA–miRNA–mRNA crosstalk would increase the functional information across the transcriptome, contributing to identify new potential biomarkers for translational medicine. Results We present miRTissue ce, an improvement of our original miRTissue web service. By introducing a novel computational pipeline, miRTissue ce provides an easy way to search for ceRNA interactions in several cancer tissue types. Moreover it extends the functionalities of previous miRTissue release about miRNA-target interaction in order to provide a complete insight about miRNA mediated regulation processes. miRTissue ce is freely available at http://tblab.pa.icar.cnr.it/mirtissue.html. Conclusions The study of ceRNA networks and its dynamics in cancer tissue could be applied in many fields of translational biology, as the investigation of new cancer biomarker, both diagnostic and prognostic, and also in the investigation of new therapeutic strategies of intervention. In this scenario, miRTissue ce can offer a powerful instrument for the analysis and characterization of ceRNA-ceRNA interactions in different tissue types, representing a fundamental step in order to understand more complex regulation mechanisms.