Homologous over-extension: a challenge for iterative similarity searches.

Indeed, for one query set, HOE of the query improved PSI-BLAST performance because the random over-extension allowed a marginally insignificant homolog to score within the statistical threshold.

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Statistical estimates for iterative methods like PSI-BLAST can be much less accurate ( 7 , 8 ); sometimes sequences that are clearly unrelated (they have different three-dimensional topologies) obtain highly significant expectation values (<10 –6 ) that imply clear homology.

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