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Bioinformatics, Vol 14, 846-856, Copyright © 1998 by Oxford University Press


ARTICLES

Hidden Markov models for detecting remote protein homologies

K Karplus, C Barrett and R Hughey
Department of Computer Engineering, Jack Baskin School of Engineering, University of California, Santa Cruz, CA 95064, USA.

MOTIVATION: A new hidden Markov model method (SAM-T98) for finding remote homologs of protein sequences is described and evaluated. The method begins with a single target sequence and iteratively builds a hidden Markov model (HMM) from the sequence and homologs found using the HMM for database search. SAM-T98 is also used to construct model libraries automatically from sequences in structural databases. METHODS: We evaluate the SAM-T98 method with four datasets. Three of the test sets are fold-recognition tests, where the correct answers are determined by structural similarity. The fourth uses a curated database. The method is compared against WU-BLASTP and against DOUBLE- BLAST, a two-step method similar to ISS, but using BLAST instead of FASTA. RESULTS: SAM-T98 had the fewest errors in all tests-dramatically so for the fold-recognition tests. At the minimum-error point on the SCOP (Structural Classification of Proteins)-domains test, SAM-T98 got 880 true positives and 68 false positives, DOUBLE-BLAST got 533 true positives with 71 false positives, and WU-BLASTP got 353 true positives with 24 false positives. The method is optimized to recognize superfamilies, and would require parameter adjustment to be used to find family or fold relationships. One key to the performance of the HMM method is a new score-normalization technique that compares the score to the score with a reversed model rather than to a uniform null model. AVAILABILITY: A World Wide Web server, as well as information on obtaining the Sequence Alignment and Modeling (SAM) software suite, can be found at http://www.cse.ucsc.edu/research/compbi o/ CONTACT: karplus@cse.ucsc.edu; http://www.cse.ucsc.edu/~karplus
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Protein Eng. Des. Sel., November 1, 2003; 16(11): 819 - 829.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
E. Gherardi, M. E. Youles, R. N. Miguel, T. L. Blundell, L. Iamele, J. Gough, A. Bandyopadhyay, G. Hartmann, and P. J. G. Butler
Functional map and domain structure of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor
PNAS, October 14, 2003; 100(21): 12039 - 12044.
[Abstract] [Full Text] [PDF]


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Genome ResHome page
P. D. Thomas, M. J. Campbell, A. Kejariwal, H. Mi, B. Karlak, R. Daverman, K. Diemer, A. Muruganujan, and A. Narechania
PANTHER: A Library of Protein Families and Subfamilies Indexed by Function
Genome Res., September 1, 2003; 13(9): 2129 - 2141.
[Abstract] [Full Text] [PDF]


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MycologiaHome page
I. Schmitt, H. T. Lumbsch, and U. Sochting
Phylogeny of the lichen genus Placopsis and its allies based on Bayesian analyses of nuclear and mitochondrial sequences
Mycologia, September 1, 2003; 95(5): 827 - 835.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
I. Rigoutsos, P. Riek, R. M. Graham, and J. Novotny
Structural details (kinks and non-{alpha} conformations) in transmembrane helices are intrahelically determined and can be predicted by sequence pattern descriptors
Nucleic Acids Res., August 1, 2003; 31(15): 4625 - 4631.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
B. John and A. Sali
Comparative protein structure modeling by iterative alignment, model building and model assessment
Nucleic Acids Res., July 15, 2003; 31(14): 3982 - 3992.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
V. A. Eyrich and B. Rost
META-PP: single interface to crucial prediction servers
Nucleic Acids Res., July 1, 2003; 31(13): 3308 - 3310.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
I. Y. Y. Koh, V. A. Eyrich, M. A. Marti-Renom, D. Przybylski, M. S. Madhusudhan, N. Eswar, O. Grana, F. Pazos, A. Valencia, A. Sali, et al.
EVA: evaluation of protein structure prediction servers
Nucleic Acids Res., July 1, 2003; 31(13): 3311 - 3315.
[Abstract] [Full Text] [PDF]


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Protein Eng Des SelHome page
M. Albrecht, S. C.E. Tosatto, T. Lengauer, and G. Valle
Simple consensus procedures are effective and sufficient in secondary structure prediction
Protein Eng. Des. Sel., July 1, 2003; 16(7): 459 - 462.
[Abstract] [Full Text] [PDF]


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Hum Mol GenetHome page
T. S. Furey and D. Haussler
Integration of the cytogenetic map with the draft human genome sequence
Hum. Mol. Genet., May 1, 2003; 12(9): 1037 - 1044.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
B. Cooper, J. D. Clarke, P. Budworth, J. Kreps, D. Hutchison, S. Park, S. Guimil, M. Dunn, P. Luginbuhl, C. Ellero, et al.
A network of rice genes associated with stress response and seed development
PNAS, April 15, 2003; 100(8): 4945 - 4950.
[Abstract] [Full Text] [PDF]


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Protein Eng Des SelHome page
D. Fischer and L. Rychlewski
The 2002 Olympic Games of Protein Structure Prediction
Protein Eng. Des. Sel., March 1, 2003; 16(3): 157 - 160.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
A. Cronin, S. Mowbray, H. Durk, S. Homburg, I. Fleming, B. Fisslthaler, F. Oesch, and M. Arand
The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase
PNAS, February 18, 2003; 100(4): 1552 - 1557.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
M. Madan Babu and S. A. Teichmann
Evolution of transcription factors and the gene regulatory network in Escherichia coli
Nucleic Acids Res., February 15, 2003; 31(4): 1234 - 1244.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
B. M. Swalla, R. I. Gumport, and J. F. Gardner
Conservation of structure and function among tyrosine recombinases: homology-based modeling of the lambda integrase core-binding domain
Nucleic Acids Res., February 1, 2003; 31(3): 805 - 818.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
F. M. G. Pearl, C. F. Bennett, J. E. Bray, A. P. Harrison, N. Martin, A. Shepherd, I. Sillitoe, J. Thornton, and C. A. Orengo
The CATH database: an extended protein family resource for structural and functional genomics
Nucleic Acids Res., January 1, 2003; 31(1): 452 - 455.
[Abstract] [Full Text] [PDF]



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