Kay Hofmann, MEMOREC Stoffel GmbH, Cologne, Germany
Published online: September 2005
DOI: 10.1038/npg.els.0005259
A profile is a computational representation of sequence properties derived from a family of related proteins. Analogous to single sequences, profiles can be used for database searches using a dynamic programming algorithm. Because profiles allow position-specific scoring systems and gap parameters, profile searches offer a greatly increased sensitivity in detecting distant protein relationships.
Keywords: sequence analysis; alignment; evolutionary distance; homology; statistical significance
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Figure 1. Short sample profile, in generalized profile format: (a) small sample alignment of seven sequences with four residues each; (b) generalized profile derived from the alignment in (a). The lines starting with ‘/M’ contain the actual profile data; the other lines contain additional information such as the alphabet used, default gap parameters and normalization parameters.
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Figure 2. Representation of the iterative refinement process.
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| References | |
| Apweiler R, Attwood TK, Bairoch A, et al. (2001) The InterPro database, an integrated documentation resource for protein families, domains and functional sites. Nucleic Acids Research 29: 37–40. | |
| Baldi P, Chauvin Y, Hunkapiller T and McClure MA (1994) Hidden Markov models of biological primary sequence information. Proceedings of the National Academy of Sciences of the United States of America 91: 1059–1063. | |
| Bucher P and Bairoch A (1994) A generalized profile syntax for biomolecular sequence motifs and its function in automatic sequence interpretation. International Conference on Intelligent Systems for Molecular Biology 2: 53–61. | |
| Bucher P, Karplus K, Moeri N and Hofmann K (1996) A flexible motif search technique based on generalized profiles. Computers and Chemistry 20: 3–23. | |
| Gribskov M, McLachlan AD and Eisenberg D (1987) Profile analysis: detection of distantly related proteins. Proceedings of the National Academy of Sciences of the United States of America 84: 4355–4358. | |
| Henikoff S and Henikoff JG (1993) Performance evaluation of amino acid substitution matrices. Proteins 17: 49–61. | |
| Hofmann K (2000) Sensitive protein comparisons with profiles and Hidden Markov models. Briefings in Bioinformatics 1: 167–179. | |
| Krogh A, Brown M, Mian IS, Sjolander K and Haussler D (1994) Hidden Markov models in computational biology: applications to protein modeling. Journal of Molecular Biology 235: 1501–1531. | |
| Luthy R, Xenarios I and Bucher P (1994) Improving the sensitivity of the sequence profile method. Protein Science: A Publication of the Protein Society 3: 139–146. | |
| Smith TF and Waterman MS (1981) Identification of common molecular subsequences. Journal of Molecular Biology 147: 195–197. | |
| Thompson JD, Higgins DG and Gibson TJ (1994) Improved sensitivity of profile searches through the use of sequence weights and gap excision. Computer Applications in the Biosciences: CABIOS 10: 19–29. | |
| Further Reading | |
| Agarwal P and States DJ (1998) Comparative accuracy of methods for protein sequence similarity search. Bioinformatics 14: 40–47. | |
| Attwood TK (2000) The role of pattern databases in sequence analysis. Briefings in Bioinformatics 1: 45–59. | |
| Birney E, Thompson JD and Gibson TJ (1996) PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames. Nucleic Acids Research 24: 2730–2739. | |
| Bork P and Gibson TJ (1996) Applying motif and profile searches. Methods in Enzymology 266: 162–184. | |
| Doolittle RF (1994) Protein sequence comparisons: searching databases and aligning sequences. Current Opinion in Biotechnology 5: 24–28. | |
| Eddy SR (1998) Profile hidden Markov models. Bioinformatics 14: 755–763. | |
| Hofmann K (1998) Protein classification & functional assignment. Bioinformatics: A Trends Guide 5: 18–21. | |
| Mott R and Tribe R (1999) Approximate statistics of gapped alignments. Journal of Computational Biology: A Journal of Computational Molecular Cell Biology 6: 91–112. | |
| Tatusov RL, Altschul SF and Koonin EV (1994) Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks. Proceedings of the National Academy of Sciences of the United States of America 91: 12091–12095. | |
| Vingron M and Waterman MS (1994) Sequence alignment and penalty choice: review of concepts, case studies and implications. Journal of Molecular Biology 235: 1–12. | |
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