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1.
PLoS Comput Biol ; 16(10): e1008338, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33079938

RESUMO

Over the past two decades, researchers have discovered a special form of alternative splicing that produces a circular form of RNA. Although these circular RNAs (circRNAs) have garnered considerable attention in the scientific community for their biogenesis and functions, the focus of current studies has been on the tissue-specific circRNAs that exist only in one tissue but not in other tissues or on the disease-specific circRNAs that exist in certain disease conditions, such as cancer, but not under normal conditions. This approach was conducted in the relative absence of methods that analyze a group of common circRNAs that exist in both conditions, but are more abundant in one condition relative to another (differentially expressed). Studies of differentially expressed circRNAs (DECs) between two conditions would serve as a significant first step in filling this void. Here, we introduce a novel computational tool, seekCRIT (seek for differentially expressed CircRNAs In Transcriptome), that identifies the DECs between two conditions from high-throughput sequencing data. Using rat retina RNA-seq data from ischemic and normal conditions, we show that over 74% of identifiable circRNAs are expressed in both conditions and over 40 circRNAs are differentially expressed between two conditions. We also obtain a high qPCR validation rate of 90% for DECs with a FDR of < 5%. Our results demonstrate that seekCRIT is a novel and efficient approach to detect DECs using rRNA depleted RNA-seq data. seekCRIT is freely downloadable at https://github.com/UofLBioinformatics/seekCRIT. The source code is licensed under the MIT License. seekCRIT is developed and tested on Linux CentOS-7.


Assuntos
Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA Circular , Análise de Sequência de RNA/métodos , Transcriptoma/genética , Animais , Biologia Computacional , Bases de Dados Genéticas , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Ratos , Software
2.
Bioinformatics ; 36(1): 73-80, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268128

RESUMO

MOTIVATION: Over the past two decades, a circular form of RNA (circular RNA), produced through alternative splicing, has become the focus of scientific studies due to its major role as a microRNA (miRNA) activity modulator and its association with various diseases including cancer. Therefore, the detection of circular RNAs is vital to understanding their biogenesis and purpose. Prediction of circular RNA can be achieved in three steps: distinguishing non-coding RNAs from protein coding gene transcripts, separating short and long non-coding RNAs and predicting circular RNAs from other long non-coding RNAs (lncRNAs). However, the available tools are less than 80 percent accurate for distinguishing circular RNAs from other lncRNAs due to difficulty of classification. Therefore, the availability of a more accurate and fast machine learning method for the identification of circular RNAs, which considers the specific features of circular RNA, is essential to the development of systematic annotation. RESULTS: Here we present an End-to-End deep learning framework, circDeep, to classify circular RNA from other lncRNA. circDeep fuses an RCM descriptor, ACNN-BLSTM sequence descriptor and a conservation descriptor into high level abstraction descriptors, where the shared representations across different modalities are integrated. The experiments show that circDeep is not only faster than existing tools but also performs at an unprecedented level of accuracy by achieving a 12 percent increase in accuracy over the other tools. AVAILABILITY AND IMPLEMENTATION: https://github.com/UofLBioinformatics/circDeep. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Biologia Computacional , Aprendizado Profundo , RNA Circular , RNA Longo não Codificante , Biologia Computacional/métodos , RNA Circular/classificação , RNA Circular/genética , RNA Longo não Codificante/genética , Reprodutibilidade dos Testes
3.
Bioinformatics ; 35(14): i269-i277, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31510640

RESUMO

MOTIVATION: Deep learning architectures have recently demonstrated their power in predicting DNA- and RNA-binding specificity. Existing methods fall into three classes: Some are based on convolutional neural networks (CNNs), others use recurrent neural networks (RNNs) and others rely on hybrid architectures combining CNNs and RNNs. However, based on existing studies the relative merit of the various architectures remains unclear. RESULTS: In this study we present a systematic exploration of deep learning architectures for predicting DNA- and RNA-binding specificity. For this purpose, we present deepRAM, an end-to-end deep learning tool that provides an implementation of a wide selection of architectures; its fully automatic model selection procedure allows us to perform a fair and unbiased comparison of deep learning architectures. We find that deeper more complex architectures provide a clear advantage with sufficient training data, and that hybrid CNN/RNN architectures outperform other methods in terms of accuracy. Our work provides guidelines that can assist the practitioner in choosing an appropriate network architecture, and provides insight on the difference between the models learned by convolutional and recurrent networks. In particular, we find that although recurrent networks improve model accuracy, this comes at the expense of a loss in the interpretability of the features learned by the model. AVAILABILITY AND IMPLEMENTATION: The source code for deepRAM is available at https://github.com/MedChaabane/deepRAM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Sequência de Bases , DNA , RNA , Sensibilidade e Especificidade
4.
ISA Trans ; 88: 1-11, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30545772

RESUMO

This paper investigates the sensor and actuator fault (SAF) estimations and the fault tolerant tracking control (FTTC) problem for uncertain systems represented by Takagi-Sugeno (T-S) fuzzy model affected by Unknown Bounded Disturbance (UBD). A robust descriptor adaptive observer based FTTC is firstly designed to simultaneously estimate the unmeasurable system states and SAF vectors and then to track reference trajectories. Sufficient design conditions are developed in terms of Linear Matrix Inequalities (LMIs). The gains of both observer and fault tolerant controller are computed by solving a set of LMI constraints in single step. Robustness against external disturbances is analysed using the H∞ performance index to attenuate its effect on the tracking error for bounded reference inputs. Finally, simulation results are illustrated by considering three types of actuator faults. Moreover, two comparisons are presented to show the mentioned process effectiveness.

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