lncRNA-protein Interaction Prediction Research Articles

Cross-domain contrastive graph neural network for lncRNA–protein interaction prediction

Identifying lncRNA–protein interactions (LPIs) is an important biomedical task, facilitating the comprehension of the biological functions and mechanisms of lncRNAs. Many computational methods have been developed for this task, especially graph neural network (GNN)-based methods have attracted increasing attention. Typically, the LPI network involves two types of interaction domains: the interactive domain capturing the direct interaction information between lncRNAs and proteins, and the collaborative domain reflecting the collaboration information among lncRNAs or proteins. However, existing GNN-based methods only leverage one of them to obtain topological information, which cannot fully characterize lncRNAs and proteins, resulting in suboptimal node representations. Moreover, each domain contains task-irrelevant redundant information, posing a challenge in effectively integrating information from different domains. To address these issues, we propose a novel Cross-domain Contrastive Graph Neural Network (CCGNN) for predicting potential LPIs. CCGNN employs a multi-domain encoder that consists of an interactive domain encoder and two collaborative domain encoders to capture valuable information from each interaction domain. Subsequently, domain-adaptive fusion is designed to integrate information from different domains to acquire comprehensive node representations. Furthermore, cross-domain contrastive learning is devised to enrich the node representations, drawing inspiration from the information bottleneck principle by retaining as much task-relevant information as possible within each domain and minimizing mutual information between representations across different domains. Extensive experiments on four real-world datasets demonstrate the superiority of CCGNN over state-of-the-art methods, and a further case study and generalization analysis illustrate the effectiveness of CCGNN in the biomedical link prediction tasks.

LncRNA–protein interaction prediction with reweighted feature selection

LncRNA–protein interactions are ubiquitous in organisms and play a crucial role in a variety of biological processes and complex diseases. Many computational methods have been reported for lncRNA–protein interaction prediction. However, the experimental techniques to detect lncRNA–protein interactions are laborious and time-consuming. Therefore, to address this challenge, this paper proposes a reweighting boosting feature selection (RBFS) method model to select key features. Specially, a reweighted apporach can adjust the contribution of each observational samples to learning model fitting; let higher weights are given more influence samples than those with lower weights. Feature selection with boosting can efficiently rank to iterate over important features to obtain the optimal feature subset. Besides, in the experiments, the RBFS method is applied to the prediction of lncRNA–protein interactions. The experimental results demonstrate that our method achieves higher accuracy and less redundancy with fewer features.

BoT-Net: a lightweight bag of tricks-based neural network for efficient LncRNA–miRNA interaction prediction

Background and objective:Interactions of long non-coding ribonucleic acids (lncRNAs) with micro-ribonucleic acids (miRNAs) play an essential role in gene regulation, cellular metabolic, and pathological processes. Existing purely sequence based computational approaches lack robustness and efficiency mainly due to the high length variability of lncRNA sequences. Hence, the prime focus of the current study is to find optimal length trade-offs between highly flexible length lncRNA sequences.MethodThe paper at hand performs in-depth exploration of diverse copy padding, sequence truncation approaches, and presents a novel idea of utilizing only subregions of lncRNA sequences to generate fixed-length lncRNA sequences. Furthermore, it presents a novel bag of tricks-based deep learning approach “Bot-Net” which leverages a single layer long-short-term memory network regularized through DropConnect to capture higher order residue dependencies, pooling to retain most salient features, normalization to prevent exploding and vanishing gradient issues, learning rate decay, and dropout to regularize precise neural network for lncRNA–miRNA interaction prediction.ResultsBoT-Net outperforms the state-of-the-art lncRNA–miRNA interaction prediction approach by 2%, 8%, and 4% in terms of accuracy, specificity, and matthews correlation coefficient. Furthermore, a case study analysis indicates that BoT-Net also outperforms state-of-the-art lncRNA–protein interaction predictor on a benchmark dataset by accuracy of 10%, sensitivity of 19%, specificity of 6%, precision of 14%, and matthews correlation coefficient of 26%.ConclusionIn the benchmark lncRNA–miRNA interaction prediction dataset, the length of the lncRNA sequence varies from 213 residues to 22,743 residues and in the benchmark lncRNA–protein interaction prediction dataset, lncRNA sequences vary from 15 residues to 1504 residues. For such highly flexible length sequences, fixed length generation using copy padding introduces a significant level of bias which makes a large number of lncRNA sequences very much identical to each other and eventually derail classifier generalizeability. Empirical evaluation reveals that within 50 residues of only the starting region of long lncRNA sequences, a highly informative distribution for lncRNA–miRNA interaction prediction is contained, a crucial finding exploited by the proposed BoT-Net approach to optimize the lncRNA fixed length generation process.Availability:BoT-Net web server can be accessed at https://sds_genetic_analysis.opendfki.de/lncmiRNA/.Graphic

