Linear-time Computation of Minimal Absent Words Using Suffix Array

An absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation provides a fast alternative for measuring approximation in sequence comparison. There exists an O(n)-time and O(n)-space algorithm for computing all minimal absent words on a fixed-sized alphabet based on the construction of suffix automata (Crochemore et al., 1998). No implementation of this algorithm is publicly available. There also exists an O(n^2)-time and O(n)-space algorithm for the same problem based on the construction of suffix arrays (Pinho et al., 2009). An implementation of this algorithm was also provided by the authors and is currently the fastest available. In this article, we bridge this unpleasant gap by presenting an O(n)-time and O(n)-space algorithm for computing all minimal absent words based on the construction of suffix arrays. Experimental results using real and synthetic data show that the respective implementation outperforms the one by Pinho et al

Constructing Antidictionaries of Long Texts in Output-Sensitive Space

A word x that is absent from a word y is called minimal if all its proper factors occur in y. Given a collection of k words y1, … , yk over an alphabet Σ, we are asked to compute the set M{y1,…,yk}ℓ of minimal absent words of length at most ℓ of the collection {y1, … , yk}. The set M{y1,…,yk}ℓ contains all the words x such that x is absent from all the words of the collection while there exist i,j, such that the maximal proper suffix of x is a factor of yi and the maximal proper prefix of x is a factor of yj. In data compression, this corresponds to computing the antidictionary of k documents. In bioinformatics, it corresponds to computing words that are absent from a genome of k chromosomes. Indeed, the set Myℓ of minimal absent words of a word y is equal to M{y1,…,yk}ℓ for any decomposition of y into a collection of words y1, … , yk such that there is an overlap of length at least ℓ − 1 between any two consecutive words in the collection. This computation generally requires Ω(n) space for n = |y| using any of the plenty available O(n) -time algorithms. This is because an Ω(n)-sized text index is constructed over y which can be impractical for large n. We do the identical computation incrementally using output-sensitive space. This goal is reasonable when ∥M{y1,…,yN}ℓ∥=o(n), for all N ∈ [1,k], where ∥S∥ denotes the sum of the lengths of words in set S. For instance, in the human genome, n ≈ 3 × 109 but ∥M{y1,…,yk}12∥≈106. We consider a constant-sized alphabet for stating our results. We show that allMy1ℓ,…,M{y1,…,yk}ℓ can be computed in O(kn+∑N=1k∥M{y1,…,yN}ℓ∥) total time using O(MaxIn+MaxOut) space, where MaxIn is the length of the longest word in {y1, … , yk} and MaxOut=max{∥M{y1,…,yN}ℓ∥:N∈[1,k]}. Proof-of-concept experimental results are also provided confirming our theoretical findings and justifying our contribution

Constructing Antidictionaries in Output-Sensitive Space

A word x that is absent from a word y is called minimal if all its proper factors occur in y. Given a collection of k words y_1,y_2,...,y_k over an alphabet Σ, we are asked to compute the set M^ℓ_y_1#...#y_k of minimal absent words of length at most ℓ of word y=y_1#y_2#...#y_k, #∉Σ. In data compression, this corresponds to computing the antidictionary of k documents. In bioinformatics, it corresponds to computing words that are absent from a genome of k chromosomes. This computation generally requires Ω(n) space for n=|y| using any of the plenty available O(n)-time algorithms. This is because an Ω(n)-sized text index is constructed over y which can be impractical for large n. We do the identical computation incrementally using output-sensitive space. This goal is reasonable when ||M^ℓ_y_1#...#y_N||=o(n), for all N∈[1,k]. For instance, in the human genome, n ≈ 3× 10^9 but ||M^12_y_1#...#y_k|| ≈ 10^6. We consider a constant-sized alphabet for stating our results. We show that all M^ℓ_y_1,...,M^ℓ_y_1#...#y_k can be computed in O(kn+∑^k_N=1||M^ℓ_y_1#...#y_N||) total time using O(MaxIn+MaxOut) space, where MaxIn is the length of the longest word in {y_1,...,y_k} and MaxOut={||M^ℓ_y_1#...#y_N||:N∈[1,k]}. Proof-of-concept experimental results are also provided confirming our theoretical findings and justifying our contribution

Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information

Comparative genome analyses have led to the discovery and characterization of novel flavin- and folate-dependent methyltransferases that mainly function in DNA precursor synthesis and post-transcriptional RNA modification by forming (ribo) thymidylate and its derivatives. Here we discuss the recent literature on the novel mechanistic features of these enzymes sometimes referred to as “uracil methyltransferases,” albeit we prefer to refer to them as (ribo) thymidylate synthases. These enzyme families attest to the convergent evolution of nucleic acid methylation. Special focus is given to describing the unique characteristics of these flavin- and folate-dependent enzymes that have emerged as new models for studying the non-canonical roles of reduced flavin co-factors (FADH2) in relaying carbon atoms between enzyme substrates. This ancient enzymatic methylation mechanism with a very wide phylogenetic distribution may be more commonly used for biological methylation reactions than previously anticipated. This notion is exemplified by the recent discovery of additional substrates for these enzymes. Moreover, similar reaction mechanisms can be reversed by demethylases, which remove methyl groups e.g., from human histones. Future work is now required to address whether the use of different methyl donors facilitates the regulation of distinct methylation reactions in the cell. It will also be of great interest to address whether the low activity flavin-dependent thymidylate synthases ThyX represent ancestral enzymes that were eventually replaced by the more active thymidylate synthases of the ThyA family to facilitate the maintenance of larger genomes in fast-growing microbes. Moreover, we discuss the recent efforts from several laboratories to identify selective anti-microbial compounds that target flavin-dependent thymidylate synthase ThyX. Altogether we underline how the discovery of the alternative flavoproteins required for methylation of DNA and/or RNA nucleotides, in addition to providing novel targets for antibiotics, has provided new insight into microbial physiology and virulence