AbstractThe 2021 Nucleic Acids Research database Issue contains 189 papers spanning a wide range of biological fields and investigation. It includes 89 papers reporting on new databases and 90 covering recent changes to resources previously published in the Issue. A further ten are updates on databases most recently published elsewhere. Seven new databases focus on COVID-19 and SARS-CoV-2 and many

The construction of microbial cell factories for sustainable production of chemicals and pharmaceuticals requires extensive genome engineering. Using Saccharomyces cerevisiae, this study proposes synthetic neochromosomes as orthogonal expression platforms for rewiring native cellular processes and implementing new functionalities. Capitalizing the powerful homologous recombination capability of S.

AbstractVIrus Particle ExploreR data base (VIPERdb) (http://viperdb.scripps.edu) is a curated repository of virus capsid structures and a database of structure-derived data along with various virus specific information. VIPERdb has been continuously improved for over 20 years and contains a number of virus structure analysis tools. The release of VIPERdb v3.0 contains new structure-based data analytics

AbstractProtein subcellular localization (SCL) is important for understanding protein function, genome annotation, and aids identification of potential cell surface diagnostic markers, drug targets, or vaccine components. PSORTdb comprises ePSORTdb, a manually curated database of experimentally verified protein SCLs, and cPSORTdb, a pre-computed database of PSORTb-predicted SCLs for NCBI’s RefSeq deduced

AbstractThe Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242

AbstractThe Human Microbiome Project (HMP) explored microbial communities of the human body in both healthy and disease states. Two phases of the HMP (HMP and iHMP) together generated >48TB of data (public and controlled access) from multiple, varied omics studies of both the microbiome and associated hosts. The Human Microbiome Project Data Coordination Center (HMPDACC) was established to provide

AbstractNumerous lines of evidence have shown that the interaction between the nuclear and mitochondrial genomes ensures the efficient functioning of the OXPHOS complexes, with substantial implications in bioenergetics, adaptation, and disease. Their interaction is a fascinating and complex trait of the eukaryotic cell that MitImpact explores with its third major release. MitImpact expands its collection

AbstractPANTHER (Protein Analysis Through Evolutionary Relationships, http://www.pantherdb.org) is a resource for the evolutionary and functional classification of protein-coding genes from all domains of life. The evolutionary classification is based on a library of over 15,000 phylogenetic trees, and the functional classifications include Gene Ontology terms and pathways. Here, we analyze the current

AbstractThe Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding the functions of genes and gene products. Here, we report the advances of the consortium over the past two years. The new GO-CAM annotation framework was notably improved, and we formalized the model with a computational schema to check and validate the rapidly

AbstractThe Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) contains nearly 200 000 bacterial and archaeal genomes and 150 million proteins with up-to-date annotation. Changes in the Prokaryotic Genome Annotation Pipeline (PGAP) since 2018 have resulted in a substantial reduction in spurious annotation. The hierarchical collection of protein family models

AbstractDNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes

AbstractG protein-coupled receptors (GPCRs) form both the largest family of membrane proteins and drug targets, mediating the action of one-third of medicines. The GPCR database, GPCRdb serves >4 000 researchers every month and offers reference data, analysis of own or literature data, experiment design and dissemination of published datasets. Here, we describe new and updated GPCRdb resources with

AbstractThe GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures

AbstractSoyBase, a USDA genetic and genomics database, holds professionally curated soybean genetic and genomic data, which is integrated and made accessible to researchers and breeders. The site holds several reference genome assemblies, as well as genetic maps, thousands of mapped traits, expression and epigenetic data, pedigree information, and extensive variant and genotyping data sets. SoyBase

AbstractPharmacotranscriptomics has become a powerful approach for evaluating the therapeutic efficacy of drugs and discovering new drug targets. Recently, studies of traditional Chinese medicine (TCM) have increasingly turned to high-throughput transcriptomic screens for molecular effects of herbs/ingredients. And numerous studies have examined gene targets for herbs/ingredients, and link herbs/ingredients

