In the field of
bioinformatics
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
, a sequence database is a type of
biological database
Biological databases are libraries of biological sciences, collected from scientific experiments, published literature, high-throughput experiment technology, and computational analysis. They contain information from research areas including genom ...
that is composed of a large collection of computerized ("
digital
Digital usually refers to something using discrete digits, often binary digits.
Technology and computing Hardware
*Digital electronics, electronic circuits which operate using digital signals
**Digital camera, which captures and stores digital i ...
")
nucleic acid sequence
A nucleic acid sequence is a succession of Nucleobase, bases signified by a series of a set of five different letters that indicate the order of nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. By convention, sequence ...
s,
protein sequence
Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesi ...
s, or other
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
sequences stored on a computer. The
UniProt
UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from ...
database is an example of a
protein sequence
Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesi ...
database. As of 2013 it contained over 40 million sequences and is growing at an exponential rate. Historically, sequences were published in paper form, but as the number of sequences grew, this storage method became unsustainable.
Search
Searching in a sequence database involves looking for similarities between a genomic/protein sequence and a query string and, finding the sequence in the database that "best" matches the target sequence (based on criteria which vary depending on the search method). The number of matches/hits is used to formulate a score that determines the similarity between the sequence query and the sequences in the sequence database. The main goal is to have a good balance between the two criteria.
History
1950
The need for sequence databases originated in 1950 when Fredrick Sanger reported the primary structure of insulin. He won his second Nobel Prize for creating methods for sequencing nucleic acids, and his comparative approach is what sparked other protein biochemists to begin collecting amino acid sequences. Thus marking the beginning of molecular databases.
1960
In 1965 Margaret Dayhoff and her team at the National Biomedical Research Foundation (NBRF) published ''"The Atlas of Protein Sequence and Structure".'' They put all know protein sequences in the ''Atlas'', even unpublished material. This can be seen as the first attempt to create a molecular database. They made use of the newly computerized (1964) Medical Literature Analysis and Retrieval System (MEDLARS) at the National Institutes of Health (NIH). The team used computers to store the data but had to manually type and proofread each sequence, which had a high cost in time and money.
In 1966 the team released the second edition of the ''Atlas,'' double the size of the first. It contained about 1000 sequences, and this time was coined as an information explosion. The National Biomedical Research Foundation (NBRF) was on the cutting edge of utilizing computers for medicine and biology at this time. Dayhoff and her team made use of their facilities for determining amino acid sequences of protein molecules in mainframe computers. The number of discovered sequences continued to grow allowing for a deeper comparative analysis of proteins than ever before. This led to many developments such as, probabilistic models of amino acid substitutions, sequence aligning and phylogenetic trees of evolutionary relationships of proteins.
1970
Entire sequencing process became fully automated.
1980
The first nucleotide sequence database was created. Previously known as the European Molecular Biology Laboratory (EMBL) Nucleotide Sequence Data Library (now known as European Nucleotide archive).
Human Genome Project
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...
began in 1988. The project's goal was sequence and map all the genes in a human which required the capability to create and utilize a large sequence database.
Present Day
We now have many sequence databases, tools for using them and easy access to them. One of the largest being
GenBank
The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a part ...
which contains over 2 billion sequences.
Timeline
Current issues
Storage & Redundancy
Records in sequence databases are deposited from a wide range of sources, from individual researchers to large genome sequencing centers. As a result, the sequences themselves, and especially the biological annotations attached to these sequences, may vary in quality. There is much redundancy, as multiple labs may submit numerous sequences that are identical, or nearly identical, to others in the databases.
Many annotations of the sequences are based not on laboratory experiments, but on the results of sequence similarity searches for previously annotated sequences. Once a sequence has been annotated based on similarity to others, and itself deposited in the database, it can also become the basis for future annotations. This can led to a ''transitive annotation problem'' because there may be several such annotation transfers by sequence similarity between a particular database record and actual
wet lab A wet lab, or experimental lab, is a type of laboratory where it is necessary to handle various types of chemicals and potential "wet" hazards, so the room has to be carefully designed, constructed, and controlled to avoid spillage and contamination ...
experimental information.
Therefore, care must be taken when interpreting the annotation data from sequence databases.
Scoring Methods
Most of the current database search algorithms rank alignment by a score, which is usually a particular scoring system. The solution towards solving this issue is found by making a variety of scoring systems available to suit to the specific problem.
Alignment Statistics
When using a searching algorithm we often produce an ordered list which can often carry a lack of biological significance.
See also
*
FASTA format
In bioinformatics and biochemistry, the FASTA format is a text-based format for representing either nucleotide sequences or amino acid (protein) sequences, in which nucleotides or amino acids are represented using single-letter codes. The format a ...
*
SIMAP
*
List of biological databases
Biological databases are stores of biological information. The journal ''Nucleic Acids Research'' regularly publishes special issues on biological databases and has a list of such databases. The 2018 issue has a list of about 180 such databases an ...
*
Bioinformatics
Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
References
External links
European Bioinformatics Institute databasesNCBI completely sequenced genomesStanford Saccharomyces Genome DatabaseProtein the
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
protein database, a collection of sequences from several sources, including translations from annotated coding regions in
GenBank
The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a part ...
,
RefSeq
The Reference Sequence (RefSeq) database is an open access, annotated and curated collection of publicly available nucleotide sequences ( DNA, RNA) and their protein products. RefSeq was first introduced in 2000. This database is built by National ...
and
TPA, as well as records from
SwissProt
UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from ...
,
PIR, PRF, and
PDB
{{Use dmy dates, date=April 2017
Biotechnology databases