EnANNDeep: An Ensemble-based lncRNA-protein Interaction Prediction Framework with Adaptive k-Nearest Neighbor Classifier and Deep Models.

lncRNA-protein interactions (LPIs) prediction can deepen the understanding of many important biological processes. Artificial intelligence methods have reported many possible LPIs. However, most computational techniques were evaluated mainly on one dataset, which may produce prediction bias. More importantly, they were validated only under cross validation on lncRNA-protein pairs, and did not consider the performance under cross validations on lncRNAs and proteins, thus fail to search related proteins/lncRNAs for a new lncRNA/protein. Under an ensemble learning framework (EnANNDeep) composed of adaptive k-nearest neighbor classifier and Deep models, this study focuses on systematically finding underlying linkages between lncRNAs and proteins. First, five LPI-related datasets are arranged. Second, multiple source features are integrated to depict an lncRNA-protein pair. Third, adaptive k-nearest neighbor classifier, deep neural network, and deep forest are designed to score unknown lncRNA-protein pairs, respectively. Finally, interaction probabilities from the three predictors are integrated based on a soft voting technique. In comparing to five classical LPI identification models (SFPEL, PMDKN, CatBoost, PLIPCOM, and LPI-SKF) under fivefold cross validations on lncRNAs, proteins, and LPIs, EnANNDeep computes the best average AUCs of 0.8660, 0.8775, and 0.9166, respectively, and the best average AUPRs of 0.8545, 0.8595, and 0.9054, respectively, indicating its superior LPI prediction ability. Case study analyses indicate that SNHG10 may have dense linkage with Q15717. In the ensemble framework, adaptive k-nearest neighbor classifier can separately pick the most appropriate k for each query lncRNA-protein pair. More importantly, deep models including deep neural network and deep forest can effectively learn the representative features of lncRNAs and proteins.

LPI-EnEDT: an ensemble framework with extra tree and decision tree classifiers for imbalanced lncRNA-protein interaction data classification

BackgroundLong noncoding RNAs (lncRNAs) have dense linkages with various biological processes. Identifying interacting lncRNA-protein pairs contributes to understand the functions and mechanisms of lncRNAs. Wet experiments are costly and time-consuming. Most computational methods failed to observe the imbalanced characterize of lncRNA-protein interaction (LPI) data. More importantly, they were measured based on a unique dataset, which produced the prediction bias.ResultsIn this study, we develop an Ensemble framework (LPI-EnEDT) with Extra tree and Decision Tree classifiers to implement imbalanced LPI data classification. First, five LPI datasets are arranged. Second, lncRNAs and proteins are separately characterized based on Pyfeat and BioTriangle and concatenated as a vector to represent each lncRNA-protein pair. Finally, an ensemble framework with Extra tree and decision tree classifiers is developed to classify unlabeled lncRNA-protein pairs. The comparative experiments demonstrate that LPI-EnEDT outperforms four classical LPI prediction methods (LPI-BLS, LPI-CatBoost, LPI-SKF, and PLIPCOM) under cross validations on lncRNAs, proteins, and LPIs. The average AUC values on the five datasets are 0.8480, 0,7078, and 0.9066 under the three cross validations, respectively. The average AUPRs are 0.8175, 0.7265, and 0.8882, respectively. Case analyses suggest that there are underlying associations between HOTTIP and Q9Y6M1, NRON and Q15717.ConclusionsFusing diverse biological features of lncRNAs and proteins and exploiting an ensemble learning model with Extra tree and decision tree classifiers, this work focus on imbalanced LPI data classification as well as interaction information inference for a new lncRNA (or protein).

