De novo identification of highly diverged protein repeats by probabilistic consistency.
BACKGROUND
An estimated 25% of all eukaryotic proteins contain repeats, which underlines the importance of duplication for evolving new protein functions. Internal repeats often correspond to structural or functional units in proteins. Methods capable of identifying diverged repeated segments or domains at the sequence level can therefore assist in predicting domain structures, inferring hypotheses about function and mechanism, and investigating the evolution of proteins from smaller fragments.


RESULTS
We present HHrepID, a method for the de novo identification of repeats in protein sequences. It is able to detect the sequence signature of structural repeats in many proteins that have not yet been known to possess internal sequence symmetry, such as outer membrane beta-barrels. HHrepID uses HMM-HMM comparison to exploit evolutionary information in the form of multiple sequence alignments of homologs. In contrast to a previous method, the new method (1) generates a multiple alignment of repeats; (2) utilizes the transitive nature of homology through a novel merging procedure with fully probabilistic treatment of alignments; (3) improves alignment quality through an algorithm that maximizes the expected accuracy; (4) is able to identify different kinds of repeats within complex architectures by a probabilistic domain boundary detection method and (5) improves sensitivity through a new approach to assess statistical significance.


BACKGROUND
Server: http://toolkit.tuebingen.mpg.de/hhrepid; Executables: ftp://ftp.tuebingen.mpg.de/pub/protevo/HHrepID
Biegert
A
A
Department for Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstr. 35, 72076 Tübingen, Germany.
Söding
J
J
D000465:Algorithms; D000595:Amino Acid Sequence; D003627:Data Interpretation, Statistical; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*; D020449:Repetitive Sequences, Amino Acid; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software
D011506:Proteins