Plasmids are extrachromosomal DNA molecules in bacteria and archaea, playing critical roles in horizontal gene transfer, antibiotic resistance, and pathogenicity. Since its first release in 2018, our database on plasmids, PLSDB, has significantly grown and enhanced its content and scope. From 34 513 records contained in the 2021 version, PLSDB now hosts 72 360 entries. Designed to provide life scientists

CATH (https://www.cathdb.info) is a structural classification database that assigns domains to the structures in the Protein Data Bank (PDB) and AlphaFold Protein Structure Database (AFDB) and adds layers of biological information, including homology and functional annotation. This article covers developments in the CATH classification since 2021. We report the significant expansion of structural information

Prions represent epigenetic regulator proteins that can self-propagate their structure and confer their misfolded structure and function on normally folded proteins. Like the mammalian prion PrPSc, prions also occur in fungi. While a few prions, like Swi1, affect gene expression, none are shown to affect heterochromatin structure and function. In fission yeast and metazoans, histone methyltransferase

By processing and abstracting diverse omics datasets into associations between genes and their attributes, the Harmonizome database enables researchers to explore and integrate knowledge about human genes from many central omics resources. Here, we introduce Harmonizome 3.0, a significant upgrade to the original Harmonizome database. The upgrade adds 26 datasets that contribute nearly 12 million associations

LINE-1 (L1) is a parasitic retrotransposable DNA element, active in primates for the last 80–120 Myr. L1 has generated nearly one-third of the human genome by copying its transcripts, and those of other genetic elements (e.g. Alu and SVA), into genomic DNA by target site-primed reverse transcription (TPRT) and remains active in modern humans. L1 encodes two proteins that bind their encoding transcript

Elevations in intracellular glucose concentrations are essential for epithelial cell differentiation by mechanisms that are not fully understood. Glucose has recently been found to directly bind several proteins to alter their functions to enhance differentiation. Among the newly identified glucose-binding proteins is NSUN2, an RNA-binding protein that we identified as indispensable for epidermal differentiation

The Proteome-Wide Association Study (PWAS) is a protein-based genetic association approach designed to complement traditional variant-based methods like GWAS. PWAS operates in two stages: first, machine learning models predict the impact of genetic variants on protein-coding genes, generating effect scores. These scores are then aggregated into a gene-damaging score for each individual. This score

InterPro (https://www.ebi.ac.uk/interpro) is a freely accessible resource for the classification of protein sequences into families. It integrates predictive models, known as signatures, from multiple member databases to classify sequences into families and predict the presence of domains and significant sites. The InterPro database provides annotations for over 200 million sequences, ensuring extensive

The p53 family of transcription factors (p53, p63 and p73) regulate diverse organismal processes including tumor suppression, maintenance of genome integrity and the development of skin and limbs. Crosstalk between transcription factors with highly similar DNA binding profiles, like those in the p53 family, can dramatically alter gene regulation. While p53 is primarily associated with transcriptional

The evolutionary classification of protein domains (ECOD) classifies protein domains using a combination of sequence and structural data (http://prodata.swmed.edu/ecod). Here we present the culmination of our previous efforts at classifying domains from predicted structures, principally from the AlphaFold Database (AFDB), by integrating these domains with our existing classification of PDB structures

Pharmacogenomics, the study of how an individual's genetic makeup influences their response to medications, is a rapidly evolving field with significant implications for personalized medicine. As researchers and healthcare professionals face challenges in exploring the intricate relationships between genetic profiles and therapeutic outcomes, the demand for effective and user-friendly tools to access

Transcriptional rewiring generates phenotypic novelty, acting as an important mechanism contributing to evolutionary development, speciation, and adaptation in all organisms. The phenotypic outcomes (functions) of transcription factor (TF) activity are determined by the combined effects of all target genes in the TF’s regulatory network. Plastic rewiring of target genes accumulates during species divergence

Genomic, epigenomic and transcriptomic alterations are hallmarks of cancer cells, and are closely connected. Especially, epigenetic regulation plays a critical role in tumorigenesis and progression. The growing single-cell epigenome data in cancer research provide new opportunities for data mining from a more comprehensive perspective. However, there is still a lack of databases designed for interactively

The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena), maintained at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) provides freely accessible services, both for deposition of, and access to, open nucleotide sequencing data. Open scientific data are of paramount importance to the scientific community and contribute daily to the acceleration of scientific

GenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public data repository that contains 34 trillion base pairs from over 4.7 billion nucleotide sequences for 581 000 formally described species. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. We summarize the content of the database in 2025 and recent updates such