LPI-HyADBS: a hybrid framework for lncRNA-protein interaction prediction integrating feature selection and classification

BackgroundLong noncoding RNAs (lncRNAs) have dense linkages with a plethora of important cellular activities. lncRNAs exert functions by linking with corresponding RNA-binding proteins. Since experimental techniques to detect lncRNA-protein interactions (LPIs) are laborious and time-consuming, a few computational methods have been reported for LPI prediction. However, computation-based LPI identification methods have the following limitations: (1) Most methods were evaluated on a single dataset, and researchers may thus fail to measure their generalization ability. (2) The majority of methods were validated under cross validation on lncRNA-protein pairs, did not investigate the performance under other cross validations, especially for cross validation on independent lncRNAs and independent proteins. (3) lncRNAs and proteins have abundant biological information, how to select informative features need to further investigate.ResultsUnder a hybrid framework (LPI-HyADBS) integrating feature selection based on AdaBoost, and classification models including deep neural network (DNN), extreme gradient Boost (XGBoost), and SVM with a penalty Coefficient of misclassification (C-SVM), this work focuses on finding new LPIs. First, five datasets are arranged. Each dataset contains lncRNA sequences, protein sequences, and an LPI network. Second, biological features of lncRNAs and proteins are acquired based on Pyfeat. Third, the obtained features of lncRNAs and proteins are selected based on AdaBoost and concatenated to depict each LPI sample. Fourth, DNN, XGBoost, and C-SVM are used to classify lncRNA-protein pairs based on the concatenated features. Finally, a hybrid framework is developed to integrate the classification results from the above three classifiers. LPI-HyADBS is compared to six classical LPI prediction approaches (LPI-SKF, LPI-NRLMF, Capsule-LPI, LPI-CNNCP, LPLNP, and LPBNI) on five datasets under 5-fold cross validations on lncRNAs, proteins, lncRNA-protein pairs, and independent lncRNAs and independent proteins. The results show LPI-HyADBS has the best LPI prediction performance under four different cross validations. In particular, LPI-HyADBS obtains better classification ability than other six approaches under the constructed independent dataset. Case analyses suggest that there is relevance between ZNF667-AS1 and Q15717.ConclusionsIntegrating feature selection approach based on AdaBoost, three classification techniques including DNN, XGBoost, and C-SVM, this work develops a hybrid framework to identify new linkages between lncRNAs and proteins.

A Survey of Current Resources to Study lncRNA-Protein Interactions.

Phenotypes are driven by regulated gene expression, which in turn are mediated by complex interactions between diverse biological molecules. Protein–DNA interactions such as histone and transcription factor binding are well studied, along with RNA–RNA interactions in short RNA silencing of genes. In contrast, lncRNA-protein interaction (LPI) mechanisms are comparatively unknown, likely directed by the difficulties in studying LPI. However, LPI are emerging as key interactions in epigenetic mechanisms, playing a role in development and disease. Their importance is further highlighted by their conservation across kingdoms. Hence, interest in LPI research is increasing. We therefore review the current state of the art in lncRNA-protein interactions. We specifically surveyed recent computational methods and databases which researchers can exploit for LPI investigation. We discovered that algorithm development is heavily reliant on a few generic databases containing curated LPI information. Additionally, these databases house information at gene-level as opposed to transcript-level annotations. We show that early methods predict LPI using molecular docking, have limited scope and are slow, creating a data processing bottleneck. Recently, machine learning has become the strategy of choice in LPI prediction, likely due to the rapid growth in machine learning infrastructure and expertise. While many of these methods have notable limitations, machine learning is expected to be the basis of modern LPI prediction algorithms.

Prediction of lncRNA-Protein Interactions via the Multiple Information Integration.

The long non-coding RNA (lncRNA)–protein interaction plays an important role in the post-transcriptional gene regulation, such as RNA splicing, translation, signaling, and the development of complex diseases. The related research on the prediction of lncRNA–protein interaction relationship is beneficial in the excavation and the discovery of the mechanism of lncRNA function and action occurrence, which are important. Traditional experimental methods for detecting lncRNA–protein interactions are expensive and time-consuming. Therefore, computational methods provide many effective strategies to deal with this problem. In recent years, most computational methods only use the information of the lncRNA–lncRNA or the protein–protein similarity and cannot fully capture all features to identify their interactions. In this paper, we propose a novel computational model for the lncRNA–protein prediction on the basis of machine learning methods. First, a feature method is proposed for representing the information of the network topological properties of lncRNA and protein interactions. The basic composition feature information and evolutionary information based on protein, the lncRNA sequence feature information, and the lncRNA expression profile information are extracted. Finally, the above feature information is fused, and the optimized feature vector is used with the recursive feature elimination algorithm. The optimized feature vectors are input to the support vector machine (SVM) model. Experimental results show that the proposed method has good effectiveness and accuracy in the lncRNA–protein interaction prediction.

