IProDNA-CapsNet: Identifying protein-DNA binding residues using capsule neural networks

© 2019 The Author(s). Background: Since protein-DNA interactions are highly essential to diverse biological events, accurately positioning the location of the DNA-binding residues is necessary. This biological issue, however, is currently a challenging task in the age of post-genomic where data on protein sequences have expanded very fast. In this study, we propose iProDNA-CapsNet - a new prediction model identifying protein-DNA binding residues using an ensemble of capsule neural networks (CapsNets) on position specific scoring matrix (PSMM) profiles. The use of CapsNets promises an innovative approach to determine the location of DNA-binding residues. In this study, the benchmark datasets introduced by Hu et al. (2017), i.e., PDNA-543 and PDNA-TEST, were used to train and evaluate the model, respectively. To fairly assess the model performance, comparative analysis between iProDNA-CapsNet and existing state-of-the-art methods was done. Results: Under the decision threshold corresponding to false positive rate (FPR) ≈ 5%, the accuracy, sensitivity, precision, and Matthews's correlation coefficient (MCC) of our model is increased by about 2.0%, 2.0%, 14.0%, and 5.0% with respect to TargetDNA (Hu et al., 2017) and 1.0%, 75.0%, 45.0%, and 77.0% with respect to BindN+ (Wang et al., 2010), respectively. With regards to other methods not reporting their threshold settings, iProDNA-CapsNet also shows a significant improvement in performance based on most of the evaluation metrics. Even with different patterns of change among the models, iProDNA-CapsNets remains to be the best model having top performance in most of the metrics, especially MCC which is boosted from about 8.0% to 220.0%. Conclusions: According to all evaluation metrics under various decision thresholds, iProDNA-CapsNet shows better performance compared to the two current best models (BindN and TargetDNA). Our proposed approach also shows that CapsNet can potentially be used and adopted in other biological applications

Classification of adaptor proteins using recurrent neural networks and PSSM profiles

© 2019 The Author(s). Background: Adaptor proteins are carrier proteins that play a crucial role in signal transduction. They commonly consist of several modular domains, each having its own binding activity and operating by forming complexes with other intracellular-signaling molecules. Many studies determined that the adaptor proteins had been implicated in a variety of human diseases. Therefore, creating a precise model to predict the function of adaptor proteins is one of the vital tasks in bioinformatics and computational biology. Few computational biology studies have been conducted to predict the protein functions, and in most of those studies, position specific scoring matrix (PSSM) profiles had been used as the features to be fed into the neural networks. However, the neural networks could not reach the optimal result because the sequential information in PSSMs has been lost. This study proposes an innovative approach by incorporating recurrent neural networks (RNNs) and PSSM profiles to resolve this problem. Results: Compared to other state-of-the-art methods which had been applied successfully in other problems, our method achieves enhancement in all of the common measurement metrics. The area under the receiver operating characteristic curve (AUC) metric in prediction of adaptor proteins in the cross-validation and independent datasets are 0.893 and 0.853, respectively. Conclusions: This study opens a research path that can promote the use of RNNs and PSSM profiles in bioinformatics and computational biology. Our approach is reproducible by scientists that aim to improve the performance results of different protein function prediction problems. Our source code and datasets are available at https://github.com/ngphubinh/adaptors

IPseU-NCP: Identifying RNA pseudouridine sites using random forest and NCP-encoded features

© 2019 Nguyen-Vo et al. Background: Pseudouridine modification is most commonly found among various kinds of RNA modification occurred in both prokaryotes and eukaryotes. This biochemical event has been proved to occur in multiple types of RNAs, including rRNA, mRNA, tRNA, and nuclear/nucleolar RNA. Hence, gaining a holistic understanding of pseudouridine modification can contribute to the development of drug discovery and gene therapies. Although some laboratory techniques have come up with moderately good outcomes in pseudouridine identification, they are costly and required skilled work experience. We propose iPseU-NCP - an efficient computational framework to predict pseudouridine sites using the Random Forest (RF) algorithm combined with nucleotide chemical properties (NCP) generated from RNA sequences. The benchmark dataset collected from Chen et al. (2016) was used to develop iPseU-NCP and fairly compare its performances with other methods. Results: Under the same experimental settings, comparing with three state-of-the-art methods including iPseU-CNN, PseUI, and iRNA-PseU, the Matthew's correlation coefficient (MCC) of our model increased by about 20.0%, 55.0%, and 109.0% when tested on the H. sapiens (H_200) dataset and by about 6.5%, 35.0%, and 150.0% when tested on the S. cerevisiae (S_200) dataset, respectively. This significant growth in MCC is very important since it ensures the stability and performance of our model. With those two independent test datasets, our model also presented higher accuracy with a success rate boosted by 7.0%, 13.0%, and 20.0% and 2.0%, 9.5%, and 25.0% when compared to iPseU-CNN, PseUI, and iRNA-PseU, respectively. For majority of other evaluation metrics, iPseU-NCP demonstrated superior performance as well. Conclusions: iPseU-NCP combining the RF and NPC-encoded features showed better performances than other existing state-of-the-art methods in the identification of pseudouridine sites. This also shows an optimistic view in addressing biological issues related to human diseases

IEnhancer-ECNN: Identifying enhancers and their strength using ensembles of convolutional neural networks

© 2019 The Author(s). Background: Enhancers are non-coding DNA fragments which are crucial in gene regulation (e.g. transcription and translation). Having high locational variation and free scattering in 98% of non-encoding genomes, enhancer identification is, therefore, more complicated than other genetic factors. To address this biological issue, several in silico studies have been done to identify and classify enhancer sequences among a myriad of DNA sequences using computational advances. Although recent studies have come up with improved performance, shortfalls in these learning models still remain. To overcome limitations of existing learning models, we introduce iEnhancer-ECNN, an efficient prediction framework using one-hot encoding and k-mers for data transformation and ensembles of convolutional neural networks for model construction, to identify enhancers and classify their strength. The benchmark dataset from Liu et al.'s study was used to develop and evaluate the ensemble models. A comparative analysis between iEnhancer-ECNN and existing state-of-the-art methods was done to fairly assess the model performance. Results: Our experimental results demonstrates that iEnhancer-ECNN has better performance compared to other state-of-the-art methods using the same dataset. The accuracy of the ensemble model for enhancer identification (layer 1) and enhancer classification (layer 2) are 0.769 and 0.678, respectively. Compared to other related studies, improvements in the Area Under the Receiver Operating Characteristic Curve (AUC), sensitivity, and Matthews's correlation coefficient (MCC) of our models are remarkable, especially for the model of layer 2 with about 11.0%, 46.5%, and 65.0%, respectively. Conclusions: iEnhancer-ECNN outperforms other previously proposed methods with significant improvement in most of the evaluation metrics. Strong growths in the MCC of both layers are highly meaningful in assuring the stability of our models