PatternHunter is a commercially available homology search instrument software that uses sequence alignment techniques. It was initially developed in the year 2002 by three scientists: Bin Ma, John Tramp and Ming Li. [1] :440 These scientists were driven by the desire to solve the problem that many investigators face during studies that involve genomics and proteomics. These scientists realized that such studies greatly relied on homology studies that established short seed matches that were subsequently lengthened. Describing homologous genes was an essential part of most evolutionary studies and was crucial to the understanding of the evolution of gene families, the relationship between domains and families. [2] :7 Homologous genes could only be studied effectively using search tools that established like portions or local placement between two proteins or nucleic acid sequences. [3] :15 Homology was quantified by scores obtained from matching sequences, “mismatch and gap scores”. [4] :164
In comparative genomics, for example, it is necessary to compare huge chromosomes such as those found in the human genome. However, the immense expansion of genomic data introduces a predicament in the available methods of carrying out homology searches. For instance, enlarging the seed size lowers sensitivity while reducing seed size reduces the speed of calculations. Several sequence alignment programs have been developed to determine homology between genes. These include FASTA, the BLAST family, QUASAR, MUMmer, SENSEI, SIM, and REPuter. [1] :440 They mostly use Smith-Waterman alignment technique, which compares bases against other bases, but is too slow. BLAST makes an improvement to this technique by establishing brief, precise seed matches that it later joins up to form longer alignments. [5] :737 However, when dealing with lengthy sequences, the above-mentioned techniques are extremely sluggish and required considerable memory sizes. SENSEI, however, is more efficient than the other methods, but is incompetent in other forms of alignment as its strength lies in handling ungapped alignments. The quality of the production from Megablast, on the other hand, is of poor quality and does not adapt well to large sequences. Techniques such as MUMmer and QUASAR employ suffix trees, which are supposed to handle exact matches. However, these methods can only apply to the comparison of sequences that display elevated similarities. All the above-mentioned problems necessitate the development of a fast reliable tool that can handle all types of sequences efficiently without consuming too many resources in a computer.
PatternHunter utilizes numerous seeds (tiny search strings) with optimal intervals between them. Searches that employ seeds are extremely fast because they only determine homology in places where hits are established. The sensitivity of a search string is greatly influenced by the amount of space between adjacent strings. Large seeds are unable to find isolated homologies, whereas small ones generate numerous arbitrary hits that delay computation. PatternHunter strikes a delicate balance in this area by providing optimal spacing between search strings. It uses alternate k (k = 11) letters as seeds in contrast with BLAST, which utilizes successive k letters as seeds. The first stage in PatternHunter analysis entails a filtering phase where the program hunts for matches in k alternating points as denoted by the most advantageous pattern. [6] :11 The second stage is the alignment phase, which is identical to BLAST. In addition, it is possible to use more than one seed at a go with PatternHunter. This elevates the sensitivity of the tool without interfering with its speed.
PatternHunter takes a short time to analyze all types of sequences. On a modern computer, it can take a few seconds to handle prokaryotic genomes, minutes to process Arabidopsis thaliana sequences and several hours to process a human chromosome. [1] :440 When compared to other tools, PatternHunter exhibits speeds that are approximately a hundred times faster than BLAST and Mega BLAST. [7] These speeds are 3000-fold those attained from a Smith-Waterman algorithm. In addition, the program has a user-friendly interface that allows one to customize the search parameters.
In terms of sensitivity, it is possible to attain the optimum sensitivity with PatternHunter while still retaining the same speed as a conventional BLAST search.
The designing of PatternHunter uses Java technology. Consequently, the program runs smoothly when installed in any Java 1.4 environments. [7]
Homology search is a very lengthy procedure that requires a lot of time. Challenges still remain in handling DNA-DNA searches as well as translated DNA-protein searches because of the vast sizes of databases and the tiny query that is used. PatternHunter has been improved to an upgraded PatternHunter II version, which hastens DNA-protein searches a hundredfold without altering the sensitivity. However, there are plans to improve PatternHunter to attain the high sensitivity of the Smith - Waterman tool while obtaining BLAST pace. A novel translated PatternHunter that intends to hasten tBLASTx. [4] :174 is also in the developmental stages.
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 combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret the biological data. Bioinformatics has been used for in silico analyses of biological queries using mathematical and statistical techniques.
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 in 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). The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper.
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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 library sequences that resemble the query sequence above a certain threshold.
In bioinformatics, sequence clustering algorithms attempt to group biological sequences that are somehow related. The sequences can be either of genomic, "transcriptomic" (ESTs) or protein origin. For proteins, homologous sequences are typically grouped into families. For EST data, clustering is important to group sequences originating from the same gene before the ESTs are assembled to reconstruct the original mRNA.
BioJava is an open-source software project dedicated to provide Java tools to process biological data. BioJava is a set of library functions written in the programming language Java for manipulating sequences, protein structures, file parsers, Common Object Request Broker Architecture (CORBA) interoperability, Distributed Annotation System (DAS), access to AceDB, dynamic programming, and simple statistical routines. BioJava supports a huge range of data, starting from DNA and protein sequences to the level of 3D protein structures. The BioJava libraries are useful for automating many daily and mundane bioinformatics tasks such as to parsing a Protein Data Bank (PDB) file, interacting with Jmol and many more. This application programming interface (API) provides various file parsers, data models and algorithms to facilitate working with the standard data formats and enables rapid application development and analysis.
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FASTA is a DNA and protein sequence alignment software package first described by David J. Lipman and William R. Pearson in 1985. Its legacy is the FASTA format which is now ubiquitous in bioinformatics.
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A multiple sequence alignment (MSA) is a sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. In many cases, the input set of query sequences are assumed to have an evolutionary relationship by which they share a linkage and are descended from a common ancestor. From the resulting MSA, sequence homology can be inferred and phylogenetic analysis can be conducted to assess the sequences' shared evolutionary origins. Visual depictions of the alignment as in the image at right illustrate mutation events such as point mutations that appear as differing characters in a single alignment column, and insertion or deletion mutations that appear as hyphens in one or more of the sequences in the alignment. Multiple sequence alignment is often used to assess sequence conservation of protein domains, tertiary and secondary structures, and even individual amino acids or nucleotides.
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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 Mac OS.
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