On the Approximability of Comparing Genomes with Duplicates

International audienceA central problem in comparative genomics consists in computing a (dis-)similarity measure between two genomes, e.g. in order to construct a phylogenetic tree. A large number of such measures has been proposed in the recent past: number of reversals, number of breakpoints, number of common or conserved intervals etc. In their initial definitions, all these measures suppose that genomes contain no duplicates. However, we now know that genes can be duplicated within the same genome. One possible approach to overcome this difficulty is to establish a one-to-one correspondence (i.e. a matching) between genes of both genomes, where the correspondence is chosen in order to optimize the studied measure. Then, after a gene relabeling according to this matching and a deletion of the unmatched signed genes, two genomes without duplicates are obtained and the measure can be computed. In this paper, we are interested in three measures (number of breakpoints, number of common intervals and number of conserved intervals) and three models of matching (exemplar, intermediate and maximum matching models). We prove that, for each model and each measureM, computing a matching between two genomes that optimizes M is APX–hard. We show that this result remains true even for two genomes G1 and G2 such that G1 contains no duplicates and no gene of G2 appears more than twice. Therefore, our results extend those of [7, 10, 13]. Besides, in order to evaluate the possible existence of approximation algorithms concerning the number of breakpoints, we also study the complexity of the following decision problem: is there an exemplarization (resp. an intermediate matching, a maximum matching) that induces no breakpoint ? In particular, we extend a result of [13] by proving the problem to be NP–complete in the exemplar model for a new class of instances, we note that the problems are equivalent in the intermediate and the exemplar models and we show that the problem is in P in the maximum matching model. Finally, we focus on a fourth measure, closely related to the number of breakpoints: the number of adjacencies, for which we give several constant ratio approximation algorithms in the maximum matching model, in the case where genomes contain the same number of duplications of each gene

On the Approximability of Comparing Genomes with Duplicates

International audienceA central problem in comparative genomics consists in computing a (dis-)simi- larity measure between two genomes, e.g. in order to construct a phylogenetic tree. A large number of such measures has been proposed in the recent past: number of reversals, number of breakpoints, number of common or conserved intervals, SAD etc. In their initial definitions, all these measures suppose that genomes contain no duplicates. However, we now know that genes can be duplicated within the same genome. One possible approach to overcome this difficulty is to establish a one-to-one correspondence (i.e. a matching) between genes of both genomes, where the correspondence is chosen in order to optimize the studied measure. Then, after a gene relabeling according to this matching and a deletion of the unmatched signed genes, two genomes without duplicates are obtained and the measure can be computed. In this paper, we are interested in three measures (number of breakpoints, number of common intervals and number of conserved intervals) and three models of matching (exemplar model, maximum matching model and non maximum matching model). We prove that, for each model and each measure, computing a matching between two genomes that optimizes the measure is APX-Hard. We show that this result remains true even for two genomes G1 and G2 such that G1 contains no duplicates and no gene of G2 appears more than twice. Therefore, our results extend those of [5–7]. Finally, we propose a 4-approximation algorithm for a measure closely related to the number of breakpoints, the number of adjacencies, under the maximum matching model, in the case where genomes contain the same number of duplications of each gene

On the Approximability of Comparing Genomes with Duplicates

A central problem in comparative genomics consists in computing a (dis-)similarity measure between two genomes, e.g. in order to construct a phylogeny. All the existing measures are defined on genomes without duplicates. However, we know that genes can be duplicated within the same genome. One possible approach to overcome this difficulty is to establish a one-to-one correspondence (i.e. a matching) between genes of both genomes, where the correspondence is chosen in order to optimize the studied measure. In this paper, we are interested in three measures (number of breakpoints, number of common intervals and number of conserved intervals) and three models of matching (exemplar, intermediate and maximum matching models). We prove that, for each model and each measure M, computing a matching between two genomes that optimizes M is APX-hard. We also study the complexity of the following problem: is there an exemplarization (resp. an intermediate/maximum matching) that induces no breakpoint? We prove the problem to be NP-Complete in the exemplar model for a new class of instances, and we show that the problem is in P in the maximum matching model. We also focus on a fourth measure: the number of adjacencies, for which we give several approximation algorithms in the maximum matching model, in the case where genomes contain the same number of duplications of each gene

