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• W4381887729 abstract "Sequence annotation plays a crucial role in bioinformatics, and relies on large-scale sequence database searches with sequence alignment tools. The accuracy of sequence alignment tools depends on their ability to differentiate between true homology and similarity due to random or biased processes. Tool developers rely on benchmarks to evaluate accuracy; these benchmarks consist of trusted homologs for measuring sensitivity and some form of decoy sequences for measuring false labeling. Various methods exist for producing decoys, including shuffling and random sampling; however, these methods may underestimate the rate of false positives by disregarding sources of bias often found in biological sequences. An alternative approach is the use of reversed biological sequences as decoys, because these preserve the distribution of letters and the existence of tandem repeats, while disrupting the original sequence’s functional properties. However, even randomly shuffled sequences contain palindromic elements that are on average longer than the longest common substrings shared between shuffled variants of the same sequence, leading to concerns that reversed sequences may retain signal of homology that has been thought to be destroyed during reversal. Motivated by concerns that this may cause the false positive rate of sequence annotation tools to be overestimated by benchmarks containing reversed sequences, we investigate the effect of reversal on sequence alignment score. We demonstrate that alignment between sequences and their reversals, even shuffled sequences with no notable repetitive or low-complexity regions, produces higher scores than alignment between truly unrelated sequences. We further demonstrate that this elevated score of alignment to reversals holds true even when the reversed sequences are subjected to moderate levels of mutation. As a result of these observations, we counsel against using reversed sequences as false-annotation benchmarks for sequence database search tools." @default.
• W4381887729 created "2023-06-25" @default.
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• W4381887729 date "2023-06-22" @default.
• W4381887729 modified "2023-10-18" @default.
• W4381887729 title "WAS IT A MATch I SAW? Approximate palindromes lead to overstated false match rates in benchmarks using reversed sequences" @default.
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• W4381887729 doi "https://doi.org/10.1101/2023.06.19.545636" @default.
• W4381887729 hasPublicationYear "2023" @default.
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