PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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PubChem in 2021: new data content and improved web interfaces.

Motivation Graph embedding learning that aims to automatically learn low-dimensional node representations, has drawn increasing attention in recent years. To date, most recent graph embedding methods are evaluated on social and information networks and are not comprehensively studied on biomedical networks under systematic experiments and analyses. On the other hand, for a variety of biomedical network analysis tasks, traditional techniques such as matrix factorization (which can be seen as a type of graph embedding methods) have shown promising results, and hence there is a need to systematically evaluate the more recent graph embedding methods (e.g. random walk-based and neural network-based) in terms of their usability and potential to further the state-of-the-art. Results We select 11 representative graph embedding methods and conduct a systematic comparison on 3 important biomedical link prediction tasks: drug-disease association (DDA) prediction, drug-drug interaction (DDI) prediction, protein-protein interaction (PPI) prediction; and 2 node classification tasks: medical term semantic type classification, protein function prediction. Our experimental results demonstrate that the recent graph embedding methods achieve promising results and deserve more attention in the future biomedical graph analysis. Compared with three state-of-the-art methods for DDAs, DDIs and protein function predictions, the recent graph embedding methods achieve competitive performance without using any biological features and the learned embeddings can be treated as complementary representations for the biological features. By summarizing the experimental results, we provide general guidelines for properly selecting graph embedding methods and setting their hyper-parameters for different biomedical tasks. Availability and implementation As part of our contributions in the paper, we develop an easy-to-use Python package with detailed instructions, BioNEV, available at: https://github.com/xiangyue9607/BioNEV, including all source code and datasets, to facilitate studying various graph embedding methods on biomedical tasks. Supplementary information Supplementary data are available at Bioinformatics online.

Graph embedding on biomedical networks: methods, applications and evaluations.

Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available.Database URL: http://www.ensembl.org.

Database: The Journal of Biological Databases and Curation

Drug-disease associations provide important information for the drug discovery. Wet experiments that identify drug-disease associations are time-consuming and expensive. However, many drug-disease associations are still unobserved or unknown. The development of computational methods for predicting unobserved drug-disease associations is an important and urgent task. In this paper, we proposed a similarity constrained matrix factorization method for the drug-disease association prediction (SCMFDD), which makes use of known drug-disease associations, drug features and disease semantic information. SCMFDD projects the drug-disease association relationship into two low-rank spaces, which uncover latent features for drugs and diseases, and then introduces drug feature-based similarities and disease semantic similarity as constraints for drugs and diseases in low-rank spaces. Different from the classic matrix factorization technique, SCMFDD takes the biological context of the problem into account. In computational experiments, the proposed method can produce high-accuracy performances on benchmark datasets, and outperform existing state-of-the-art prediction methods when evaluated by five-fold cross validation and independent testing. We developed a user-friendly web server by using known associations collected from the CTD database, available at http://www.bioinfotech.cn/SCMFDD/
 . The case studies show that the server can find out novel associations, which are not included in the CTD database.

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Predicting drug-disease associations by using similarity constrained matrix factorization

N6-methyladenosine (m6A) modification is the most abundant RNA methylation modification and involves various biological processes, such as RNA splicing and degradation. Recent studies have demonstrated the feasibility of identifying m6A peaks using high-throughput sequencing techniques. However, such techniques cannot accurately identify specific methylated sites, which is important for a better understanding of m6A functions. In this study, we develop a novel machine learning-based predictor called M6APred-EL for the identification of m6A sites. To predict m6A sites accurately within genomic sequences, we trained an ensemble of three support vector machine classifiers that explore the position-specific information and physical chemical information from position-specific k-mer nucleotide propensity, physical-chemical properties, and ring-function-hydrogen-chemical properties. We examined and compared the performance of our predictor with other state-of-the-art methods of benchmarking datasets. Comparative results showed that the proposed M6APred-EL performed more accurately for m6A site identification. Moreover, a user-friendly web server that implements the proposed M6APred-EL is well established and is currently available at http://server.malab.cn/M6APred-EL/. It is expected to be a practical and effective tool for the investigation of m6A functional mechanisms.

