Repeat or not repeat?—Statistical validation of tandem repeat prediction in genomic sequences
Open Access
- 24 August 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 40 (20), 10005-10017
- https://doi.org/10.1093/nar/gks726
Abstract
Tandem repeats (TRs) represent one of the most prevalent features of genomic sequences. Due to their abundance and functional significance, a plethora of detection tools has been devised over the last two decades. Despite the longstanding interest, TR detection is still not resolved. Our large-scale tests reveal that current detectors produce different, often nonoverlapping inferences, reflecting characteristics of the underlying algorithms rather than the true distribution of TRs in genomic data. Our simulations show that the power of detecting TRs depends on the degree of their divergence, and repeat characteristics such as the length of the minimal repeat unit and their number in tandem. To reconcile the diverse predictions of current algorithms, we propose and evaluate several statistical criteria for measuring the quality of predicted repeat units. In particular, we propose a model-based phylogenetic classifier, entailing a maximum-likelihood estimation of the repeat divergence. Applied in conjunction with the state of the art detectors, our statistical classification scheme for inferred repeats allows to filter out false-positive predictions. Since different algorithms appear to specialize at predicting TRs with certain properties, we advise applying multiple detectors with subsequent filtering to obtain the most complete set of genuine repeats.Keywords
This publication has 53 references indexed in Scilit:
- ALF—A Simulation Framework for Genome EvolutionMolecular Biology and Evolution, 2011
- NTRFinder: a software tool to find nested tandem repeatsNucleic Acids Research, 2011
- Ensembl 2011Nucleic Acids Research, 2010
- TRedD--A database for tandem repeats over the edit distanceDatabase: The Journal of Biological Databases and Curation, 2010
- INDELible: A Flexible Simulator of Biological Sequence EvolutionMolecular Biology and Evolution, 2009
- An Improved General Amino Acid Replacement MatrixMolecular Biology and Evolution, 2008
- Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminaseNature Immunology, 2007
- Detecting microsatellites within genomes: significant variation among algorithmsBMC Bioinformatics, 2007
- Role of SGT1 in resistance protein accumulation in plant immunityThe EMBO Journal, 2006
- A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequencesJournal of Molecular Evolution, 1980