biostudies-otherUnknown18(1)Al-Jaff MBMC bioinformatics228https://www.ebi.ac.uk/biostudies/studies/S-EPMC5414201A common challenge in bioinformatics is to identify short sub-sequences that are unique in a set of genomes or reference sequences, which can efficiently be achieved by k-mer (k consecutive nucleotides) counting. However, there are several areas that would benefit from a more stringent definition of "unique", requiring that these sub-sequences of length W differ by more than k mismatches (i.e. a Hamming distance greater than k) from any other sub-sequence, which we term the k-disjoint problem. Examples include finding sequences unique to a pathogen for probe-based infection diagnostics; reducing off-target hits for re-sequencing or genome editing; detecting sequence (e.g. phage or viral) insertions; and multiple substitution mutations. Since both sensitivity and specificity are critical, an exhaustive, yet efficient solution is desirable.We present microTaboo, a method that allows for efficient and extensive sequence mining of unique (k-disjoint) sequences of up to 100 nucleotides in length. On a number of simulated and real data sets ranging from microbe- to mammalian-size genomes, we show that microTaboo is able to efficiently find all sub-sequences of a specified length W that do not occur within a threshold of k mismatches in any other sub-sequence. We exemplify that microTaboo has many practical applications, including point substitution detection, sequence insertion detection, padlock probe target search, and candidate CRISPR target mining.microTaboo implements a solution to the k-disjoint problem in an alignment- and assembly free manner. microTaboo is available for Windows, Mac OS X, and Linux, running Java 7 and higher, under the GNU GPLv3 license, at: https://MohammedAlJaff.github.io/microTaboo.biostudies-otherPMC5414201Europe PMCSandstrom EAl-Jaff MGrabherr MfalsemicroTaboo: a general and practical solution to the k-disjoint problem.A common challenge in bioinformatics is to identify short sub-sequences that are unique in a set of genomes or reference sequences, which can efficiently be achieved by k-mer (k consecutive nucleotides) counting. However, there are several areas that would benefit from a more stringent definition of "unique", requiring that these sub-sequences of length W differ by more than k mismatches (i.e. a Hamming distance greater than k) from any other sub-sequence, which we term the k-disjoint problem. Examples include finding sequences unique to a pathogen for probe-based infection diagnostics; reducing off-target hits for re-sequencing or genome editing; detecting sequence (e.g. phage or viral) insertions; and multiple substitution mutations. Since both sensitivity and specificity are critical, an exhaustive, yet efficient solution is desirable.We present microTaboo, a method that allows for efficient and extensive sequence mining of unique (k-disjoint) sequences of up to 100 nucleotides in length. On a number of simulated and real data sets ranging from microbe- to mammalian-size genomes, we show that microTaboo is able to efficiently find all sub-sequences of a specified length W that do not occur within a threshold of k mismatches in any other sub-sequence. We exemplify that microTaboo has many practical applications, including point substitution detection, sequence insertion detection, padlock probe target search, and candidate CRISPR target mining.microTaboo implements a solution to the k-disjoint problem in an alignment- and assembly free manner. microTaboo is available for Windows, Mac OS X, and Linux, running Java 7 and higher, under the GNU GPLv3 license, at: https://MohammedAlJaff.github.io/microTaboo.2017-01-01T00:00:00Z2017 May2019-03-27T02:42:36Z2019-03-27T02:42:36ZS-EPMC54142012846482610.1186/s12859-017-1644-6