PyFeat: a python - based effective feature generation tool for DNA, RNA, and protein sequences

Extracting useful feature set which contains significant discriminatory information is a critical step in effectively presenting sequence data to predict structural, functional, interaction and expression of proteins, DNAs, and RNAs. Also, being able to filter features with significant information and avoid sparsity in the extracted features require the employment of efficient feature selection techniques. Here we present PyFeat as a practical and easy to use toolkit implemented in Python for extracting various features from proteins, DNAs, and RNAs. To build PyFeat we mainly focused on extracting features that capture information about the interaction of neighboring residues to be able to provide more local information. We then employ AdaBoost technique to select features with maximum discriminatory information. In this way, we can significantly reduce the number of extracted features and enable PyFeat to represent the combination of effective features from large neighboring residues. As a result, PyFeat is able to extract features from 13 different techniques and represent context free combination of effective features. The source code for PyFeat standalone toolkit and employed benchmarks with a comprehensive user manual explaining its system and workflow in a step by step manner are publicly available

MiREx: mRNA levels prediction from gene sequence and miRNA target knowledge

Messenger RNA (mRNA) has an essential role in the protein production process. Predicting mRNA expression levels accurately is crucial for understanding gene regulation, and various models (statistical and neural network-based) have been developed for this purpose. A few models predict mRNA expression levels from the DNA sequence, exploiting the DNA sequence and gene features (e.g., number of exons/introns, gene length). Other models include information about long-range interaction molecules (i.e., enhancers/silencers) and transcriptional regulators as predictive features, such as transcription factors (TFs) and small RNAs (e.g., microRNAs - miRNAs). Recently, a convolutional neural network (CNN) model, called Xpresso, has been proposed for mRNA expression level prediction leveraging the promoter sequence and mRNAs’ half-life features (gene features). To push forward the mRNA level prediction, we present miREx, a CNN-based tool that includes information about miRNA targets and expression levels in the model. Indeed, each miRNA can target specific genes, and the model exploits this information to guide the learning process. In detail, not all miRNAs are included, only a selected subset with the highest impact on the model. MiREx has been evaluated on four cancer primary sites from the genomics data commons (GDC) database: lung, kidney, breast, and corpus uteri. Results show that mRNA level prediction benefits from selected miRNA targets and expression information. Future model developments could include other transcriptional regulators or be trained with proteomics data to infer protein levels

Classifying Included and Excluded Exons in Exon Skipping Event Using Histone Modifications

Alternative splicing (AS) not only ensures the diversity of gene expression products, but also closely correlated with genetic diseases. Therefore, knowledge about regulatory mechanisms of AS will provide useful clues for understanding its biological functions. In the current study, a random forest based method was developed to classify included and excluded exons in exon skipping event. In this method, the samples in the dataset were encoded by using optimal histone modification features which were optimized by using the Maximum Relevance Maximum Distance (MRMD) feature selection technique. The proposed method obtained an accuracy of 72.91% in 10-fold cross validation test and outperformed existing methods. Meanwhile, we also systematically analyzed the distribution of histone modifications between included and excluded exons and discovered their preference in both kinds of exons, which might provide insights into researches on the regulatory mechanisms of alternative splicing

iBitter-Fuse: A Novel Sequence-Based Bitter Peptide Predictor by Fusing Multi-View Features.

Accurate identification of bitter peptides is of great importance for better understanding their biochemical and biophysical properties. To date, machine learning-based methods have become effective approaches for providing a good avenue for identifying potential bitter peptides from large-scale protein datasets. Although few machine learning-based predictors have been developed for identifying the bitterness of peptides, their prediction performances could be improved. In this study, we developed a new predictor (named iBitter-Fuse) for achieving more accurate identification of bitter peptides. In the proposed iBitter-Fuse, we have integrated a variety of feature encoding schemes for providing sufficient information from different aspects, namely consisting of compositional information and physicochemical properties. To enhance the predictive performance, the customized genetic algorithm utilizing self-assessment-report (GA-SAR) was employed for identifying informative features followed by inputting optimal ones into a support vector machine (SVM)-based classifier for developing the final model (iBitter-Fuse). Benchmarking experiments based on both 10-fold cross-validation and independent tests indicated that the iBitter-Fuse was able to achieve more accurate performance as compared to state-of-the-art methods. To facilitate the high-throughput identification of bitter peptides, the iBitter-Fuse web server was established and made freely available online. It is anticipated that the iBitter-Fuse will be a useful tool for aiding the discovery and de novo design of bitter peptides

A Linear Regression Predictor for Identifying N 6 -Methyladenosine Sites Using Frequent Gapped K-mer Pattern

N6-methyladenosine (m 6 A) is one of the most common and abundant modifications in RNA, which is related to many biological processes in humans. Abnormal RNA modifications are often associated with a series of diseases, including tumors, neurogenic diseases, and embryonic retardation. Therefore, identifying m 6 A sites is of paramount importance in the post-genomic age. Although many lab-based methods have been proposed to annotate m 6 A sites, they are time consuming and cost ineffective. In view of the drawbacks of the intrinsic methods in RNA sequence recognition, computational methods are suggested as a supplement to identify m 6 A sites. In this study, we develop a novel feature extraction algorithm based on the frequent gapped k-mer pattern (FGKP) and apply the linear regression to construct the prediction model. The new predictor is used to identify m 6 A sites in the Saccharomyces cerevisiae database. It has been shown by the 10-fold cross-validation that the performance is better than that of recent methods. Comparative results indicate that our model has great potential to become a useful and effective tool for genome analysis and gain more insights for locating m 6 A sites

A Linear Regression Predictor for Identifying N6-Methyladenosine Sites Using Frequent Gapped K-mer Pattern.

