MIB2 (metal ion-binding) attempts to overcome the limitation of structure-based prediction approaches, with many proteins lacking a solved structure. MIB2 also offers more accurate prediction performance and more metal ion types. MIB2 utilizes both the (PS)² method and the AlphaFold Protein Structure Database to acquire predicted structures to perform metal ion docking and predict binding residues. MIB2 offers marked improvements over MIB by collecting more MIB residue templates and using the metal ion type-specific scoring function. It offers a total of 18 types of metal ions for binding site predictions. Freely available on the web at http://bioinfo.cmu.edu.tw/MIB2/. Supplementary data are available at Bioinformatics online.

Human pathologies such as Alzheimer’s disease, type 2 diabetes-induced insulin resistance, cancer, and cardiovascular diseases have altered lipid homeostasis. Among these imbalanced lipids, the bioactive sphingolipids ceramide and sphingosine-1 phosphate (S1P) are pivotal in the pathophysiology of these diseases. Several enzymes within the sphingolipid pathway contribute to the homeostasis of ceramide and S1P. Ceramidase is key in the degradation of ceramide into sphingosine and free fatty acids. In humans, five different ceramidases are known—acid ceramidase, neutral ceramidase, and alkaline ceramidase 1, 2, and 3—which are encoded by five different genes (ASAH1, ASAH2, ACER1, ACER2, and ACER3, respectively). Notably, the neutral ceramidase N-acylsphingosine amidohydrolase 2 (ASAH2) shows considerable differences between humans and animals in terms of tissue expression levels. Besides, the subcellular localization of ASAH2 remains controversial. In this review, we sum up the results obtained for identifying gene divergence, structure, subcellular localization, and manipulating factors and address the role of ASAH2 along with other ceramidases in human diseases.

With the advance of next generation sequencing techniques, whole genome sequencing (WGS) is expected to become the optimal method for molecular subtyping of bacterial isolates. To use WGS as a general subtyping method for disease outbreak investigation and surveillance, the layout of WGS-based typing must be comparable among laboratories. Whole genome multilocus sequence typing (wgMLST) is an approach that achieves this requirement. To apply wgMLST as a standard subtyping approach, a pan-genome allele database (PGAdb) for the population of a bacterial organism must first be established. We present a free web service tool, PGAdb-builder (http://wgmlstdb.imst.nsysu.edu.tw), for the construction of bacterial PGAdb. The effectiveness of PGAdb-builder was tested by constructing a pan-genome allele database for Salmonella enterica serovar Typhimurium, with the database being applied to create a wgMLST tree for a panel of epidemiologically well-characterized S. Typhimurium isolates. The performance of the wgMLST-based approach was as high as that of the SNP-based approach in Leekitcharoenphon’s study used for discerning among epidemiologically related and non-related isolates.

ProbioMinServer is a platform designed to help researchers access information on probiotics regarding a wide variety of characteristics, such as safety (e.g., antimicrobial resistance, virulence, pathogenic, plasmid and prophage genes) and functionality (e.g., functional classes, carbohydrate-active enzyme, and metabolite gene cluster profile). Because probiotics are functional foods, their safety and functionality are a crucial part of health care. Genomics has become a crucial methodology for investigating the safety and functionality of probiotics in food and feed. This shift is primarily attributed to the growing affordability of next-generation sequencing technologies. However, no integrated platform is available for simultaneously evaluating probiotic strain safety, investigating probiotic functionality, and identifying known phylogenetically related strains. Thus, we constructed a new platform, ProbioMinServer, which incorporates these functions. ProbioMinServer accepts whole-genome sequence files in the FASTA format. If the query genome belongs to the 25 common probiotic species collected in our database, the server performs a database search and analyzes the core-genome multilocus sequence typing (cgMLST). Front-end applications were implemented in JavaScript with a bootstrap framework, and back-end programs were implemented using PHP, Perl, and Python. ProbioMinServer can help researchers quickly and easily retrieve information on the safety and functionality of various probiotics. The platform is available at https://probiomindb.imst.nsysu.edu.tw. Supplementary data are available at Bioinformatics Advances online.

With the decreasing cost of next-generation sequencing, whole-genome sequence-based bacterial genome comparisons are expected to become a mainstream process in the public health domain. Extended multilocus sequence typing (MLST) methods are becoming increasingly popular for use in comparing bacterial genetic relatedness in epidemiological investigations. Several extended MLST schemes based on biological signatures have been reported. Among them, whole-genome MLST (wgMLST) has gradually become one of the most widely used approaches for bacterial strain typing. In addition to using bacterial typing, many researchers aim to identify differences in the genes of compared strains. Because these differences might provide insights into critical bacterial functions, such as virulence and pathogenicity, researchers usually study these genes that differ between strains. Hence, we designed a web service tool based on wgMLST-constructed tree topology coupled with the feature selection method to create the “canonical wgMLST (cano-wgMLST) tree.” The genes that differ between strains are shown at each split of the tree, thereby directly providing information for performing a comparative genomic analysis for each strain pair. We demonstrated that this web service tool could be operated efficiently on two datasets consisting of 22 Campylobacter jejuni isolates and 59 S. Heidelberg isolates, respectively. We imposed this tool on a designated web server, cano-wgMLST_BacCompare, to enable users to create a wgMLST tree and canonical wgMLST tree automatically from their uploaded bacterial genomes for not only epidemiological investigation but also comparative genomic analysis. Additionally, detailed information on how to use this service is provided. The cano-wgMLST_BacCompare is available at http://baccompare.imst.nsysu.edu.tw.

Taxonomic relationships between Lactobacillus casei , Lactobacillus paracasei and Lactobacillus zeae have long been debated. Results of previous analyses have shown that overall genome relatedness indices (such as average nucleotide identity and core nucleotide identity) between the type strains L. casei ATCC 393^T and L. zeae ATCC 15820^T were 94.6 and 95.3 %, respectively, which are borderline for species definition. However, the digital DNA‒DNA hybridization value was 57.3 %, which was clearly lower than the species delineation threshold of 70 %, and hence raised the possibility that L. casei could be reclassified into two species. To re-evaluate the taxonomic relationship of these taxa, multilocus sequence analysis (MLSA) based on the concatenated five housekeeping gene (dnaJ, dnaK, mutL, pheS and yycH) sequences, phylogenomic and core genome multilocus sequence typing analyses, gene presence and absence profiles using pan-genome analysis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling analysis, cellular fatty acid compositions, and phenotype analysis were carried out. The results of phenotypic characterization, MLSA, whole-genome sequence-based analyses and MALDI-TOF MS profiling justified an independent species designation for the L. zeae strains, and supported an emended the description of the name of Lactobacillus zeae (ex Kuznetsov 1956) Dicks et al. 1996, with ATCC 15820^T (=DSM 20178^T=BCRC 17942^T) as the type strain.