M6AMRFS: Robust Prediction of N6-Methyladenosine Sites With Sequence-Based Features in Multiple Species

As one of the well-studied RNA methylation modifications, N6-methyladenosine (m6A) plays important roles in various biological progresses, such as RNA splicing and degradation, etc. Identification of m6A sites is fundamentally important for better understanding of their functional mechanisms. Recently, machine learning based prediction methods have emerged as an effective approach for fast and accurate identification of m6A sites. In this paper, we proposed “M6AMRFS”, a new machine learning based predictor for the identification of m6A sites. In this predictor, we exploited a new feature representation algorithm to encode RNA sequences with two feature descriptors (dinucleotide binary encoding and Local position-specific dinucleotide frequency), and used the F-score algorithm combined with SFS (Sequential Forward Search) to enhance the feature representation ability. To predict m6A sites, we employed the eXtreme Gradient Boosting (XGBoost) algorithm to build a predictive model. Benchmarking results showed that the proposed predictor is competitive with the state-of-the art predictors. Importantly, robust predictions for multiple species by our predictor demonstrate that our predictive models have strong generalization ability. To the best of our knowledge, M6AMRFS is the first tool that can be used for the identification of m6A sites in multiple species. To facilitate the use of our predictor, we have established a user-friendly webserver with the implementation of M6AMRFS, which is currently available in http://server.malab.cn/M6AMRFS/. We anticipate that it will be a useful tool for the relevant research of m6A sites

k-Skip-n-Gram-RF: A Random Forest Based Method for Alzheimer's Disease Protein Identification

In this paper, a computational method based on machine learning technique for identifying Alzheimer's disease genes is proposed. Compared with most existing machine learning based methods, existing methods predict Alzheimer's disease genes by using structural magnetic resonance imaging (MRI) technique. Most methods have attained acceptable results, but the cost is expensive and time consuming. Thus, we proposed a computational method for identifying Alzheimer disease genes by use of the sequence information of proteins, and classify the feature vectors by random forest. In the proposed method, the gene protein information is extracted by adaptive k-skip-n-gram features. The proposed method can attain the accuracy to 85.5% on the selected UniProt dataset, which has been demonstrated by the experimental results

Diagnosis of Brain Diseases via Multi-Scale Time-Series Model

The functional magnetic resonance imaging (fMRI) data and brain network analysis have been widely applied to automated diagnosis of neural diseases or brain diseases. The fMRI time series data not only contains specific numerical information, but also involves rich dynamic temporal information, those previous graph theory approaches focus on local topology structure and lose contextual information and global fluctuation information. Here, we propose a novel multi-scale functional connectivity for identifying the brain disease via fMRI data. We calculate the discrete probability distribution of co-activity between different brain regions with various intervals. Also, we consider nonsynchronous information under different time dimensions, for analyzing the contextual information in the fMRI data. Therefore, our proposed method can be applied to more disease diagnosis and other fMRI data, particularly automated diagnosis of neural diseases or brain diseases. Finally, we adopt Support Vector Machine (SVM) on our proposed time-series features, which can be applied to do the brain disease classification and even deal with all time-series data. Experimental results verify the effectiveness of our proposed method compared with other outstanding approaches on Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset and Major Depressive Disorder (MDD) dataset. Therefore, we provide an efficient system via a novel perspective to study brain networks

Exposing the Causal Effect of Body Mass Index on the Risk of Type 2 Diabetes Mellitus: A Mendelian Randomization Study