AbstractThe Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from

AbstractPAGER-CoV (http://discovery.informatics.uab.edu/PAGER-CoV/) is a new web-based database that can help biomedical researchers interpret coronavirus-related functional genomic study results in the context of curated knowledge of host viral infection, inflammatory response, organ damage, and tissue repair. The new database consists of 11 835 PAGs (Pathways, Annotated gene-lists, or Gene signatures)

AbstractDeregulation of microRNA (miRNA) expression plays a critical role in the transition from a physiological to a pathological state. The accurate miRNA promoter identification in multiple cell types is a fundamental endeavor towards understanding and characterizing the underlying mechanisms of both physiological as well as pathological conditions. DIANA-miRGen v4 (www.microrna.gr/mirgenv4) provides

AbstractMarkerDB is a freely available electronic database that attempts to consolidate information on all known clinical and a selected set of pre-clinical molecular biomarkers into a single resource. The database includes four major types of molecular biomarkers (chemical, protein, DNA [genetic] and karyotypic) and four biomarker categories (diagnostic, predictive, prognostic and exposure). MarkerDB

AbstractThe European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk/) provides freely available data and bioinformatics services to the scientific community, alongside its research activity and training provision. The 2020 COVID-19 pandemic has brought to the forefront a need for the scientific community to work even more cooperatively to effectively tackle a global health crisis. EMBL-EBI

AbstractMoonProt 3.0 (http://moonlightingproteins.org) is an updated open-access database storing expert-curated annotations for moonlighting proteins. Moonlighting proteins have two or more physiologically relevant distinct biochemical or biophysical functions performed by a single polypeptide chain. Here, we describe an expansion in the database since our previous report in the Database Issue of

AbstractThree-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due

AbstractGenome-wide association studies have provided a vast array of publicly available SNP × phenotype association results. However, they are often in disparate repositories and formats, making downstream analyses difficult and time consuming. PheLiGe (https://phelige.com) is a database that provides easy access to such results via a web interface. The underlying database currently stores >75 billion

AbstractComparative genomics is the analysis of genomic relationships among different species and serves as a significant base for evolutionary and functional genomic studies. GreenPhylDB (https://www.greenphyl.org) is a database designed to facilitate the exploration of gene families and homologous relationships among plant genomes, including staple crops critically important for global food security

AbstractThe aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce

AbstractCATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally

AbstractCellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein–protein interactions are particularly important due to their versatility, specificity and adaptability. The STRING database aims to integrate all known and predicted associations between proteins, including both physical interactions as well as functional associations. To

AbstractThe Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to users through a straightforward search interface

AbstractThe RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). Protein tandem repeats are ubiquitous in all branches of the tree of life. The accumulation of solved repeat structures provides new possibilities for classification and detection, but also increasing the need for annotation. Here

AbstractThe MobiDB database (URL: https://mobidb.org/) provides predictions and annotations for intrinsically disordered proteins. Here, we report recent developments implemented in MobiDB version 4, regarding the database format, with novel types of annotations and an improved update process. The new website includes a re-designed user interface, a more effective search engine and advanced API for

AbstractThe Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease

AbstractThe Gene Transcription Regulation Database (GTRD; http://gtrd.biouml.org/) contains uniformly annotated and processed NGS data related to gene transcription regulation: ChIP-seq, ChIP-exo, DNase-seq, MNase-seq, ATAC-seq and RNA-seq. With the latest release, the database has reached a new level of data integration. All cell types (cell lines and tissues) presented in the GTRD were arranged into

AbstractProtein–protein interactions (PPIs) are crucial to mediate biological functions, and understanding PPIs in cancer type-specific context could help decipher the underlying molecular mechanisms of tumorigenesis and identify potential therapeutic options. Therefore, we update the Protein Interaction Network Analysis (PINA) platform to version 3.0, to integrate the unified human interactome with