M6APred-EL: A Sequence-Based Predictor for Identifying N6-methyladenosine Sites Using Ensemble Learning

LncRNA-protein interactions play important roles in post-transcriptional gene regulation, poly-adenylation, splicing and translation. Identification of lncRNA-protein interactions helps to understand lncRNA-related activities. Existing computational methods utilize multiple lncRNA features or multiple protein features to predict lncRNA-protein interactions, but features are not available for all lncRNAs or proteins; most of existing methods are not capable of predicting interacting proteins (or lncRNAs) for new lncRNAs (or proteins), which don't have known interactions. In this paper, we propose the sequence-based feature projection ensemble learning method, "SFPEL-LPI", to predict lncRNA-protein interactions. First, SFPEL-LPI extracts lncRNA sequence-based features and protein sequence-based features. Second, SFPEL-LPI calculates multiple lncRNA-lncRNA similarities and protein-protein similarities by using lncRNA sequences, protein sequences and known lncRNA-protein interactions. Then, SFPEL-LPI combines multiple similarities and multiple features with a feature projection ensemble learning frame. In computational experiments, SFPEL-LPI accurately predicts lncRNA-protein associations and outperforms other state-of-the-art methods. More importantly, SFPEL-LPI can be applied to new lncRNAs (or proteins). The case studies demonstrate that our method can find out novel lncRNA-protein interactions, which are confirmed by literature. Finally, we construct a user-friendly web server, available at http://www.bioinfotech.cn/SFPEL-LPI/.

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SFPEL-LPI: Sequence-based feature projection ensemble learning for predicting LncRNA-protein interactions

Feature-derived graph regularized matrix factorization for predicting drug side effects

Bacterial small non-coding RNAs (sRNAs) have emerged as important elements in diverse physiological processes, including growth, development, cell proliferation, differentiation, metabolic reactions and carbon metabolism, and attract great attention. Accurate prediction of sRNAs is important and challenging, and helps to explore functions and mechanism of sRNAs. In this paper, we utilize a variety of sRNA sequence-derived features to develop ensemble learning methods for the sRNA prediction. First, we compile a balanced dataset and four imbalanced datasets. Then, we investigate various sRNA sequence-derived features, such as spectrum profile, mismatch profile, reverse compliment k-mer and pseudo nucleotide composition. Finally, we consider two ensemble learning strategies to integrate all features for building ensemble learning models for the sRNA prediction. One is the weighted average ensemble method (WAEM), which uses the linear weighted sum of outputs from the individual feature-based predictors to predict sRNAs. The other is the neural network ensemble method (NNEM), which trains a deep neural network by combining diverse features. In the computational experiments, we evaluate our methods on these five datasets by using 5-fold cross validation. WAEM and NNEM can produce better results than existing state-of-the-art sRNA prediction methods. WAEM and NNEM have great potential for the sRNA prediction, and are helpful for understanding the biological mechanism of bacteria.

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Sequence-based bacterial small RNAs prediction using ensemble learning strategies.

Bacterial small non-coding RNAs (sRNAs) play important roles in various physiological processes, and predicting sRNAs is an important task. In this paper, we develop a computational method for the sRNA prediction by using sRNA sequence-derived features. We investigate a variety of sRNA sequence-derived features, and evaluate the usefulness of features for the sRNA prediction. Then, we develop the sequence learning ensemble method, which uses the linear weighted sum of outputs from the individual feature-based predictors to predict sRNAs, and the genetic algorithm is adopted to optimize the parameters in the ensemble system. In the computational experiments, we compile a balanced dataset and four imbalanced datasets, and evaluate our method on these datasets by using 5-fold cross validation. The sequence learning ensemble method can achieve AUC scores greater than 0.9, and outperforms existing state-of-the-art sRNA prediction methods. In conclusion, the proposed method has a great potential for sRNA prediction. The source codes, datasets and supplementary are available in http://www.bioinfotech.cn/BIBM2017/SLEM.

Wenjian Wu

Papers

Predicting drug-disease associations by using similarity constrained matrix factorization

SFPEL-LPI: Sequence-based feature projection ensemble learning for predicting LncRNA-protein interactions

Feature-derived graph regularized matrix factorization for predicting drug side effects

Sequence-based bacterial small RNAs prediction using ensemble learning strategies.

Predicting small RNAs in bacteria via sequence learning ensemble method