Related Experiment Video
Updated: Jun 17, 2026

Creating and Applying a Reference to Facilitate the Discussion and Classification of Proteins in a Diverse Group
Published on: August 16, 2017
Homologous over-extension: a challenge for iterative similarity searches
Mileidy W Gonzalez1, William R Pearson
1Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
Abstract:
We have characterized a novel type of PSI-BLAST error, homologous over-extension (HOE), using embedded PFAM domain queries on searches against a reference library containing Pfam-annotated UniProt sequences and random synthetic sequences. PSI-BLAST makes two types of errors: alignments to non-homologous regions and HOE alignments that begin in a homologous region, but extend beyond the homology into neighboring sequence regions. When the neighboring sequence region contains a non-homologous domain, PSI-BLAST can incorporate the unrelated sequence into its position specific scoring matrix, which then finds non-homologous proteins with significant expectation values. HOE accounts for the largest fraction of the initial false positive (FP) errors, and the largest fraction of FPs at iteration 5. In searches against complete protein sequences, 5-9% of alignments at iteration 5 are non-homologous. HOE frequently begins in a partial protein domain; when partial domains are removed from the library, HOE errors decrease from 16 to 3% of weighted coverage (hard queries; 35-5% for sampled queries) and no-error searches increase from 2 to 58% weighed coverage (hard; 16-78% sampled). When HOE is reduced by not extending previously found sequences, PSI-BLAST specificity improves 4-8-fold, with little loss in sensitivity.
Related Concept Videos
Homologous Recombination
Homologous Recombination
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Causes of Similarity-Dissimilarity Effect
Evolutionary Relationships through Genome Comparisons
Crossing Over