AbstractMetagenomics became a standard strategy to comprehend the functional potential of microbial communities, including the human microbiome. Currently, the number of metagenomes in public repositories is increasing exponentially. The Sequence Read Archive (SRA) and the MG-RAST are the two main repositories for metagenomic data. These databases allow scientists to reanalyze samples and explore new

AbstractLong non-coding RNAs (lncRNAs) play important functional roles in many diverse biological processes. However, not all expressed lncRNAs are functional. Thus, it is necessary to manually collect all experimentally validated functional lncRNAs (EVlncRNA) with their sequences, structures, and functions annotated in a central database. The first release of such a database (EVLncRNAs) was made using

AbstractFor more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. As the field of genomics grows and more data become available, new modes of display are required to accommodate new technologies. New features released this past year include a Hi-C heatmap display, a phased

AbstractIntegration analysis of multi-omics data provides a comprehensive landscape for understanding biological systems and mechanisms. The abundance of high-quality multi-omics data (genomics, transcriptomics, methylomics and phenomics) for the model organism Arabidopsis thaliana enables scientists to study the genetic mechanism of many biological processes. However, no resource is available to provide

AbstractWithin the tumour microenvironment, cells exhibit different behaviours driven by fine-tuning of gene regulation. Identification of cellular-specific gene regulatory networks will deepen the understanding of disease pathology at single-cell resolution and contribute to the development of precision medicine. Here, we describe a database, LnCeCell (http://www.bio-bigdata.net/LnCeCell/ or http://bio-bigdata

AbstractFlyBase (flybase.org) is an essential online database for researchers using Drosophila melanogaster as a model organism, facilitating access to a diverse array of information that includes genetic, molecular, genomic and reagent resources. Here, we describe the introduction of several new features at FlyBase, including Pathway Reports, paralog information, disease models based on orthology

Nucleic Acids Research, gkaa918, https://doi.org/10.1093/nar/gkaa918

AbstractAn updated Lnc2Cancer 3.0 (http://www.bio-bigdata.net/lnc2cancer or http://bio-bigdata.hrbmu.edu.cn/lnc2cancer) database, which includes comprehensive data on experimentally supported long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) associated with human cancers. In addition, web tools for analyzing lncRNA expression by high-throughput RNA sequencing (RNA-seq) and single-cell RNA-seq

AbstractcanSAR (http://cansar.icr.ac.uk) is the largest, public, freely available, integrative translational research and drug discovery knowledgebase for oncology. canSAR integrates vast multidisciplinary data from across genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and more. It also provides unique data, curation and annotation and crucially

AbstractWe describe an updated comprehensive database, LincSNP 3.0 (http://bioinfo.hrbmu.edu.cn/LincSNP), which aims to document and annotate disease or phenotype-associated variants in human long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) or their regulatory elements. LincSNP 3.0 has updated with several novel features, including (i) more types of variants including single nucleotide polymorphisms

AbstractRfam is a database of RNA families where each of the 3444 families is represented by a multiple sequence alignment of known RNA sequences and a covariance model that can be used to search for additional members of the family. Recent developments have involved expert collaborations to improve the quality and coverage of Rfam data, focusing on microRNAs, viral and bacterial RNAs. We have completed

AbstractArrayExpress (https://www.ebi.ac.uk/arrayexpress) is an archive of functional genomics data at EMBL-EBI, established in 2002, initially as an archive for publication-related microarray data and was later extended to accept sequencing-based data. Over the last decade an increasing share of biological experiments involve multiple technologies assaying different biological modalities, such as

AbstractDuring the past decade, genome-wide association studies (GWAS) have identified many genetic variants with susceptibility to several thousands of complex diseases or traits. The genetic regulation of gene expression is highly tissue-specific and cell type-specific. Recently, single-cell technology has paved the way to dissect cellular heterogeneity in human tissues. Here, we present a reference

