PairWise and SearchWise: Finding the Optimal Alignment in a Simultaneous Comparison of a Protein Profile against All DNA Translation Frames

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Abstract
DNA translation frames can be disrupted for several reasons, including: (i) errors in sequence determination; (ii) RNA processing, such as intron removal and guide RNA editing; (iii) less commonly, polymerase frameshifting during transcription or ribosomal frameshifting during translation. Frameshifts frequently confound computational activities involving homologous sequences, such as database searches and inferences on structure, function or phylogeny made from multiple alignments. A dynamic alignment algorithm is reported here which compares a protein profile (a residue scoring matrix for one or more aligned sequences) against the three translation frames of a DNA strand, allowing frameshifting. The algorithm has been incorporated into a new package, WiseTools, for comparison of biological sequences. A protein profile can be compared against either a DNA sequence or a protein sequence. The program PairWise may be used interactively for alignment of any two sequence inputs. SearchWise can perform combinations of searches through DNA or protein databases by a protein profile or DNA sequence. Routine application of the programs has revealed a set of database entries with frameshifts caused by errors in sequence determination.