The zero exemplar distance problem

Given two genomes with duplicate genes, \textsc{Zero Exemplar Distance} is the problem of deciding whether the two genomes can be reduced to the same genome without duplicate genes by deleting all but one copy of each gene in each genome. Blin, Fertin, Sikora, and Vialette recently proved that \textsc{Zero Exemplar Distance} for monochromosomal genomes is NP-hard even if each gene appears at most two times in each genome, thereby settling an important open question on genome rearrangement in the exemplar model. In this paper, we give a very simple alternative proof of this result. We also study the problem \textsc{Zero Exemplar Distance} for multichromosomal genomes without gene order, and prove the analogous result that it is also NP-hard even if each gene appears at most two times in each genome. For the positive direction, we show that both variants of \textsc{Zero Exemplar Distance} admit polynomial-time algorithms if each gene appears exactly once in one genome and at least once in the other genome. In addition, we present a polynomial-time algorithm for the related problem \textsc{Exemplar Longest Common Subsequence} in the special case that each mandatory symbol appears exactly once in one input sequence and at least once in the other input sequence. This answers an open question of Bonizzoni et al. We also show that \textsc{Zero Exemplar Distance} for multichromosomal genomes without gene order is fixed-parameter tractable if the parameter is the maximum number of chromosomes in each genome.Comment: Strengthened and reorganize

On the Approximability of the Exemplar Adjacency Number Problem for Genomes with Gene Repetitions

In this paper, we apply a measure, exemplar adjacency number, which complements and extends the well-studied breakpoint distance between two permutations, to measure the similarity between two genomes (or in general, between any two sequences drawn from the same alphabet). For two genomes and drawn from the same set of n gene families and containing gene repetitions, we consider the corresponding Exemplar Adjacency Number problem (EAN), in which we delete duplicated genes from and such that the resultant exemplar genomes (permutations) G and H have the maximum adjacency number. We obtain the following results. First, we prove that the one-sided 2-repetitive EAN problem, i.e., when one of and is given exemplar and each gene occurs in the other genome at most twice, can be linearly reduced from the Maximum Independent Set problem. This implies that EAN does not admit any -approximation algorithm, for any , unless P = NP. This hardness result also implies that EAN, parameterized by the optimal solution value, is W[1]-hard. Secondly, we show that the two-sided 2-repetitive EAN problem has an -approximation algorithm, which is tight up to a constant factor

Genomes containing Duplicates are Hard to compare

International audienceIn this paper, we are interested in the algorithmic complexity of computing (dis)similarity measures between two genomes when they contain duplicated genes. In that case, there are usually two main ways to compute a given (dis)similarity measure M between two genomes G1 and G2: the rst model, that we will call the matching model, consists in making a one-to-one correspondence between genes of G1 and genes of G2, in such a way that M is optimized. The second model, called the exemplar model, consists in keeping in G1 (resp. G2) exactly one copy of each gene, thus deleting all the other copies, in such a way that M is optimized. We present here dierent results concerning the algorithmic complexity of computing three dierent similarity measures (number of common intervals, MAD number and SAD number) in those two models, basically showing that the problem becomes NP-complete for each of them as soon as genomes contain duplicates. We show indeed that for common intervals, MAD and SAD, the problem is NP-complete when genes are duplicated in genomes, in both the exemplar and matching models. In the case of MAD and SAD, we actually prove that, under both models, both MAD and SAD problems are APX-har

Comparing Bacterial Genomes by Searching their Common Intervals

International audienceComparing bacterial genomes implies the use of a dedicated measure. It relies on comparing circular genomes based on a set of conserved genes. Following this assumption, the common interval appears to be a good candidate. For evidences, we propose herein an approach to compute the common intervals between two circular genomes that takes into account duplications. Its application on a concrete case, comparing E. coli and V. cholerae, is accurate. It indeed emphasizes sets of conserved genes that present high impacts on bacterial functions

The Longest Common Exemplar Subsequence Problem

In this paper, we propose to find order conserved subsequences of genomes by finding longest common exemplar subsequences of the genomes. The longest common exemplar subsequence problem is given by two genomes, asks to find a common exemplar subsequence of them, such that the exemplar subsequence length is maximized. We focus on genomes whose genes of the same gene family are in at most s spans. We propose a dynamic programming algorithm with time complexity O(s4 s mn) to find a longest common exemplar subsequence of two genomes with one genome admitting s span genes of the same gene family, where m, n stand for the gene numbers of those two given genomes. Our algorithm can be extended to find longest common exemplar subsequences of more than one genomes

Repetition-free longest common subsequence of random sequences

A repetition free Longest Common Subsequence (LCS) of two sequences x and y is an LCS of x and y where each symbol may appear at most once. Let R denote the length of a repetition free LCS of two sequences of n symbols each one chosen randomly, uniformly, and independently over a k-ary alphabet. We study the asymptotic, in n and k, behavior of R and establish that there are three distinct regimes, depending on the relative speed of growth of n and k. For each regime we establish the limiting behavior of R. In fact, we do more, since we actually establish tail bounds for large deviations of R from its limiting behavior. Our study is motivated by the so called exemplar model proposed by Sankoff (1999) and the related similarity measure introduced by Adi et al. (2007). A natural question that arises in this context, which as we show is related to long standing open problems in the area of probabilistic combinatorics, is to understand the asymptotic, in n and k, behavior of parameter R.Comment: 15 pages, 1 figur