Organismal aging is marked by decline in cellular function and anatomy, ultimately resulting in death. To inform our understanding of the mechanisms underlying this degeneration, we performed standard RNA sequencing (RNA-seq) and Oxford Nanopore Technologies direct RNA-seq over an adult time course in Caenorhabditis elegans. Long reads allowed for identification of hundreds of novel isoforms and age-associated

Deep mutational scanning is a powerful method for exploring the mutational fitness landscape of proteins. Its adaptation to anti-CRISPR proteins, which are natural CRISPR-Cas inhibitors and key players in the co-evolution of microbes and phages, facilitates their characterization and optimization. Here, we developed a robust anti-CRISPR deep mutational scanning pipeline in Escherichia coli that combines

PubChem (https://pubchem.ncbi.nlm.nih.gov) is a large and highly-integrated public chemical database resource at NIH. In the past two years, significant updates were made to PubChem. With additions from over 130 new sources, PubChem contains >1000 data sources, 119 million compounds, 322 million substances and 295 million bioactivities. New interfaces, such as the consolidated literature panel and

RNA-binding proteins are essential for gene regulation and the spatial organization of cells. Here, we report that the yeast ribosome biogenesis factor Loc1p is an intrinsically disordered RNA-binding protein with eight repeating positively charged, unstructured nucleic acid binding (PUN) motifs. While a single of these previously undefined motifs stabilizes folded RNAs, multiple copies strongly cooperate

Many RNAs associate with chromatin, either directly or indirectly. Several technologies for mapping regions where RNAs interact across the genome have been developed to investigate the function of these RNAs. Obtaining information on the proteins involved in these RNA–chromatin interactions is critical for further analysis. Here, we developed RADIP [RNA and DNA interacting complexes ligated and sequenced

The Plant Metabolic Network (PMN) is a free online database of plant metabolism available at https://plantcyc.org. The latest release, PMN 16, provides metabolic databases representing >1200 metabolic pathways, 1.3 million enzymes, >8000 metabolites, >10 000 reactions and >15 000 citations for 155 plant and green algal genomes, as well as a pan-plant reference database called PlantCyc. This release

Rice (Oryza sativa L.) is a major cereal crop that provides calories across the world. With a small genome, rice has been used extensively as a model for genetic and genomic studies in the Poaceae. Since the release of the first rice genome sequence in 2002, an improved reference genome assembly, multiple whole genome assemblies, extensive gene expression profiles, and resequencing data from over 3000

Proteins cooperate, regulate and bind each other to achieve their functions. Understanding the complex network of their interactions is essential for a systems-level description of cellular processes. The STRING database compiles, scores and integrates protein–protein association information drawn from experimental assays, computational predictions and prior knowledge. Its goal is to create comprehensive

Unraveling the causal variants from genome wide association studies (GWASs) is pivotal for understanding genetic underpinnings of complex traits and diseases. Despite continuous efforts, tools to refine and prioritize GWAS signals need enhancement to address the direct causal implications of genetic variations. To overcome challenges related to statistical fine-mapping in identifying causal variants

Response to spatiotemporal variation in selection gradients resulted in signatures of polygenic adaptation in human genomes. We introduce RAISING, a two-stage deep learning framework that optimizes neural network architecture through hyperparameter tuning before performing feature selection and prediction tasks. We tested RAISING on published and newly designed simulations that incorporate the complex

Alternative splicing (AS) is a crucial mechanism to regulate gene expression and protein complexity. RNA-binding proteins (RBPs) play an important role in regulating abnormal alternative splicing in cancers. However, few resources are available to identify specific RBPs responsible for regulating individual AS event. We have developed the OncoSplicing database for integrative analysis of clinically

Space biology and health data are critical for the success of deep space missions and sustainable human presence off-world. At the core of effectively managing biomedical risks is the commitment to open science principles, which ensure that data are findable, accessible, interoperable, reusable, reproducible and maximally open. The 2021 integration of the Ames Life Sciences Data Archive with GeneLab

Clinical trials and meta-analyses are considered high-level medical evidence with solid credibility. However, such clinical evidence for traditional Chinese medicine (TCM) is scattered, requiring a unified entrance to navigate all available evaluations on TCM therapies under modern standards. Besides, novel experimental evidence has continuously accumulated for TCM since the publication of HERB 1.0

The Chemical Probes Portal (www.chemicalprobes.org) is a free, public resource, based on expert-reviews, that supports the assessment, selection and use of small-molecule compounds that qualify as chemical probes. These high-quality reagents are essential for exploring the function of individual proteins in complex biological systems, such as cells and organisms, and for validating proteins as potential

