The locations of the initiation of genomic DNA replication are defined as origins of replication sites (ORIs), which regulate the onset of DNA replication and play significant roles in the DNA replication process. The study of ORIs is essential for understanding the cell-division cycle and gene expression regulation. Accurate identification of ORIs will provide important clues for DNA replication research and drug development by developing computational methods. In this paper, the first integrated predictor named iORI-Euk was built to identify ORIs in multiple eukaryotes and multiple cell types. In the predictor, seven eukaryotic (Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana, Pichia pastoris, Schizosaccharomyces pombe and Kluyveromyces lactis) ORI data was collected from public database to construct benchmark datasets. Subsequently, three feature extraction strategies which are k-mer, binary encoding and combination of k-mer and binary were used to formulate DNA sequence samples. We also compared the different classification algorithms' performance. As a result, the best results were obtained by using support vector machine in 5-fold cross-validation test and independent dataset test. Based on the optimal model, an online web server called iORI-Euk (http://lin-group.cn/server/iORI-Euk/) was established for the novel ORI identification.

The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to a dramatic loss of human life worldwide. Despite many efforts, the development of effective drugs and vaccines for this novel virus will take considerable time. Artificial intelligence (AI) and machine learning (ML) offer promising solutions that could accelerate the discovery and optimization of new antivirals. Motivated by this, in this paper, we present an extensive survey on the application of AI and ML for combating COVID-19 based on the rapidly emerging literature. Particularly, we point out the challenges and future directions associated with state-of-the-art solutions to effectively control the COVID-19 pandemic. We hope that this review provides researchers with new insights into the ways AI and ML fight and have fought the COVID-19 outbreak.

Messenger RNAs (mRNAs) shoulder special responsibilities that transmit genetic code from DNA to discrete locations in the cytoplasm. The locating process of mRNA might provide spatial and temporal regulation of mRNA and protein functions. The situ hybridization and quantitative transcriptomics analysis could provide detail information about mRNA subcellular localization; however, they are time consuming and expensive. It is highly desired to develop computational tools for timely and effectively predicting mRNA subcellular location. In this work, by using binomial distribution and one-way analysis of variance, the optimal nonamer composition was obtained to represent mRNA sequences. Subsequently, a predictor based on support vector machine was developed to identify the mRNA subcellular localization. In 5-fold cross-validation, results showed that the accuracy is 90.12% for Homo sapiens (H. sapiens). The predictor may provide a reference for the study of mRNA localization mechanisms and mRNA translocation strategies. An online web server was established based on our models, which is available at http://lin-group.cn/server/iLoc-mRNA/.

Meiotic recombination is one of the most important driving forces of biological evolution, which is initiated by double-strand DNA breaks. Recombination has important roles in genome diversity and evolution. This review firstly provides a comprehensive survey of the 15 computational methods developed for identifying recombination hotspots in Saccharomyces cerevisiae. These computational methods were discussed and compared in terms of underlying algorithms, extracted features, predictive capability and practical utility. Subsequently, a more objective benchmark data set was constructed to develop a new predictor iRSpot-Pse6NC2.0 (http://lin-group.cn/server/iRSpot-Pse6NC2.0). To further demonstrate the generalization ability of these methods, we compared iRSpot-Pse6NC2.0 with existing methods on the chromosome XVI of S. cerevisiae. The results of the independent data set test demonstrated that the new predictor is superior to existing tools in the identification of recombination hotspots. The iRSpot-Pse6NC2.0 will become an important tool for identifying recombination hotspot.

MOTIVATION: DNA replication is a key step to maintain the continuity of genetic information between parental generation and offspring. The initiation site of DNA replication, also called origin of replication (ORI), plays an extremely important role in the basic biochemical process. Thus, rapidly and effectively identifying the location of ORI in genome will provide key clues for genome analysis. Although biochemical experiments could provide detailed information for ORI, it requires high experimental cost and long experimental period. As good complements to experimental techniques, computational methods could overcome these disadvantages. RESULTS: Thus, in this study, we developed a predictor called iORI-PseKNC2.0 to identify ORIs in the Saccharomyces cerevisiae genome based on sequence information. The PseKNC including 90 physicochemical properties was proposed to formulate ORI and non-ORI samples. In order to improve the accuracy, a two-step feature selection was proposed to exclude redundant and noise information. As a result, the overall success rate of 88.53% was achieved in the 5-fold cross-validation test by using support vector machine. AVAILABILITY AND IMPLEMENTATION: Based on the proposed model, a user-friendly webserver was established and can be freely accessed at http://lin-group.cn/server/iORI-PseKNC2.0. The webserver will provide more convenience to most of wet-experimental scholars.

MOTIVATION: DNA N4-methylcytosine (4mC) is an epigenetic modification. The knowledge about the distribution of 4mC is helpful for understanding its biological functions. Although experimental methods have been proposed to detect 4mC sites, they are expensive for performing genome-wide detections. Thus, it is necessary to develop computational methods for predicting 4mC sites. RESULTS: In this work, we developed iDNA4mC, the first webserver to identify 4mC sites, in which DNA sequences are encoded with both nucleotide chemical properties and nucleotide frequency. The predictive results of the rigorous jackknife test and cross species test demonstrated that the performance of iDNA4mC is quite promising and holds high potential to become a useful tool for identifying 4mC sites. AVAILABILITY AND IMPLEMENTATION: The user-friendly web-server, iDNA4mC, is freely accessible at http://lin.uestc.edu.cn/server/iDNA4mC. CONTACT: [email protected] or [email protected].

MOTIVATION: Nucleosome positioning participates in many cellular activities and plays significant roles in regulating cellular processes. With the avalanche of genome sequences generated in the post-genomic age, it is highly desired to develop automated methods for rapidly and effectively identifying nucleosome positioning. Although some computational methods were proposed, most of them were species specific and neglected the intrinsic local structural properties that might play important roles in determining the nucleosome positioning on a DNA sequence. RESULTS: Here a predictor called 'iNuc-PseKNC' was developed for predicting nucleosome positioning in Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster genomes, respectively. In the new predictor, the samples of DNA sequences were formulated by a novel feature-vector called 'pseudo k-tuple nucleotide composition', into which six DNA local structural properties were incorporated. It was observed by the rigorous cross-validation tests on the three stringent benchmark datasets that the overall success rates achieved by iNuc-PseKNC in predicting the nucleosome positioning of the aforementioned three genomes were 86.27%, 86.90% and 79.97%, respectively. Meanwhile, the results obtained by iNuc-PseKNC on various benchmark datasets used by the previous investigators for different genomes also indicated that the current predictor remarkably outperformed its counterparts. AVAILABILITY: A user-friendly web-server, iNuc-PseKNC is freely accessible at http://lin.uestc.edu.cn/server/iNuc-PseKNC.