AbstractWikiPathways (https://www.wikipathways.org) is a biological pathway database known for its collaborative nature and open science approaches. With the core idea of the scientific community developing and curating biological knowledge in pathway models, WikiPathways lowers all barriers for accessing and using its content. Increasingly more content creators, initiatives, projects and tools have

AbstractThe Functional ANnoTation Of the Mammalian genome (FANTOM) Consortium has continued to provide extensive resources in the pursuit of understanding the transcriptome, and transcriptional regulation, of mammalian genomes for the last 20 years. To share these resources with the research community, the FANTOM web-interfaces and databases are being regularly updated, enhanced and expanded with new

AbstractThe BRENDA enzyme database (https://www.brenda-enzymes.org), established in 1987, has evolved into the main collection of functional enzyme and metabolism data. In 2018, BRENDA was selected as an ELIXIR Core Data Resource. BRENDA provides reliable data, continuous curation and updates of classified enzymes, and the integration of newly discovered enzymes. The main part contains >5 million data

AbstractThe Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), the US data center for the global PDB archive and a founding member of the Worldwide Protein Data Bank partnership, serves tens of thousands of data depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without restrictions to millions of RCSB.org users

AbstractCellMiner Cross-Database (CellMinerCDB, discover.nci.nih.gov/cellminercdb) allows integration and analysis of molecular and pharmacological data within and across cancer cell line datasets from the National Cancer Institute (NCI), Broad Institute, Sanger/MGH and MD Anderson Cancer Center (MDACC). We present CellMinerCDB 1.2 with updates to datasets from NCI-60, Broad Cancer Cell Line Encyclopedia

AbstractRNA–protein complexes have emerged as central players in numerous key cellular processes with significant relevance in health and disease. To further deepen our knowledge of RNA-binding proteins (RBPs), multiple proteome-wide strategies have been developed to identify RBPs in different species leading to a large number of studies contributing experimentally identified as well as predicted RBP

AbstractNONCODE (http://www.noncode.org/) is a comprehensive database of collection and annotation of noncoding RNAs, especially long non-coding RNAs (lncRNAs) in animals. NONCODEV6 is dedicated to providing the full scope of lncRNAs across plants and animals. The number of lncRNAs in NONCODEV6 has increased from 548 640 to 644 510 since the last update in 2017. The number of human lncRNAs has increased

AbstractProThermDB is an updated version of the thermodynamic database for proteins and mutants (ProTherm), which has ∼31 500 data on protein stability, an increase of 84% from the previous version. It contains several thermodynamic parameters such as melting temperature, free energy obtained with thermal and denaturant denaturation, enthalpy change and heat capacity change along with experimental

AbstractOrthoDB provides evolutionary and functional annotations of orthologs, inferred for a vast number of available organisms. OrthoDB is leading in the coverage and genomic diversity sampling of Eukaryotes, Prokaryotes and Viruses, and the sampling of Bacteria is further set to increase three-fold. The user interface has been enhanced in response to the massive growth in data. OrthoDB provides

AbstractGenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public database that contains 9.9 trillion base pairs from over 2.1 billion nucleotide sequences for 478 000 formally described species. Daily data exchange with the European Nucleotide Archive and the DNA Data Bank of Japan ensures worldwide coverage. Recent updates include new resources for data from the SARS-CoV-2 virus

AbstractThe Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve

AbstractThe development of new drugs for diseases is a time-consuming, costly and risky process. In recent years, many drugs could be approved for other indications. This repurposing process allows to effectively reduce development costs, time and, ultimately, save patients’ lives. During the ongoing COVID-19 pandemic, drug repositioning has gained widespread attention as a fast opportunity to find

AbstractSplicing is an essential step of RNA processing for multi-exon genes, in which introns are removed from a precursor RNA, thereby producing mature RNAs containing splice junctions. Here, we develope the RJunBase (www.RJunBase.org), a web-accessible database of three types of RNA splice junctions (linear, back-splice, and fusion junctions) that are derived from RNA-seq data of non-cancerous and

AbstractCancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors