Databases are a major component of bioinformatics, with various databases covering almost all fields of life sciences. Nucleic acid sequence databases include GenBank, EMBL, DDB, etc.; protein sequence databases include SWISS-PROT, PIR, OWL, NRL3D, TrEMBL, etc.; protein fragment databases include PROSITE, BLOCKS, PRINTS, etc.; three-dimensional structure databases include PDB, NDB, BioMagResBank, CCSD, etc.; databases related to protein structure include SCOP, CATH, FSSP, 3D-ALI, DSSP, etc.; genome-related databases include ESTdb, OMIM, GDB, GSDB, etc.; literature databases include Medline, Uncover, etc. Additionally, some companies have developed commercial databases, such as MDL. Bioinformatics databases are extensive, dispersed, and have non-uniform formats, leading some bio-computing centers to integrate multiple databases to provide comprehensive services, such as EBI’s SRS (Sequence Retrieval System), which includes over 30 databases such as nucleic acid sequence libraries, protein sequence libraries, and three-dimensional structure libraries, along with powerful search tools like CLUSTALW and PROSITESEARCH, allowing users to perform various queries across multiple databases. Below is a brief introduction to some well-known and distinctive biological information databases. Gene and Genome Databases 1. GenBank Database
The GenBank database contains all known nucleic acid sequences and protein sequences, as well as the literature and biological annotations associated with them. It is established and maintained by the National Center for Biotechnology Information (NCBI) in the United States. Its data comes directly from sequences submitted by sequencing workers; a large number of EST sequences and other sequencing data submitted by sequencing centers; and data exchanged in collaboration with other data agencies. GenBank exchanges data daily with the European Molecular Biology Laboratory (EMBL) database and Japan’s DNA Data Bank (DDBJ), synchronizing data among these three databases. GenBank data can be downloaded for free from NCBI’s FTP server, either as a complete library or as newly accumulated data. NCBI also provides extensive data query, sequence similarity search, and other analysis services, which users can find on NCBI’s homepage.
The data in the GenBank library comes from approximately 55,000 species, of which 56% are human genome sequences (34% of all sequences are human EST sequences). Each GenBank data record contains a brief description of the sequence, its scientific name, species classification name, references, sequence feature table, and the sequence itself. The sequence feature table includes annotations of biological features of the sequence, such as: coding regions, transcription units, repeat regions, mutation sites, or modification sites, etc. All data records are divided into several files, such as bacteria, viruses, primates, rodents, as well as EST data, genomic sequencing data, large-scale genomic sequence data, and other 16 categories, among which EST data is further divided into several files. (1) GenBank Data Retrieval
The database retrieval query system of NCBI is Entrez. Entrez is a web-based integrated bioinformatics database retrieval system. Using the Entrez system, users can conveniently retrieve nucleic acid data from GenBank, as well as protein sequence data, genomic map data from GenBank and other databases, three-dimensional structure data of proteins from the Molecular Model Database (MMDB), population sequence datasets, and literature data obtained from PubMed’s Medline.
Entrez provides convenient and practical retrieval services, and all operations can be completed on a web browser. Users can utilize the features provided on the Entrez interface, such as Limits, Index, History, and Clipboard, to perform complex retrieval queries. For the records obtained from retrieval, users can select the data they need to display, save query results, and even view the retrieved sequences graphically. More detailed instructions for using Entrez can be found on this homepage. (2) Submitting Sequence Data to GenBank
Sequencing workers can submit new sequences obtained from their work to NCBI to add to the GenBank database. This task can be accomplished using the web-based BankIt or the standalone Sequin program. BankIt consists of a series of forms, including contact information, publication requirements, reference citation information, sequence source information, and the sequence itself. After submitting the sequence, users will receive an automatically generated data entry, a new sequence number from GenBank, and a complete data record after annotation via email. Users can also modify the information of already published sequences on the BankIt page. BankIt is suitable for independent sequencing workers submitting a small number of sequences, but is not suitable for submitting large numbers of sequences or very long sequences; EST sequences and GSS sequences should not be submitted via BankIt. Instructions for using BankIt and requirements for sequences can be found on its homepage.
Large numbers of sequence submissions can be completed using the Sequin program. The Sequin program allows for easy editing and processing of complex annotations and includes a series of built-in checks to improve sequence quality assurance. It is also designed for submitting sequences from systematic evolution, population, and mutation studies, and can incorporate alignment data. The Sequin program running on different operating systems can be found at ftp://ncbi.nlm.nih.gov/sequin/; instructions for using Sequin can be found on its webpage.
NCBI website: http://www.ncbi.nlm.nih.gov. Entrez website: http://www.ncbi.nlm.nih.gov/entrez/. BankIt website: http://www.ncbi.nlm.nih.gov/BankIt. Sequin related website: http://www.ncbi.nlm.nih.gov/Sequin/. 2. EMBL Nucleic Acid Sequence Database
The EMBL nucleic acid sequence database is maintained by the European Bioinformatics Institute (EBI) and consists of nucleic acid sequence data. Due to data collaboration and exchange with GenBank and DDBJ, it is also a comprehensive nucleic acid sequence database. This database is managed and maintained by the Oracle database system, and queries can be completed through the Sequence Retrieval System (SRS) service available on the internet. Submitting sequences to the EMBL nucleic acid sequence database can be done using the web-based WEBIN tool or the Sequin software. EMBL database website: http://www.ebi.ac.uk/embl/. SRS website: http://srs.ebi.ac.uk/. WEBIN website: http://www.ebi.ac.uk/embl/Submission/webin.html. 3. DDBJ Database
The DNA Data Bank of Japan (DDBJ) is also a comprehensive nucleic acid sequence database that collaborates with GenBank and EMBL to exchange data. The DDBJ homepage provides an SRS tool for data retrieval and sequence analysis. Sequences can be submitted to this database using the Sequin software. DDBJ website: http://www.ddbj.nig.ac.jp/. 4. GDB
The Genome Database (GDB) preserves and processes genomic map data for the Human Genome Project (HGP). GDB aims to construct an encyclopedia of the human genome; in addition to constructing genomic maps, it has developed methods to describe genomic content at the sequence level, including sequence variations and other descriptions related to function and phenotype. Currently, GDB contains: human genomic regions (including genes, clones, amplimers, PCR markers, breakpoints, cytogenetic markers, fragile sites, EST sequences, syndromic regions, contigs, and repeat sequences); human genomic maps (including cytogenetic maps, linkage maps, radioactive hybridization maps, content contig maps, and comprehensive maps, etc.); variations within the human genome (including mutations and polymorphisms, along with allele frequency data). The GDB database stores data in an object model and provides web-based data object retrieval services, allowing users to search for various types of objects and view genomic maps graphically. GDB website: http://www.gdb.org. GDB domestic mirror website: http://gdb.pku.edu.cn/gdb/. Protein Databases 1. PIR and PSD
The PIR International Protein Sequence Database (PSD) is the largest public protein sequence database maintained collaboratively by the Protein Information Resource (PIR), the Munich Protein Sequence Information Center (MIPS), and the Japanese International Protein Sequence Database (JIPID). It is a comprehensive, annotated, non-redundant protein sequence database that includes protein sequences from dozens of complete genomes. All sequence data has been organized, with over 99% of sequences categorized by protein family, and more than half categorized by protein superfamily. The annotations in PSD also include cross-references to many sequence, structure, genomic, and literature databases, as well as internal indices between entries in the database, which help users conveniently retrieve entries including complexes, enzyme-substrate interactions, activation and regulatory cascades, and entries with common features. A complete database is released quarterly, with weekly updates available.
The PSD database has several auxiliary databases, such as non-redundant libraries based on superfamilies. PIR provides three types of sequence search services: text-based interactive retrieval; standard sequence similarity searches, including BLAST, FASTA, etc.; and advanced searches combining sequence similarity, annotation information, and protein family information, including similarity searches categorized by annotation and domain searches like GeneFIND, etc. The PIR and PSD website: http://pir.georgetown.edu/. Database download link: ftp://nbrfa.georgetown.edu/pir/. 2. SWISS-PROT
SWISS-PROT is an annotated protein sequence database maintained by the European Bioinformatics Institute (EBI). The database consists of protein sequence entries, each containing protein sequences, reference literature information, taxonomic information, annotations, etc. The annotations include information on protein function, post-translational modifications, special sites and regions, secondary structure, quaternary structure, similarity to other sequences, relationships between sequence defects and diseases, sequence variants, and conflicts. SWISS-PROT minimizes redundant sequences as much as possible and has established cross-references with over 30 other databases, including nucleic acid sequence libraries, protein sequence libraries, and protein structure libraries, etc.
The Sequence Retrieval System (SRS) can be conveniently used to retrieve SWISS-PROT and other EBI databases. SWISS-PROT only accepts protein sequences obtained from direct sequencing, and sequence submissions can be completed on its web page. SWISS-PROT website: http://www.ebi.ac.uk/swissprot/. 3. PROSITE
The PROSITE database collects biologically significant protein sites and sequence patterns and can quickly and reliably identify which protein family an unknown functional protein sequence should belong to based on these sites and patterns. In some cases, a protein may have low overall sequence similarity to known functional proteins, but retains sequence patterns closely related to function due to functional requirements, allowing for the discovery of hidden functional motifs through PROSITE searches, making it an effective tool for sequence analysis. The sequence patterns involved in PROSITE include catalytic sites of enzymes, ligand-binding sites, residues that bind to metal ions, cysteines involved in disulfide bonds, regions that bind to small molecules or other proteins, etc.; in addition to sequence patterns, PROSITE also includes profiles constructed from multiple sequence alignments, which can more sensitively detect sequence similarity to profiles. Various related retrieval services are provided on the PROSITE homepage. PROSITE website: http://www.expasy.ch/prosite/. 4. PDB
The Protein Data Bank (PDB) is the only international archive of biological macromolecular structure data, established by the Brookhaven National Laboratory in the United States. The data collected by PDB comes from X-ray crystallography and nuclear magnetic resonance (NMR) data, which are archived after organization and confirmation. Currently, the maintenance of the PDB database is handled by the Research Collaboratory for Structural Bioinformatics (RCSB). The main server of RCSB and mirror servers around the world provide database retrieval and download services, as well as descriptions of PDB data file formats and other documents; PDB data can also be obtained from issued CDs. Software like Rasmol can be used on computers to display the three-dimensional structure of biological macromolecules according to PDB files. RCSB PDB database website: http://www.rcsb.org/pdb/. 5. SCOP
The Structural Classification of Proteins (SCOP) database provides detailed descriptions of the relationships between known protein structures. Classification is based on several levels: families, describing close evolutionary relationships; superfamilies, describing distant evolutionary relationships; folds, describing relationships of spatial geometric structures; and fold classes, where all folds are classified into major categories such as all-alpha, all-beta, alpha/beta, alpha + beta, and multi-domain. SCOP also provides a non-redundant ASTRAIL sequence library, which is often used to evaluate various sequence alignment algorithms. Additionally, SCOP offers a PDB-ISL intermediate sequence library, which can be used to find known structure sequences that are distantly related to unknown structure sequences through pairwise comparisons with sequences in this library. SCOP website: http://scop.mrc-lmb.cam.ac.uk/scop/. 6. COG
The Clusters of Orthologous Groups (COGs) database is constructed by classifying coding proteins from 21 complete genomes of bacteria, algae, and eukaryotes based on their evolutionary relationships. The COG library is useful for predicting the function of individual proteins and the functions of proteins in an entire new genome. Using the COGNITOR program, a protein can be compared with all proteins in the COGs and classified into the appropriate COG cluster. The COG library provides retrieval and query services for COG classification data, web-based COGNITOR services, and evolutionary pattern query services, etc. COG library website: http://www.ncbi.nlm.nih.gov/COG. Downloading the COG library and the COGNITOR program can be done at: ftp://ncbi.nlm.nih.gov/pub/COG. Functional Databases 1. KEGG
The Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions, linking genomic information and functional information. Genomic information is stored in the GENES database, including complete and partially sequenced genomic sequences; more advanced functional information is stored in the PATHWAY database, including illustrated cellular biochemical processes such as metabolism, membrane transport, signal transduction, cell cycle, as well as information on homologous conserved sub-pathways; another KEGG database is LIGAND, which contains information about chemical substances, enzyme molecules, enzyme reactions, etc. KEGG provides a Java graphical tool to access genomic maps, compare genomic maps, and operate expression maps, as well as other sequence comparison, graphical comparison, and pathway computation tools, which can be obtained for free. KEGG website: http://www.genome.ad.jp/kegg/. 2. DIP
The Database of Interacting Proteins (DIP) collects experimentally validated protein-protein interactions. The database includes three parts: information about proteins, information about interactions, and experimental techniques for detecting interactions. Users can query the DIP database based on proteins, biological species, protein superfamilies, keywords, experimental techniques, or cited literature. DIP website: http://dip.doe-mbi.ucla.edu/. 3. ASDB
The Alternative Splicing Database (ASDB) includes both protein and nucleic acid libraries. The ASDB (protein) part comes from the SWISS-PROT protein sequence library, constructed by selecting sequences with alternative splicing annotations, searching for related alternative splicing sequences, and through sequence alignment, screening, and classification. The ASDB (nucleic acid) part comes from complete gene compositions mentioned and annotated in GenBank regarding alternative splicing. The database provides convenient search services. ASDB website: http://cbcg.nersc.gov/asdb. 4. TRRD
The Transcription Regulation Database (TRRD) is constructed based on accumulating information about the structural-functional characteristics of regulatory regions of eukaryotic genes. Each TRRD entry contains various structural-functional characteristics of specific genes: transcription factor binding sites, promoters, enhancers, silencers, and gene expression regulatory patterns, etc. TRRD includes five related data tables: TRRDGENES (containing basic information about all genes in the TRRD database and regulatory unit information); TRRDSITES (including specific information about regulatory factor binding sites); TRRDFACTORS (including specific information about regulatory factors that bind to various sites in the TRRD); TRRDEXP (including specific descriptions of gene expression patterns); TRRDBIB (including all references related to annotations). The TRRD homepage provides retrieval services for these data tables. TRRD website: http://wwwmgs.bionet.nsc.ru/mgs/dbases/trrd4/. 5. TRANSFAC
The TRANSFAC database is about transcription factors, their binding sites on the genome, and profiles of their interactions with DNA. It consists of data tables such as SITE, GENE, FACTOR, CLASS, MATRIX, CELLS, METHOD, and REFERENCE. In addition, there are several extension libraries closely related to TRANSFAC: the PATHODB library collects transcription factors and binding sites that may lead to pathological mutations; the S/MART DB collects information about protein factors and sites related to chromosomal structural changes; the TRANSPATH library is used to describe signaling networks related to transcription factor regulation; the CYTOMER library shows the expression status of human transcription factors in various organs, cell types, physiological systems, and developmental stages. TRANSFAC and its related databases can be downloaded for free and can be queried and searched via the web. TRANSFAC website: http://transfac.gbf.de/TRANSFAC/. Other Database Resources 1. DBCat
DBCat is a directory database of bioinformatics databases, collecting information about over 500 bioinformatics databases and classifying them according to their application fields. This includes basic types such as DNA, RNA, proteins, genomes, maps, protein structures, literature, etc. The database can be downloaded for free or queried online. DBCat website: http://www.infobiogen.fr/services/dbcat/. Downloading DBCat website: ftp://ftp.infobiogen.fr/pub/db/dbcat. 2. PubMed
PubMed is a literature citation database maintained by NCBI, providing citation queries for MEDLINE, Pre-MEDLINE, and links to a large number of online scientific electronic journals. The Entrez system can be used to conveniently query PubMed. PubMed website: http://www.ncbi.nlm.nih.gov/.
In addition to the databases mentioned above, there are many specialized bioinformatics databases covering various aspects and fields of current biological research. Due to space limitations, it is not possible to detail them all. There are also several large database mirror sites and uniquely developed databases in China, and we look forward to more high-quality and user-friendly database resources in the country to promote the development of bioinformatics and the entire life sciences in China.
Please follow the “Kangce Technology” WeChat official account.