A deep learning model for plant lncRNA-protein interaction prediction with graph attention.

Long non-coding RNAs (lncRNAs) play a broad spectrum of distinctive regulatory roles through interactions with proteins. However, only a few plant lncRNAs have been experimentally characterized. We propose GPLPI, a graph representation learning method, to predict plant lncRNA-protein interaction (LPI) from sequence and structural information. GPLPI employs a generative model using long short-term memory (LSTM) with graph attention. Evolutionary features are extracted using frequency chaos game representation (FCGR). Manifold regularization and l2-norm are adopted to obtain discriminant feature representations and mitigate overfitting. The model captures locality preserving and reconstruction constraints that lead to better generalization ability. Finally, potential interactions between lncRNAs and proteins are predicted by integrating catboost and regularized Logistic regression based on L-BFGS optimization algorithm. The method is trained and tested on Arabidopsis thaliana and Zea mays datasets. GPLPI achieves accuracies of 85.76% and 91.97% respectively. The results show that our method consistently outperforms other state-of-the-art methods.

A comparison between long non-coding RNA repertoires of exosomes derived from naïve and cytokine-activated human mesenchymal stem cells

Background & Aim Mesenchymal stem cells (MSCs) are being used in the fields of regenerative medicine, especially in the treatment of musculoskeletal disorders, diabetes, autoimmune diseases, neuronal injury, and neurodegeneration. The therapeutic effects of MSCs are largely mediated by paracrine factors including exosomes, which are nanometer-sized membrane-bound vesicles with functions as mediators of cell-cell communication. Interestingly, the therapeutic potential of MSCs could be prompted by pro-inflammatory cytokines stimulation. The alternation of MSC-secreted immunomodulatory factors composition after cytokine treatment strengthen the modulation of exosomal regenerative nature. MSC-derived exosomes bypass the concern of pro-fibrogenic potential and the possibility of tumorigenicity upon in vivo transplantation of MSCs and could represent a novel cell-free therapeutics. However, the composition of exosomes, in particular long non-coding RNAs (lncRNAs), are not comprehensively investigated. In this study, we compared the expression level of long non-coding RNAs in exosomes derived from naive and cytokine-activated human adipose-derived MSCs. Methods, Results & Conclusion Human adipose-derived MSCs were incubated with or without TNF-α and IFN-γ in serum-free medium for 24 hrs, and the condition medium were harvested for exosome isolation and small RNA sequencing. Exosome isolation protocol is as previously described (Wu and Lee, Stem Cell Research & Therapy (2017) 8:117). Small RNAs in exosomes were sequenced by the Illumina HiSeq 2500 System (50SE). Twenty upregulated lncRNAs after cytokine treatment are selected for lncRNA-RNA and lncRNA-protein interaction prediction. Our results provide a reference dataset that can help to identify the therapeutic targets for future translational studies.

Recent Advances on the Semi-Supervised Learning for Long Non-Coding RNA-Protein Interactions Prediction: A Review.

In recent years, more and more evidence indicates that long non-coding RNA (lncRNA) plays a significant role in the development of complex biological processes, especially in RNA progressing, chromatin modification, and cell differentiation, as well as many other processes. Surprisingly, lncRNA has an inseparable relationship with human diseases such as cancer. Therefore, only by knowing more about the function of lncRNA can we better solve the problems of human diseases. However, lncRNAs need to bind to proteins to perform their biomedical functions. So we can reveal the lncRNA function by studying the relationship between lncRNA and protein. But due to the limitations of traditional experiments, researchers often use computational prediction models to predict lncRNA protein interactions. In this review, we summarize several computational models of the lncRNA protein interactions prediction base on semi-supervised learning during the past two years, and introduce their advantages and shortcomings briefly. Finally, the future research directions of lncRNA protein interaction prediction are pointed out.

Projection-Based Neighborhood Non-Negative Matrix Factorization for lncRNA-Protein Interaction Prediction.

Many long ncRNAs (lncRNA) make their effort by interacting with the corresponding RNA-binding proteins, and identifying the interactions between lncRNAs and proteins is important to understand the functions of lncRNA. Compared with the time-consuming and laborious experimental methods, more and more computational models are proposed to predict lncRNA-protein interactions. However, few models can effectively utilize the biological network topology of lncRNA (protein) and combine its sequence structure features, and most models cannot effectively predict new proteins (lncRNA) that do not interact with any lncRNA (proteins). In this study, we proposed a projection-based neighborhood non-negative matrix decomposition model (PMKDN) to predict potential lncRNA-protein interactions by integrating multiple biological features of lncRNAs (proteins). First, according to lncRNA (protein) sequences and lncRNA expression profile data, we extracted multiple features of lncRNA (protein). Second, based on protein GO ontology annotation, lncRNA sequences, lncRNA(protein) feature information, and modified lncRNA-protein interaction network, we calculated multiple similarities of lncRNA (protein), and fused them to obtain a more accurate lncRNA(protein) similarity network. Finally, combining the similarity and various feature information of lncRNA (protein), as well as the modified interaction network, we proposed a projection-based neighborhood non-negative matrix decomposition algorithm to predict the potential lncRNA-protein interactions. On two benchmark datasets, PMKDN showed better performance than other state-of-the-art methods for the prediction of new lncRNA-protein interactions, new lncRNAs, and new proteins. Case study further indicates that PMKDN can be used as an effective tool for lncRNA-protein interaction prediction.

A path-based computational model for long non-coding RNA-protein interaction prediction

Recently, lncRNAs have attracted accumulating attentions because more and more experimental researches have shown lncRNA can play critical roles in many biological processes. Predicting potential interactions between lncRNAs and proteins are key to understand the lncRNAs biological functions. But traditional biological experiments are expensive and time-consuming, network similarity methods provide a powerful solution to computationally predict lncRNA-protein interactions. In this work, a novel path-based lncRNA-protein interaction (PBLPI) prediction model is proposed by integrating protein semantic similarity, lncRNA functional similarity, known human lncRNA-protein interactions, and Gaussian interaction profile kernel similarity. PBLPI model utilizes three interlinked sub-graphs to construct a heterogeneous graph, and then infers potential lncRNA-protein interactions through depth-first search algorithm. Consequently, PBLPI achieves reliable performance in the frameworks of 5-fold cross validation (average AUC is 0.9244 and AUPR is 0.6478). In the case study, we use “Mus musculus” data to further validate the reliability of PBLPI method. It is anticipated that PBLPI would become a useful tool to identify potential lncRNA-protein interactions.

A Hybrid Prediction Method for Plant lncRNA-Protein Interaction.

Long non-protein-coding RNAs (lncRNAs) identification and analysis are pervasive in transcriptome studies due to their roles in biological processes. In particular, lncRNA-protein interaction has plausible relevance to gene expression regulation and in cellular processes such as pathogen resistance in plants. While lncRNA-protein interaction has been studied in animals, there has yet to be extensive research in plants. In this paper, we propose a novel plant lncRNA-protein interaction prediction method, namely PLRPIM, which combines deep learning and shallow machine learning methods. The selection of an optimal feature subset and subsequent efficient compression are significant challenges for deep learning models. The proposed method adopts k-mer and extracts high-level abstraction sequence-based features using stacked sparse autoencoder. Based on the extracted features, the fusion of random forest (RF) and light gradient boosting machine (LGBM) is used to build the prediction model. The performances are evaluated on Arabidopsis thaliana and Zea mays datasets. Results from experiments demonstrate PLRPIM’s superiority compared with other prediction tools on the two datasets. Based on 5-fold cross-validation, we obtain 89.98% and 93.44% accuracy, 0.954 and 0.982 AUC for Arabidopsis thaliana and Zea mays, respectively. PLRPIM predicts potential lncRNA-protein interaction pairs effectively, which can facilitate lncRNA related research including function prediction.

Long Noncoding RNA and Protein Interactions: From Experimental Results to Computational Models Based on Network Methods.

Non-coding RNAs with a length of more than 200 nucleotides are long non-coding RNAs (lncRNAs), which have gained tremendous attention in recent decades. Many studies have confirmed that lncRNAs have important influence in post-transcriptional gene regulation; for example, lncRNAs affect the stability and translation of splicing factor proteins. The mutations and malfunctions of lncRNAs are closely related to human disorders. As lncRNAs interact with a variety of proteins, predicting the interaction between lncRNAs and proteins is a significant way to depth exploration functions and enrich annotations of lncRNAs. Experimental approaches for lncRNA–protein interactions are expensive and time-consuming. Computational approaches to predict lncRNA–protein interactions can be grouped into two broad categories. The first category is based on sequence, structural information and physicochemical property. The second category is based on network method through fusing heterogeneous data to construct lncRNA related heterogeneous network. The network-based methods can capture the implicit feature information in the topological structure of related biological heterogeneous networks containing lncRNAs, which is often ignored by sequence-based methods. In this paper, we summarize and discuss the materials, interaction score calculation algorithms, advantages and disadvantages of state-of-the-art algorithms of lncRNA–protein interaction prediction based on network methods to assist researchers in selecting a suitable method for acquiring more dependable results. All the related different network data are also collected and processed in convenience of users, and are available at https://github.com/HAN-Siyu/APINet/.

Multivariate Information Fusion With Fast Kernel Learning to Kernel Ridge Regression in Predicting LncRNA-Protein Interactions.

Long non-coding RNAs (lncRNAs) constitute a large class of transcribed RNA molecules. They have a characteristic length of more than 200 nucleotides which do not encode proteins. They play an important role in regulating gene expression by interacting with the homologous RNA-binding proteins. Due to the laborious and time-consuming nature of wet experimental methods, more researchers should pay great attention to computational approaches for the prediction of lncRNA-protein interaction (LPI). An in-depth literature review in the state-of-the-art in silico investigations, leads to the conclusion that there is still room for improving the accuracy and velocity. This paper propose a novel method for identifying LPI by employing Kernel Ridge Regression, based on Fast Kernel Learning (LPI-FKLKRR). This approach, uses four distinct similarity measures for lncRNA and protein space, respectively. It is remarkable, that we extract Gene Ontology (GO) with proteins, in order to improve the quality of information in protein space. The process of heterogeneous kernels integration, applies Fast Kernel Learning (FastKL) to deal with weight optimization. The extrapolation model is obtained by gaining the ultimate prediction associations, after using Kernel Ridge Regression (KRR). Experimental outcomes show that the ability of modeling with LPI-FKLKRR has extraordinary performance compared with LPI prediction schemes. On benchmark dataset, it has been observed that the best Area Under Precision Recall Curve (AUPR) of 0.6950 is obtained by our proposed model LPI-FKLKRR, which outperforms the integrated LPLNP (AUPR: 0.4584), RWR (AUPR: 0.2827), CF (AUPR: 0.2357), LPIHN (AUPR: 0.2299), and LPBNI (AUPR: 0.3302). Also, combined with the experimental results of a case study on a novel dataset, it is anticipated that LPI-FKLKRR will be a useful tool for LPI prediction.

LPI-KTASLP: Prediction of LncRNA-Protein Interaction by Semi-Supervised Link Learning With Multivariate Information

Long non-coding RNA, also known as lncRNA, is a series of single-stranded polynucleotides (no less than 200 nucleotides each), consisting of non-protein coding transcripts. LncRNA plays a crucial role in regulating gene expression, during the transcriptional, post-transcriptional, and epigenetic processes. This is achieved by lncRNA interacts with the corresponding RNA-binding proteins. It has been drawn to a lot of attention that the reduction of the excessive laboratory cost and the increase in speed and accuracy gains benefits from the employment of computational intelligence in lncRNA-protein interaction (LPI) identification. Although numerous pertinent in silico studies of LPI prediction have been proposed, there is still room for enhancing the accuracy of the existing LPI prediction methods. In this paper, we have proposed a novel method for identifying LPI with kernel target alignment based on semi-supervised link prediction (LPI-KTASLP), which adopts multivariate information to predict lncRNAs-proteins interactions. To integrate the heterogeneous kernels, kernel target alignment has been applied to deal with kernel fusion. We have calculated the low-rank approximation matrices of lncRNA and protein, where eigendecomposition is used to reduce computing pressure. The prediction model has been obtained by producing the ultimate LPI prediction matrix. Experimental results show that the prediction ability of the LPI-KTASLP algorithm has surpassed many other LPI prediction schemes. Our method of lncRNA-protein interaction prediction has been evaluated on a standard benchmark dataset of LPIs. We have observed that the highest AUPR of 0.6148 is obtained by our proposed model (LPI-KTASLP). This is superior to the integrated LPLNP (AUPR: 0.4584), the RWR (AUPR: 0.2827), the CF (AUPR: 0.2357), the LPIHN (AUPR: 0.2299), and the LPBNI (AUPR: 0.3302). It is very encouraging that most of the LPI predictions have been confirmed to be close to relevant concentrations.

