Abstract MicroRNAs (miRNAs) are key post-transcriptional regulators in gene regulatory networks (GRNs). Comprehensive research on miRNAs increasingly requires the integration of large and heterogeneous datasets, together with more efficient approaches to knowledge exploration. Here, we present PmiREN3.0, a major update of the Plant MicroRNA Encyclopedia. Compared with PmiREN2.0, species/subspecies coverage increased from 179 to 340, adding 22 orders, 51 families, and 108 genera. Using the same standardized workflow and annotation criteria as previous releases, high-confidence miRNAs were identified from 5319 small RNA sequencing (sRNA-seq) datasets, with miRNA loci increasing from 39 751 to 87 667 and miRNA families from 7838 to 18 389. Resources and tools from previous releases were extensively updated, while six new modules were added for primary transcripts, DNA methylation, RNA modifications, stress-responsive expression, metabolic pathways, and core GRNs. PmiREN3.0 also introduces miRai+, a knowledge service powered by artificial intelligence (AI) that combines a language model fine-tuned on miRNA knowledge with retrieval augmented generation. Evaluation yielded scores of 0.910 for answer relevance, 0.965 for faithfulness, and 0.906 for factual correctness. Together, PmiREN3.0 provides an expanded plant miRNA dataset and an integrated platform combining multi-omics data and AI-assisted knowledge services for plant miRNA research. PmiREN3.0 is available at https://pmiren.com/.
Abstract The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena), hosted at EMBL’s European Bioinformatics Institute, is an open resource that supports the global life sciences community by enabling submission, archiving, dissemination, and reuse of the world’s nucleotide sequencing data. In 2026, the ENA continues to explore and address challenges related to a rapidly evolving landscape. This includes sustaining the growth of the data volume, increasing diversity in data types, the need for more standardized metadata, and the connection of sequence data with data from other disciplines. To address these challenges, the ENA has enhanced its services to adopt the INSDC minimum specification for data requirements, introduce new sample checklists and collaborate on an experiment checklist, and progress on the implementation of GFF3 for annotations. The ENA continues to support global science through its global engagement that includes understanding its Access and Benefit Sharing (ABS) requirements to the wider community. Sustainability is a major aspect of the archive, which has seen updates to incremental indexing and SRA read removal. Additionally, the broker community continues to be supported and expanded. In this paper, we discuss these challenges and opportunities as we continue to keep pace with the evolving life science data resource ecosystem and requirements.
Abstract Quantitative binding affinities and three-dimensional protein–ligand structures provide complementary information essential for structure-based drug discovery, yet these data remain largely disconnected across existing databases and the biomedical literature. We present BioLiP3, a major extension of BioLiP that expands quantitative affinity coverage 13-fold within its structure-centered framework for biologically relevant interactions. BioLiP3 contains 593 423 affinity records, of which 591 820 are linked to three-dimensional protein–ligand structures: 45 386 experimentally resolved PDB complexes, 528 732 BindingDB-derived records with computationally generated structures, and 17 702 structure-linked records derived from LLM-mined biomedical literature. For records lacking experimental complex structures, we generate structural models using available experimental or predicted receptor structures, binding-site identification, and molecular docking, with experimental and computational structures explicitly distinguished. To complement existing databases, we developed a hybrid literature-mining workflow combining large language models with rule-based validation and independent verification to extract Ki, Kd, IC50, and EC50 measurements from PubMed abstracts while preserving provenance. BioLiP3 further integrates ligand-binding sites and protein, functional, and structural annotations via cross-references to PDB, UniProt, NCBI Taxonomy, PubChem, and original literature. Taken together, these advances make BioLiP3 a unified resource for data-driven protein–ligand interaction studies and structure-based drug design. BioLiP3 is freely accessible at https://zhanggroup.org/BioLiP/.
Abstract The gut plays key roles in digestion, nutrient absorption, and immunity. A variety of gut-related diseases have shown great heterogeneity in many aspects, including molecular characteristics, cellular composition, and microbial communities, which may reveal disease-specific therapeutic targets. In recent years, large-scale datasets have emerged to decipher associations between gut-related diseases and characteristics. However, these valuable data are independently scattered in different studies, and no comprehensive resource is available for integrating these data, which limits systematic investigation and cross-disease comparisons. To address this, we developed gutDBase (https://bio-computing.hrbmu.edu.cn/gutDBase), a comprehensive database that systematically integrates transcriptomic and microbial data for 15 gut-related diseases, curated from 175 bulk and single-cell datasets derived from 161 publications. gutDBase provides a user-friendly, interactive interface, and rich visualization tools to display the expression patterns and microbial compositions of different diseases from multiple perspectives. This resource is intended to support studies of disease mechanisms, facilitate target discovery, and advance translational research in gut-related diseases.
Abstract Replication origins are essential for both chromosome duplication and plasmid maintenance; however, their annotation remains challenging across different replicon types and across diverse phylogenetic lineages. DoriC 14.0, the latest update of the database of replication origins in prokaryotic genomes, restructures and greatly expands this resource, with particular emphasis on plasmid replication. The latest release contains 530 178 computationally derived origin records, associated with 432 232 distinct sequence accessions, including 434 060 chromosomal and 96 118 plasmid records from bacteria and archaea. For bacterial plasmids, OriV-Finder was applied with RNA II-based refinement, whereas a customized OriV-Finder pipeline was employed for archaeal plasmids, which relies on archaeal replication-associated proteins and origin recognition box motifs. DoriC 14.0 combines literature evidence with computational predictions, maintains traceable record identifiers, and offers versioned data with release history. New features include comparative sequence support, related-origin links, interactive candidate replication initiation protein (RIP) sequence-similarity networks, plasmid-level analyses of origin recurrence, RIP profiles, and RNA II variation. The updated website provides filter-based browsing, record-level views, BLAST searches, and standardized downloads, and is freely accessible at https://tubic.org/doric/ and https://tubic.tju.edu.cn/doric/ without registration.
