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

Screening potential lncRNA biomarkers for breast cancer and colorectal cancer combining random walk and logistic matrix factorization

Breast cancer and colorectal cancer are two of the most common malignant tumors worldwide. They cause the leading causes of cancer mortality. Many researches have demonstrated that long noncoding RNAs (lncRNAs) have close linkages with the occurrence and development of the two cancers. Therefore, it is essential to design an effective way to identify potential lncRNA biomarkers for them. In this study, we developed a computational method (LDA-RWLMF) by integrating random walk with restart and Logistic Matrix Factorization to investigate the roles of lncRNA biomarkers in the prognosis and diagnosis of the two cancers. We first fuse disease semantic and Gaussian association profile similarities and lncRNA functional and Gaussian association profile similarities. Second, we design a negative selection algorithm to extract negative LncRNA-Disease Associations (LDA) based on random walk. Third, we develop a logistic matrix factorization model to predict possible LDAs. We compare our proposed LDA-RWLMF method with four classical LDA prediction methods, that is, LNCSIM1, LNCSIM2, ILNCSIM, and IDSSIM. The results from 5-fold cross validation on the MNDR dataset show that LDA-RWLMF computes the best AUC value of 0.9312, outperforming the above four LDA prediction methods. Finally, we rank all lncRNA biomarkers for the two cancers after determining the performance of LDA-RWLMF, respectively. We find that 48 and 50 lncRNAs have the highest association scores with breast cancer and colorectal cancer among all lncRNAs known to associate with them on the MNDR dataset, respectively. We predict that lncRNAs HULC and HAR1A could be separately potential biomarkers for breast cancer and colorectal cancer and need to biomedical experimental validation

LPI-IBNRA: Long Non-coding RNA-Protein Interaction Prediction Based on Improved Bipartite Network Recommender Algorithm

According to the latest research, lncRNAs (long non-coding RNAs) play a broad and important role in various biological processes by interacting with proteins. However, identifying whether proteins interact with a specific lncRNA through biological experimental methods is difficult, costly, and time-consuming. Thus, many bioinformatics computational methods have been proposed to predict lncRNA-protein interactions. In this paper, we proposed a novel approach called Long non-coding RNA-Protein Interaction Prediction based on Improved Bipartite Network Recommender Algorithm (LPI-IBNRA). In the proposed method, we implemented a two-round resource allocation and eliminated the second-order correlations appropriately on the bipartite network. Experimental results illustrate that LPI-IBNRA outperforms five previous methods, with the AUC values of 0.8932 in leave-one-out cross validation (LOOCV) and 0.8819 ± 0.0052 in 10-fold cross validation, respectively. In addition, case studies on four lncRNAs were carried out to show the predictive power of LPI-IBNRA

Identification of RNA Oligonucleotide and Protein Interactions Using Term Frequency Inverse Document Frequency and Random Forest

The interaction between protein and Ribonucleic Acid (RNA) plays crucial roles in many biological aspects such as gene expression, posttranscriptional regulation, and protein synthesis. However, the experimental screening of protein-RNA binding affinity is laborious and time-consuming, there is a pressing desire of accurate and reliable computational approaches. In this study, we proposed a novel method to predict that interaction based on both sequences of protein and RNA. The Random Forest was trained and tested on a combination of benchmark datasets and the term frequency–inverse document frequency method combined with XgBoost algorithm was used to extract useful information from sequences. The performance of our method was very impressive, and the accuracy was as high as 94%, the Area Under the Curve of 0.98 and the Matthew Correlation Coefficient (MCC) of 0.90. All these high metrics, especially the MCC, show that our method is robust enough to keep its performance on unseen datasets

Discovering Cancer Subtypes via an Accurate Fusion Strategy on Multiple Profile Data

Discovering cancer subtypes is useful for guiding clinical treatment of multiple cancers. Progressive profile technologies for tissue have accumulated diverse types of data. Based on these types of expression data, various computational methods have been proposed to predict cancer subtypes. It is crucial to study how to better integrate these multiple profiles of data. In this paper, we collect multiple profiles of data for five cancers on The Cancer Genome Atlas (TCGA). Then, we construct three similarity kernels for all patients of the same cancer by gene expression, miRNA expression and isoform expression data. We also propose a novel unsupervised multiple kernel fusion method, Similarity Kernel Fusion (SKF), in order to integrate three similarity kernels into one combined kernel. Finally, we make use of spectral clustering on the integrated kernel to predict cancer subtypes. In the experimental results, the P-values from the Cox regression model and survival curve analysis can be used to evaluate the performance of predicted subtypes on three datasets. Our kernel fusion method, SKF, has outstanding performance compared with single kernel and other multiple kernel fusion strategies. It demonstrates that our method can accurately identify more accurate subtypes on various kinds of cancers. Our cancer subtype prediction method can identify essential genes and biomarkers for disease diagnosis and prognosis, and we also discuss the possible side effects of therapies and treatment

Application of Machine Learning in Microbiology

Microorganisms are ubiquitous and closely related to people’s daily lives. Since they were first discovered in the 19th century, researchers have shown great interest in microorganisms. People studied microorganisms through cultivation, but this method is expensive and time consuming. However, the cultivation method cannot keep a pace with the development of high-throughput sequencing technology. To deal with this problem, machine learning (ML) methods have been widely applied to the field of microbiology. Literature reviews have shown that ML can be used in many aspects of microbiology research, especially classification problems, and for exploring the interaction between microorganisms and the surrounding environment. In this study, we summarize the application of ML in microbiology

PredT4SE-Stack: Prediction of Bacterial Type IV Secreted Effectors From Protein Sequences Using a Stacked Ensemble Method

Gram-negative bacteria use various secretion systems to deliver their secreted effectors. Among them, type IV secretion system exists widely in a variety of bacterial species, and secretes type IV secreted effectors (T4SEs), which play vital roles in host-pathogen interactions. However, experimental approaches to identify T4SEs are time- and resource-consuming. In the present study, we aim to develop an in silico stacked ensemble method to predict whether a protein is an effector of type IV secretion system or not based on its sequence information. The protein sequences were encoded by the feature of position specific scoring matrix (PSSM)-composition by summing rows that correspond to the same amino acid residues in PSSM profiles. Based on the PSSM-composition features, we develop a stacked ensemble model PredT4SE-Stack to predict T4SEs, which utilized an ensemble of base-classifiers implemented by various machine learning algorithms, such as support vector machine, gradient boosting machine, and extremely randomized trees, to generate outputs for the meta-classifier in the classification system. Our results demonstrated that the framework of PredT4SE-Stack was a feasible and effective way to accurately identify T4SEs based on protein sequence information. The datasets and source code of PredT4SE-Stack are freely available at http://xbioinfo.sjtu.edu.cn/PredT4SE_Stack/index.php