LncFinder: an integrated platform for long non-coding RNA identification utilizing sequence intrinsic composition, structural information and physicochemical property.

Discovering new long non-coding RNAs (lncRNAs) has been a fundamental step in lncRNA-related research. Nowadays, many machine learning-based tools have been developed for lncRNA identification. However, many methods predict lncRNAs using sequence-derived features alone, which tend to display unstable performances on different species. Moreover, the majority of tools cannot be re-trained or tailored by users and neither can the features be customized or integrated to meet researchers’ requirements. In this study, features extracted from sequence-intrinsic composition, secondary structure and physicochemical property are comprehensively reviewed and evaluated. An integrated platform named LncFinder is also developed to enhance the performance and promote the research of lncRNA identification. LncFinder includes a novel lncRNA predictor using the heterologous features we designed. Experimental results show that our method outperforms several state-of-the-art tools on multiple species with more robust and satisfactory results. Researchers can additionally employ LncFinder to extract various classic features, build classifier with numerous machine learning algorithms and evaluate classifier performance effectively and efficiently. LncFinder can reveal the properties of lncRNA and mRNA from various perspectives and further inspire lncRNA–protein interaction prediction and lncRNA evolution analysis. It is anticipated that LncFinder can significantly facilitate lncRNA-related research, especially for the poorly explored species. LncFinder is released as R package (https://CRAN.R-project.org/package=LncFinder). A web server (http://bmbl.sdstate.edu/lncfinder/) is also developed to maximize its availability.

IRWNRLPI: Integrating Random Walk and Neighborhood Regularized Logistic Matrix Factorization for lncRNA-Protein Interaction Prediction.

Long non-coding RNA (lncRNA) plays an important role in many important biological processes and has attracted widespread attention. Although the precise functions and mechanisms for most lncRNAs are still unknown, we are certain that lncRNAs usually perform their functions by interacting with the corresponding RNA- binding proteins. For example, lncRNA-protein interactions play an important role in post transcriptional gene regulation, such as splicing, translation, signaling, and advances in complex diseases. However, experimental verification of lncRNA-protein interactions prediction is time-consuming and laborious. In this work, we propose a computational method, named IRWNRLPI, to find the potential associations between lncRNAs and proteins. IRWNRLPI integrates two algorithms, random walk and neighborhood regularized logistic matrix factorization, which can optimize a lot more than using an algorithm alone. Moreover, the method is semi-supervised and does not require negative samples. Based on the leave-one-out cross validation, we obtain the AUC of 0.9150 and the AUPR of 0.7138, demonstrating its reliable performance. In addition, by means of case study in the “Mus musculus,” many lncRNA-protein interactions which are predicted by our method can be successfully confirmed by experiments. This suggests that IRWNRLPI will be a useful bioinformatics resource in biomedical research.

LncADeep: an ab initio lncRNA identification and functional annotation tool based on deep learning.

To characterize long non-coding RNAs (lncRNAs), both identifying and functionally annotating them are essential to be addressed. Moreover, a comprehensive construction for lncRNA annotation is desired to facilitate the research in the field. We present LncADeep, a novel lncRNA identification and functional annotation tool. For lncRNA identification, LncADeep integrates intrinsic and homology features into a deep belief network and constructs models targeting both full- and partial-length transcripts. For functional annotation, LncADeep predicts a lncRNA's interacting proteins based on deep neural networks, using both sequence and structure information. Furthermore, LncADeep integrates KEGG and Reactome pathway enrichment analysis and functional module detection with the predicted interacting proteins, and provides the enriched pathways and functional modules as functional annotations for lncRNAs. Test results show that LncADeep outperforms state-of-the-art tools, both for lncRNA identification and lncRNA-protein interaction prediction, and then presents a functional interpretation. We expect that LncADeep can contribute to identifying and annotating novel lncRNAs. LncADeep is freely available for academic use at http://cqb.pku.edu.cn/ZhuLab/lncadeep/ and https://github.com/cyang235/LncADeep/. Supplementary data are available at Bioinformatics online.