Mutations that introduce premature termination codons (PTCs) within protein-coding genes are associated with incurable and severe genetic diseases. Many PTC-associated disorders are life-threatening and have no approved medical treatment options. Suppressor transfer RNAs (sup-tRNAs) with the capacity to translate PTCs represent a promising therapeutic strategy to treat these conditions; however, developing

The yeast Sae2 protein, known as CtIP in mammals, once phosphorylated at Ser267, stimulates the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex to cleave DNA ends that possess hairpin structures or protein blocks, such as the Spo11 transesterase or trapped topoisomerases. Stimulation of the Mre11 endonuclease by Sae2 depends on a Rad50–Sae2 interaction, but the mechanism by which this is

G protein-coupled receptors (GPCRs) are membrane-spanning transducers mediating the actions of numerous physiological ligands and drugs. The GPCR database GPCRdb supports a large global research community with reference data, analysis, visualization, experiment design and dissemination. Here, we describe our sixth major GPCRdb release starting with an overview of all resources for receptors and ligands

MatrixDB, a member of the International Molecular Exchange consortium (IMEx), is a curated interaction database focused on interactions established by extracellular matrix (ECM) constituents including proteins, proteoglycans, glycosaminoglycans and ECM bioactive fragments. The architecture of MatrixDB was upgraded to ease interaction data export, allow versioning and programmatic access and ensure

Suppression of single-stranded DNA (ssDNA) gap accumulation at replication forks has emerged as a potential determinant of chemosensitivity in homologous recombination (HR)-deficient tumors, as ssDNA gaps are transformed into cytotoxic double-stranded DNA breaks. We have previously shown that the histone chaperone CAF-1’s nucleosome deposition function is vital to preventing degradation of stalled

The Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated reference database for molecular complexes. It is a unifying web resource linking aggregated data on composition, topology and the function of macromolecular complexes from 28 species. In addition to significantly extending the number of manually curated complexes, we have massively extended the coverage of the human complexome

RNA Guanine-quadruplexes (rG4s) are important nucleic acid structures that govern vital biological processes. Although numerous tools have been developed to target rG4s, few specific tools are capable of discerning individual rG4 of interest. Herein, we design and synthesize the first L-aptamer–antisense oligonucleotide (ASO) conjugate, L-Apt.4–1c-ASO15nt(APP), with a focus on recognizing the amyloid

Non-canonical DNA structures, such as the G-quadruplex (G4) and i-motif (iM), are formed at guanine- and cytosine-rich sequences, respectively, in living cells and involved in regulating various biological processes during the cell cycle. Therefore, the formation and resolution of these non-canonical structures must be dynamically regulated by physiological conditions or factors that can bind G4 and

Clustered regularly-interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins protect bacteria and archaea from their viruses, and anti-CRISPRs (Acrs) are small virus-encoded proteins that inhibit CRISPR-Cas immunity. Over 80 families of Acrs have been described to date; however, only three of these subvert Type III CRISPR-Cas immunity. Type III systems employ a complex network

Spatial transcriptomics sequencing technology deepens our understanding of the diversity of cell behaviors, fates and states within complex tissue, which is often determined by the fine-tuning of regulatory network functional activities. Therefore, characterizing the functional activity within tissue space is helpful for revealing the functional features that drive spatial heterogeneity, and understanding

RNA molecules function in numerous biological processes by folding into intricate structures. Here we present RASP v2.0, an updated database for RNA structure probing data featuring a substantially expanded collection of datasets along with enhanced online structural analysis functionalities. Compared to the previous version, RASP v2.0 includes the following improvements: (i) the number of RNA structure

Secondary metabolites are small molecules produced by all corners of life, often with specialized bioactive functions with clinical and environmental relevance. Secondary metabolite biosynthetic gene clusters (BGCs) can often be identified within DNA sequences by various sequence similarity tools, but determining the exact functions of genes in the pathway and predicting their chemical products can

Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency

SETDB1 (SET domain bifurcated histone lysine methyltransferase 1) is a major protein lysine methyltransferase trimethylating lysine 9 on histone H3 (H3K9) which is involved in heterochromatin formation and silencing of repeat elements (REs). It contains a unique Triple Tudor Domain (3TD), which specifically binds the dual modification of H3K14ac in the presence of H3K9me1/2/3. Here, we explored the

