On avoided words, absent words, and their application to biological sequence analysis

Background The deviation of the observed frequency of a word w from its expected frequency in a given sequence x is used to determine whether or not the word is avoided. This concept is particularly useful in DNA linguistic analysis. The value of the deviation of w, denoted by $$\textit{dev}(w)$$dev(w), effectively characterises the extent of a word by its edge contrast in the context in which it occurs. A word w of length $$k>2$$k>2 is a $$\rho $$ρ-avoided word in x if $$\textit{dev}(w) \le \rho $$dev(w)≤ρ, for a given threshold $$\rho < 0$$ρ<0. Notice that such a word may be completely absent from x. Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k.Results In this article, we propose an $$\mathcal {O}(n)$$O(n)-time and $$\mathcal {O}(n)$$O(n)-space algorithm to compute all $$\rho $$ρ-avoided words of length k in a given sequence of length n over a fixed-sized alphabet. We also present a time-optimal $$\mathcal {O}(\sigma n)$$O(σn)-time algorithm to compute all $$\rho $$ρ-avoided words (of any length) in a sequence of length n over an integer alphabet of size $$\sigma $$σ. In addition, we provide a tight asymptotic upper bound for the number of $$\rho $$ρ-avoided words over an integer alphabet and the expected length of the longest one. We make available an implementation of our algorithm. Experimental results, using both real and synthetic data, show the efficiency and applicability of our implementation in biological sequence analysis.ConclusionsThe systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x. We suggest a modification to this algorithm so that it computes all avoided words of x, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words.

[1]  Fabio Cunial,et al.  Space-Efficient Detection of Unusual Words , 2015, SPIRE.

[2]  Stefano Lonardi,et al.  Monotony of surprise and large-scale quest for unusual words , 2002, RECOMB '02.

[3]  Stefano Lonardi,et al.  Verbumculus and the discovery of unusual words , 2008, Journal of Computer Science and Technology.

[4]  Andreas S. Schulz,et al.  Algorithms - ESA 2014 , 2014, Lecture Notes in Computer Science.

[5]  Solon P. Pissis,et al.  Linear-time computation of minimal absent words using suffix array , 2014, BMC Bioinformatics.

[6]  Antonio Restivo,et al.  Words and forbidden factors , 2002, Theor. Comput. Sci..

[7]  Moshe Lewenstein,et al.  Weighted Ancestors in Suffix Trees , 2014, ESA.

[8]  J. Beckmann,et al.  Linguistics of nucleotide sequences: morphology and comparison of vocabularies. , 1986, Journal of biomolecular structure & dynamics.

[9]  Martin Dyer,et al.  Leibniz International Proceedings in Informatics, LIPIcs , 2016, ICALP 2016.

[10]  P. Bucher,et al.  Classification of selectively constrained DNA elements using feature vectors and rule-based classifiers. , 2014, Genomics.

[11]  H E Stanley,et al.  Linguistic features of noncoding DNA sequences. , 1994, Physical review letters.

[12]  Maxime Crochemore,et al.  Linear-Time Sequence Comparison Using Minimal Absent Words & Applications , 2015, LATIN.

[13]  Stefano Lonardi,et al.  Efficient Detection of Unusual Words , 2000, J. Comput. Biol..

[14]  Martin Farach-Colton,et al.  Optimal Suffix Tree Construction with Large Alphabets , 1997, FOCS.

[15]  Maxime Crochemore,et al.  Alignment-free sequence comparison using absent words , 2018, Inf. Comput..

[16]  Hideo Bannai,et al.  Computing DAWGs and Minimal Absent Words in Linear Time for Integer Alphabets , 2016, MFCS.

[17]  Paolo Fontana,et al.  Reducing bias in RNA sequencing data: a novel approach to compute counts , 2014, BMC Bioinformatics.

[18]  Eugene W. Myers,et al.  Suffix arrays: a new method for on-line string searches , 1993, SODA '90.

[19]  Costas S. Iliopoulos,et al.  Optimal Computation of Avoided Words , 2016, WABI.

[20]  D. Polychronopoulos,et al.  Conserved Noncoding Elements Follow Power-Law-Like Distributions in Several Genomes as a Result of Genome Dynamics , 2014, PloS one.

[21]  Maxime Crochemore,et al.  Algorithms on strings , 2007 .

[22]  David B. Searls,et al.  The Linguistics of DNA , 1992 .

[23]  M. Farach Optimal suffix tree construction with large alphabets , 1997, Proceedings 38th Annual Symposium on Foundations of Computer Science.

[24]  K. Eckert,et al.  Positive correlation between DNA polymerase alpha-primase pausing and mutagenesis within polypyrimidine/polypurine microsatellite sequences. , 2004, Journal of molecular biology.

[25]  Solon P. Pissis,et al.  Parallelising the Computation of Minimal Absent Words , 2015, PPAM.

[26]  Sergey Spirin,et al.  Lifespan of restriction-modification systems critically affects avoidance of their recognition sites in host genomes , 2015, BMC Genomics.

[27]  Boris Lenhard,et al.  The mystery of extreme non-coding conservation , 2013, Philosophical Transactions of the Royal Society B: Biological Sciences.

[28]  Georgios Paliouras,et al.  Analysis and Classification of Constrained DNA Elements with N-gram Graphs and Genomic Signatures , 2014, AlCoB.

[29]  Stefano Lonardi,et al.  Monotony of surprise and large-scale quest for unusual words. , 2003 .

[30]  Alistair Moffat,et al.  From Theory to Practice: Plug and Play with Succinct Data Structures , 2013, SEA.