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

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

i4mC-GRU: Identifying DNA N⁴-Methylcytosine sites in mouse genomes using bidirectional gated recurrent unit and sequence-embedded features

N4-methylcytosine (4mC) is one of the most common DNA methylation modifications found in both prokaryotic and eukaryotic genomes. Since the 4mC has various essential biological roles, determining its location helps reveal unexplored physiological and pathological pathways. In this study, we propose an effective computational method called i4mC-GRU using a gated recurrent unit and duplet sequence-embedded features to predict potential 4mC sites in mouse (Mus musculus) genomes. To fairly assess the performance of the model, we compared our method with several state-of-the-art methods using two different benchmark datasets. Our results showed that i4mC-GRU achieved area under the receiver operating characteristic curve values of 0.97 and 0.89 and area under the precision-recall curve values of 0.98 and 0.90 on the first and second benchmark datasets, respectively. Briefly, our method outperformed existing methods in predicting 4mC sites in mouse genomes. Also, we deployed i4mC-GRU as an online web server, supporting users in genomics studies

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

iPromoter-Seqvec: identifying promoters using bidirectional long short-term memory and sequence-embedded features

Background: Promoters, non-coding DNA sequences located at upstream regions of the transcription start site of genes/gene clusters, are essential regulatory elements for the initiation and regulation of transcriptional processes. Furthermore, identifying promoters in DNA sequences and genomes significantly contributes to discovering entire structures of genes of interest. Therefore, exploration of promoter regions is one of the most imperative topics in molecular genetics and biology. Besides experimental techniques, computational methods have been developed to predict promoters. In this study, we propose iPromoter-Seqvec – an efficient computational model to predict TATA and non-TATA promoters in human and mouse genomes using bidirectional long short-term memory neural networks in combination with sequence-embedded features extracted from input sequences. The promoter and non-promoter sequences were retrieved from the Eukaryotic Promoter database and then were refined to create four benchmark datasets. Results: The area under the receiver operating characteristic curve (AUCROC) and the area under the precision-recall curve (AUCPR) were used as two key metrics to evaluate model performance. Results on independent test sets showed that iPromoter-Seqvec outperformed other state-of-the-art methods with AUCROC values ranging from 0.85 to 0.99 and AUCPR values ranging from 0.86 to 0.99. Models predicting TATA promoters in both species had slightly higher predictive power compared to those predicting non-TATA promoters. With a novel idea of constructing artificial non-promoter sequences based on promoter sequences, our models were able to learn highly specific characteristics discriminating promoters from non-promoters to improve predictive efficiency. Conclusions: iPromoter-Seqvec is a stable and robust model for predicting both TATA and non-TATA promoters in human and mouse genomes. Our proposed method was also deployed as an online web server with a user-friendly interface to support research communities. Links to our source codes and web server are available at https://github.com/mldlproject/2022-iPromoter-Seqvec

Predicting Drug-Induced Liver Injury using Convolutional Neural Network and Molecular Fingerprint-embedded features

© 2020 American Chemical Society. As a critical issue in drug development and postmarketing safety surveillance, drug-induced liver injury (DILI) leads to failures in clinical trials as well as retractions of on-market approved drugs. Therefore, it is important to identify DILI compounds in the early-stages through in silico and in vivo studies. It is difficult using conventional safety testing methods, since the predictive power of most of the existing frameworks is insufficiently effective to address this pharmacological issue. In our study, we employ a natural language processing (NLP) inspired computational framework using convolutional neural networks and molecular fingerprint-embedded features. Our development set and independent test set have 1597 and 322 compounds, respectively. These samples were collected from previous studies and matched with established chemical databases for structural validity. Our study comes up with an average accuracy of 0.89, Matthews's correlation coefficient (MCC) of 0.80, and an AUC of 0.96. Our results show a significant improvement in the AUC values compared to the recent best model with a boost of 6.67%, from 0.90 to 0.96. Also, based on our findings, molecular fingerprint-embedded featurizer is an effective molecular representation for future biological and biochemical studies besides the application of classic molecular fingerprints

Predicting Drug-Induced Liver Injury Using Convolutional Neural Network and Molecular Fingerprint-Embedded Features

© 2020 American Chemical Society. As a critical issue in drug development and postmarketing safety surveillance, drug-induced liver injury (DILI) leads to failures in clinical trials as well as retractions of on-market approved drugs. Therefore, it is important to identify DILI compounds in the early-stages through in silico and in vivo studies. It is difficult using conventional safety testing methods, since the predictive power of most of the existing frameworks is insufficiently effective to address this pharmacological issue. In our study, we employ a natural language processing (NLP) inspired computational framework using convolutional neural networks and molecular fingerprint-embedded features. Our development set and independent test set have 1597 and 322 compounds, respectively. These samples were collected from previous studies and matched with established chemical databases for structural validity. Our study comes up with an average accuracy of 0.89, Matthews's correlation coefficient (MCC) of 0.80, and an AUC of 0.96. Our results show a significant improvement in the AUC values compared to the recent best model with a boost of 6.67%, from 0.90 to 0.96. Also, based on our findings, molecular fingerprint-embedded featurizer is an effective molecular representation for future biological and biochemical studies besides the application of classic molecular fingerprints