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We construct a virus database called VirusDB (http://yaulab.math.tsinghua.edu.cn/VirusDB/) and an online inquiry system to serve people who are interested in viral classification and prediction. The database stores all viral genomes, their corresponding natural vectors, and the classification information of the single/multiple-segmented viral reference sequences downloaded from National Center for Biotechnology Information. The online inquiry system serves the purpose of computing natural vectors and their distances based on submitted genomes, providing an online interface for accessing and using the database for viral classification and prediction, and back-end processes for automatic and manual updating of database content to synchronize with GenBank. Submitted genomes data in FASTA format will be carried out and the prediction results with 5 closest neighbors and their classifications will be returned by email. Considering the one-to-one correspondence between sequence and natural vector, time efficiency, and high accuracy, natural vector is a significant advance compared with alignment methods, which makes VirusDB a useful database in further research.

Next-generation sequencing technology enables the routine detection of bacterial pathogens for clinical diagnostics and genetic research. Whole-genome sequencing has been of importance in the epidemiologic analysis of bacterial pathogens. However, few whole-genome sequencing-based genotyping pipelines are available for practical applications. Here, we present the whole-genome sequencing-based single nucleotide polymorphism(SNP) genotyping method and apply to the evolutionary analysis of methicillin-resistant Staphylococcus aureus. The SNP genotyping method calls genome variants using next-generation sequencing reads of whole genomes and calculates the pair-wise Jaccard distances of the genome variants. The method may reveal the high-resolution whole-genome SNP profiles and the structural variants of different isolates of methicillin-resistant S. aureus(MRSA) and methicillin-susceptible S. aureus(MSSA) strains. The phylogenetic analysis of whole genomes and particular regions may monitor and track the evolution and the transmission dynamic of bacterial pathogens. The computer pro- grams of the whole genome sequencing-based SNP genotyping methods are available to the public at https://github. com/ cyinbox/NGS.

In 1960s, Almgren initiated a program to find minimal hypersurfaces in compact manifolds using min-max method. This program was largely advanced by Pitts and Schoen-Simon in 1980s when the manifold has no boundary. In this paper, we finish this program for general compact manifold with nonempty boundary. As a result, we prove the existence of a smooth embedded minimal hypersurface with free boundary in any compact smooth Euclidean domain. An application of our general existence result combined with the work of Marques and Neves shows that for any compact Riemannian manifolds with nonnegative Ricci curvature and convex boundary, there exist infinitely many embedded minimal hypersurfaces with free boundary which are properly embedded.