Introduction: High body mass index (BMI) is a positive associated phenotype of type 2 diabetes mellitus (T2DM). Abundant studies have observed this from a clinical perspective. Since the rapid increase in a large number of genetic variants from the genome-wide association studies (GWAS), common SNPs of BMI and T2DM were identified as the genetic basis for understanding their associations. Currently, their causality is beginning to blur.Materials and Methods: To classify it, a Mendelian randomisation (MR), using genetic instrumental variables (IVs) to explore the causality of intermediate phenotype and disease, was utilized here to test the effect of BMI on the risk of T2DM. In this article, MR was carried out on GWAS data using 52 independent BMI SNPs as IVs. The pooled odds ratio (OR) of these SNPs was calculated using inverse-variance weighted method for the assessment of 5 kg/m2 higher BMI on the risk of T2DM. The leave-one-out validation was conducted to identify the effect of individual SNPs. MR-Egger regression was utilized to detect potential pleiotropic bias of variants.Results: We obtained the high OR (1.470; 95% CI 1.170 to 1.847; P = 0.001), low intercept (0.004, P = 0.661), and small fluctuation of ORs {from -0.039 [(1.412 – 1.470) / 1.470)] to 0.075 [(1.568– 1.470) / 1.470)] in leave-one-out validation.Conclusion: We validate the causal effect of high BMI on the risk of T2DM. The low intercept shows no pleiotropic bias of IVs. The small alterations of ORs activated by removing individual SNPs showed no single SNP drives our estimate

Gradient Boosting Decision Tree-Based Method for Predicting Interactions Between Target Genes and Drugs

Determining the target genes that interact with drugs—drug–target interactions—plays an important role in drug discovery. Identification of drug–target interactions through biological experiments is time consuming, laborious, and costly. Therefore, using computational approaches to predict candidate targets is a good way to reduce the cost of wet-lab experiments. However, the known interactions (positive samples) and the unknown interactions (negative samples) display a serious class imbalance, which has an adverse effect on the accuracy of the prediction results. To mitigate the impact of class imbalance and completely exploit the negative samples, we proposed a new method, named DTIGBDT, based on gradient boosting decision trees, for predicting candidate drug–target interactions. We constructed a drug–target heterogeneous network that contains the drug similarities based on the chemical structures of drugs, the target similarities based on target sequences, and the known drug–target interactions. The topological information of the network was captured by random walks to update the similarities between drugs or targets. The paths between drugs and targets could be divided into multiple categories, and the features of each category of paths were extracted. We constructed a prediction model based on gradient boosting decision trees. The model establishes multiple decision trees with the extracted features and obtains the interaction scores between drugs and targets. DTIGBDT is a method of ensemble learning, and it effectively reduces the impact of class imbalance. The experimental results indicate that DTIGBDT outperforms several state-of-the-art methods for drug–target interaction prediction. In addition, case studies on Quetiapine, Clozapine, Olanzapine, Aripiprazole, and Ziprasidone demonstrate the ability of DTIGBDT to discover potential drug–target interactions

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

Meta-Path Methods for Prioritizing Candidate Disease miRNAs.

MicroRNAs (miRNAs) play critical roles in regulating gene expression at post-transcriptional levels. Numerous experimental studies indicate that alterations and dysregulations in miRNAs are associated with important complex diseases, especially cancers. Predicting potential miRNA-disease association is beneficial not only to explore the pathogenesis of diseases, but also to understand biological processes. In this work, we propose two methods that can effectively predict potential miRNA-disease associations using our reconstructed miRNA and disease similarity networks, which are based on the latest experimental data. We reconstruct a miRNA functional similarity network using the following biological information: the miRNA family information, miRNA cluster information, experimentally valid miRNA-target association and disease-miRNA information. We also reconstruct a disease similarity network using disease functional information and disease semantic information. We present Katz with specific weights and Katz with machine learning, on the comprehensive heterogeneous network. These methods, which achieve corresponding AUC values of 0.897 and 0.919, exhibit performance superior to the existing methods. Comprehensive data networks and reasonable considerations guarantee the high performance of our methods. Contrary to several methods, which cannot work in such situations, the proposed methods also predict associations for diseases without any known related miRNAs. A web service for the download and prediction of relationships between diseases and miRNAs is available at http://lab.malab.cn/soft/MDPredict/