In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Aligned sequences of nucleotide or amino acid residues are typically represented as rows within a matrix. Gaps are inserted between the residues so that identical or similar characters are aligned in successive columns. Sequence alignments are also used for non-biological sequences such as calculating the distance cost between strings in a natural language, or to display financial data.
The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is located in Bethesda, Maryland, and was founded in 1988 through legislation sponsored by US Congressman Claude Pepper.
Overpressure is the pressure caused by a shock wave over and above normal atmospheric pressure. The shock wave may be caused by sonic boom or by explosion, and the resulting overpressure receives particular attention when measuring the effects of nuclear weapons or thermobaric bombs.
In bioinformatics, BLAST is an algorithm and program for comparing primary biological sequence information, such as the amino-acid sequences of proteins or the nucleotides of DNA and/or RNA sequences. A BLAST search enables a researcher to compare a subject protein or nucleotide sequence with a library or database of sequences, and identify database sequences that resemble the query sequence above a certain threshold. For example, following the discovery of a previously unknown gene in the mouse, a scientist will typically perform a BLAST search of the human genome to see if humans carry a similar gene; BLAST will identify sequences in the human genome that resemble the mouse gene based on similarity of sequence.
Stephen Frank Altschul is an American mathematician who has designed algorithms that are used in the field of bioinformatics. Altschul is the co-author of the BLAST algorithm used for sequence analysis of proteins and nucleotides.
InterPro is a database of protein families, protein domains and functional sites in which identifiable features found in known proteins can be applied to new protein sequences in order to functionally characterise them.
David J. Lipman is an American biologist who from 1989 to 2017 was the director of the National Center for Biotechnology Information (NCBI) at the National Institutes of Health. NCBI is the home of GenBank, the U.S. node of the International Sequence Database Consortium, and PubMed, one of the most heavily used sites in the world for the search and retrieval of biomedical information. Lipman is one of the original authors of the BLAST sequence alignment program, and a respected figure in bioinformatics. In 2017, he left NCBI and became Chief Science Officer at Impossible Foods.
Homology modeling, also known as comparative modeling of protein, refers to constructing an atomic-resolution model of the "target" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein. Homology modeling relies on the identification of one or more known protein structures likely to resemble the structure of the query sequence, and on the production of a sequence alignment that maps residues in the query sequence to residues in the template sequence. It has been seen that protein structures are more conserved than protein sequences amongst homologues, but sequences falling below a 20% sequence identity can have very different structure.
Webb Colby Miller is an American bioinformatician who is professor in the Department of Biology and the Department of Computer Science and Engineering at The Pennsylvania State University.
BLAT is a pairwise sequence alignment algorithm that was developed by Jim Kent at the University of California Santa Cruz (UCSC) in the early 2000s to assist in the assembly and annotation of the human genome. It was designed primarily to decrease the time needed to align millions of mouse genomic reads and expressed sequence tags against the human genome sequence. The alignment tools of the time were not capable of performing these operations in a manner that would allow a regular update of the human genome assembly. Compared to pre-existing tools, BLAT was ~500 times faster with performing mRNA/DNA alignments and ~50 times faster with protein/protein alignments.
The Protein Structure Initiative (PSI) was a USA based project that aimed at accelerating discovery in structural genomics and contribute to understanding biological function. Funded by the U.S. National Institute of General Medical Sciences (NIGMS) between 2000 and 2015, its aim was to reduce the cost and time required to determine three-dimensional protein structures and to develop techniques for solving challenging problems in structural biology, including membrane proteins. Over a dozen research centers have been supported by the PSI for work in building and maintaining high-throughput structural genomics pipelines, developing computational protein structure prediction methods, organizing and disseminating information generated by the PSI, and applying high-throughput structure determination to study a broad range of important biological and biomedical problems.
HMMER is a free and commonly used software package for sequence analysis written by Sean Eddy. Its general usage is to identify homologous protein or nucleotide sequences, and to perform sequence alignments. It detects homology by comparing a profile-HMM to either a single sequence or a database of sequences. Sequences that score significantly better to the profile-HMM compared to a null model are considered to be homologous to the sequences that were used to construct the profile-HMM. Profile-HMMs are constructed from a multiple sequence alignment in the HMMER package using the hmmbuild program. The profile-HMM implementation used in the HMMER software was based on the work of Krogh and colleagues. HMMER is a console utility ported to every major operating system, including different versions of Linux, Windows, and macOS.
RAPTOR is protein threading software used for protein structure prediction. It has been replaced by RaptorX, which is much more accurate than RAPTOR.
CS-BLAST (Context-Specific BLAST) is a tool that searches a protein sequence that extends BLAST, using context-specific mutation probabilities. More specifically, CS-BLAST derives context-specific amino-acid similarities on each query sequence from short windows on the query sequences. Using CS-BLAST doubles sensitivity and significantly improves alignment quality without a loss of speed in comparison to BLAST. CSI-BLAST is the context-specific analog of PSI-BLAST, which computes the mutation profile with substitution probabilities and mixes it with the query profile. CSI-BLAST is the context specific analog of PSI-BLAST. Both of these programs are available as web-server and are available for free download.
Residue depth (RD) is a solvent exposure measure that describes to what extent a residue is buried in the protein structure space. It complements the information provided by conventional accessible surface area (ASA).
Phyre and Phyre2 are free web-based services for protein structure prediction. Phyre is among the most popular methods for protein structure prediction having been cited over 1,500 times. Like other remote homology recognition techniques, it is able to regularly generate reliable protein models when other widely used methods such as PSI-BLAST cannot. Phyre2 has been designed to ensure a user-friendly interface for users inexpert in protein structure prediction methods. Its development is funded by the Biotechnology and Biological Sciences Research Council.
Swiss-model is a structural bioinformatics web-server dedicated to homology modeling of 3D protein structures. As of 2024, homology modeling is the most accurate method to generate reliable three-dimensional protein structure models and is routinely used in many practical applications. Homology modelling methods make use of experimental protein structures (templates) to build models for evolutionary related proteins (targets).
The HH-suite is an open-source software package for sensitive protein sequence searching. It contains programs that can search for similar protein sequences in protein sequence databases. Sequence searches are a standard tool in modern biology with which the function of unknown proteins can be inferred from the functions of proteins with similar sequences. HHsearch and HHblits are two main programs in the package and the entry point to its search function, the latter being a faster iteration. HHpred is an online server for protein structure prediction that uses homology information from HH-suite.
PredictProtein (PP) is an automatic service that searches up-to-date public sequence databases, creates alignments, and predicts aspects of protein structure and function. Users send a protein sequence and receive a single file with results from database comparisons and prediction methods. PP went online in 1992 at the European Molecular Biology Laboratory; since 1999 it has operated from Columbia University and in 2009 it moved to the Technische Universität München. Although many servers have implemented particular aspects, PP remains the most widely used public server for structure prediction: over 1.5 million requests from users in 104 countries have been handled; over 13000 users submitted 10 or more different queries. PP web pages are mirrored in 17 countries on 4 continents. The system is optimized to meet the demands of experimentalists not experienced in bioinformatics. This implied that we focused on incorporating only high-quality methods, and tried to collate results omitting less reliable or less important ones.