N6-methyladenosine (m6A) is one of the most common and abundant modifications in RNA, which is related to many biological processes in humans. Abnormal RNA modifications are often associated with a series of diseases, including tumors, neurogenic diseases, and embryonic retardation. Therefore, identifying m6A sites is of paramount importance in the post-genomic age. Although many lab-based methods have been proposed to annotate m6A sites, they are time consuming and cost ineffective. In view of the drawbacks of the intrinsic methods in RNA sequence recognition, computational methods are suggested as a supplement to identify m6A sites. In this study, we develop a novel feature extraction algorithm based on the frequent gapped k-mer pattern (FGKP) and apply the linear regression to construct the prediction model. The new predictor is used to identify m6A sites in the Saccharomyces cerevisiae database. It has been shown by the 10-fold cross-validation that the performance is better than that of recent methods. Comparative results indicate that our model has great potential to become a useful and effective tool for genome analysis and gain more insights for locating m6A sites

DeePromoter: Robust Promoter Predictor Using Deep Learning

The promoter region is located near the transcription start sites and regulates transcription initiation of the gene by controlling the binding of RNA polymerase. Thus, promoter region recognition is an important area of interest in the field of bioinformatics. Numerous tools for promoter prediction were proposed. However, the reliability of these tools still needs to be improved. In this work, we propose a robust deep learning model, called DeePromoter, to analyze the characteristics of the short eukaryotic promoter sequences, and accurately recognize the human and mouse promoter sequences. DeePromoter combines a convolutional neural network (CNN) and a long short-term memory (LSTM). Additionally, instead of using non-promoter regions of the genome as a negative set, we derive a more challenging negative set from the promoter sequences. The proposed negative set reconstruction method improves the discrimination ability and significantly reduces the number of false positive predictions. Consequently, DeePromoter outperforms the previously proposed promoter prediction tools. In addition, a web-server for promoter prediction is developed based on the proposed methods and made available at https://home.jbnu.ac.kr/NSCL/deepromoter.htm

Identification of Antioxidant Proteins With Deep Learning From Sequence Information

Antioxidant proteins have been found closely linked to disease control for its ability to eliminate excess free radicals. Because of its medicinal value, the study of identifying antioxidant proteins is on the upsurge. Many machine-learning classifiers have performed poorly owing to the nonlinear and unbalanced nature of biological data. Recently, deep learning techniques showed advantages over many state-of-the-art machine learning methods in various fields. In this study, a deep learning based classifier was proposed to identify antioxidant proteins based on mixed g-gap dipeptide composition feature vector. The classifier employed deep autoencoder to extract nonlinear representation from raw input. The t-Distributed Stochastic Neighbor Embedding (t-SNE) was used for dimensionality reduction. Support vector machine was finally performed for classification. The classifier achieved F1 score of 0.8842 and MCC of 0.7409 in 10-fold cross validation. Experimental results show that our proposed method outperformed the traditional machine learning methods and could be a promising tool for antioxidant protein identification. For the convenience of others' scientific research, we have developed a user-friendly web server called IDAod for antioxidant protein identification, which can be accessed freely at http://bigroup.uestc.edu.cn/IDAod/

PIP-EL: A New Ensemble Learning Method for Improved Proinflammatory Peptide Predictions

Proinflammatory cytokines have the capacity to increase inflammatory reaction and play a central role in first line of defence against invading pathogens. Proinflammatory inducing peptides (PIPs) have been used as an antineoplastic agent, an antibacterial agent and a vaccine in immunization therapies. Due to the advancement in sequence technologies that resulted an avalanche of protein sequence data. Therefore, it is necessary to develop an automated computational method to enable fast and accurate identification of novel PIPs within the vast number of candidate proteins and peptides. To address this, we proposed a new predictor, PIP-EL, for predicting PIPs using the strategy of ensemble learning (EL). Our benchmarking dataset is imbalanced. Thus, we applied a random under-sampling technique to generate 10 balanced models for each composition. Technically, PIP-EL is the fusion of 50 independent random forest (RF) models, where each of the five different compositions, including amino acid, dipeptide, composition–transition–distribution, physicochemical properties, and amino acid index contains 10 RF models. PIP-EL achieves the Matthews’ correlation coefficient (MCC) of 0.435 in a 5-fold cross-validation test, which is ~2–5% higher than that of the individual classifiers and hybrid feature-based classifier. Furthermore, we evaluate the performance of PIP-EL on the independent dataset, showing that our method outperforms the existing method and two different machine learning methods developed in this study, with an MCC of 0.454. These results indicate that PIP-EL will be a useful tool for predicting PIPs and for researchers working in the field of peptide therapeutics and immunotherapy. The user-friendly web server, PIP-EL, is freely accessible.