Gene therapy, which involves the delivery of genetic material into cells to correct an underlying genetic problem, has emerged as a promising approach for treating various conditions. To promote research in this rapidly evolving field, we developed the Gene Therapy Omnibus (GTO) (http://www.inbirg.com/gto/), a comprehensive resource containing detailed clinical trial data and molecular information

Antimicrobial resistance is one of the most urgent global health threats, especially in the post-pandemic era. Antimicrobial peptides (AMPs) offer a promising alternative to traditional antibiotics, driving growing interest in recent years. dbAMP is a comprehensive database offering extensive annotations on AMPs, including sequence information, functional activity data, physicochemical properties and

MiRNAs represent a non-coding RNA class that regulate gene expression and pathways. While miRNAs are evolutionary conserved most data stems from Homo sapiens and Mus musculus. As miRNA expression is highly tissue specific, we developed miRNATissueAtlas to comprehensively explore this landscape in H. sapiens. We expanded the H. sapiens tissue repertoire and included M. musculus. In past years, the number

The Pfam protein families database is a comprehensive collection of protein domains and families used for genome annotation and protein structure and function analysis (https://www.ebi.ac.uk/interpro/). This update describes major developments in Pfam since 2020, including decommissioning the Pfam website and integration with InterPro, harmonization with the ECOD structural classification, and expanded

Ribosome profiling (Ribo-Seq) has revolutionised our understanding of translation, but the increasing complexity and volume of Ribo-Seq data present challenges for its reuse. Here, we formally introduce RiboSeq.Org, an integrated suite of resources designed to facilitate Ribo-Seq data analysis and visualisation within a web browser. RiboSeq.Org comprises several interconnected tools: GWIPS-viz for

The members of the International Nucleotide Sequence Database Collaboration (INSDC; https://insdc.org) have built systems to collect, archive and disseminate sequence data for more than four decades. The three collaborating organizations, the National Library of Medicine, National Center for Biotechnology Information (NLM-NCBI) in the United States, Research Organization of Information and Systems

Single-cell RNA sequencing (scRNA-seq) has emerged as the key technique for studying transcriptomics at the single-cell level. In our previous work, we presented the DISCO database (https://www.immunesinglecell.org/) that integrates publicly available human scRNA-seq data. We now introduce an enhanced version of DISCO, which has expanded fourfold to include >100 million cells from >17 thousand samples

Molecular Dynamics (MD) simulation of biomolecules provides important insights into conformational changes and dynamic behavior, revealing critical information about folding and interactions with other molecules. The collection of simulations stored in computers across the world holds immense potential to serve as training data for future Machine Learning models that will transform the prediction of

canSAR (https://cansar.ai) continues to serve as the largest publicly available platform for cancer-focused drug discovery and translational research. It integrates multidisciplinary data from disparate and otherwise siloed public data sources as well as data curated uniquely for canSAR. In addition, canSAR deploys a suite of curation and standardization tools together with AI algorithms to generate

The NIH policy on sex as biological variable (SABV) emphasized the importance of sex-based differences in precision oncology. Over 50% of clinically actionable oncology genes are sex-biased, indicating differences in drug efficacy. Research has identified sex differences in non-reproductive cancers, highlighting the need for comprehensive sex-based cancer data. We therefore developed OncoSexome, a

BitterDB (http://bitterdb.agri.huji.ac.il) was introduced in 2012 as a central resource for information on bitter-tasting molecules and their receptors, and was updated in 2019. The information in BitterDB is used for tasks such as exploring the bitter chemical space, choosing suitable ligands for experimental studies, analyzing receptors’ selectivity and promiscuity, and developing machine learning

MarkerDB (https://markerdb.ca) has become a leading resource for comprehensive information on molecular biomarkers. Over the past 3 years, the database has evolved significantly, reflecting the dynamic landscape of biomarker research and increasing demands from its user community. This year’s update, which is called MarkerDB 2.0, introduces key improvements to enhance the database’s usability, consistency

OrthoDB (https://www.orthodb.org) offers evolutionary and functional annotations of orthologous genes in the widest sampling of eukaryotes, prokaryotes, and viruses, extending experimental gene function knowledge to newly sequenced genomes. We collect gene annotations, delineate hierarchical gene orthology and annotate the orthologous groups (OGs) with functional and evolutionary traits. OrthoDB is

Conformational changes in a transcription factor can significantly affect its transcriptional activity. The activated form of the FOXM1 transcription factor regulates the transcriptional network of genes essential for cell cycle progression and carcinogenesis. However, the mechanism and impact of FOXM1 conformational change on its transcriptional activity in vivo throughout the cell cycle progression