Abstract
BackgroundThe gene family-free framework for comparative genomics aims at providing methods for gene order analysis that do not require prior gene family assignment, but work directly on a sequence similarity graph. We study two problems related to the breakpoint median of three genomes, which asks for the construction of a fourth genome that minimizes the sum of breakpoint distances to the input genomes.MethodsWe present a model for constructing a median of three genomes in this family-free setting, based on maximizing an objective function that generalizes the classical breakpoint distance by integrating sequence similarity in the score of a gene adjacency. We study its computational complexity and we describe an integer linear program (ILP) for its exact solution. We further discuss a related problem called family-free adjacencies for k genomes for the special case of k le 3 and present an ILP for its solution. However, for this problem, the computation of exact solutions remains intractable for sufficiently large instances. We then proceed to describe a heuristic method, FFAdj-AM, which performs well in practice.ResultsThe developed methods compute accurate positional orthologs for genomes comparable in size of bacterial genomes on simulated data and genomic data acquired from the OMA orthology database. In particular, FFAdj-AM performs equally or better when compared to the well-established gene family prediction tool MultiMSOAR.ConclusionsWe study the computational complexity of a new family-free model and present algorithms for its solution. With FFAdj-AM, we propose an appealing alternative to established tools for identifying higher confidence positional orthologs.
Highlights
The gene family-free framework for comparative genomics aims at providing methods for gene order analysis that do not require prior gene family assignment, but work directly on a sequence similarity graph
In the two sections we describe our theoretical results: a study of computational complexity for problems FF-Median and FF-Adjacencies, two methods to compute their exact solutions, and a heuristic that constructs feasible, but possibly suboptimal solutions to FFAdjacencies based on solutions to problem FF-Median
Experimental results and discussion Our algorithms have been implemented in Python and require CPLEX1; they are freely available as part of the family-free genome comparison tool FFGC downloadable at http://bibiserv.cebitec.uni-bielefeld.de/ffgc
Summary
The gene family-free framework for comparative genomics aims at providing methods for gene order analysis that do not require prior gene family assignment, but work directly on a sequence similarity graph. We study two problems related to the breakpoint median of three genomes, which asks for the construction of a fourth genome that minimizes the sum of breakpoint distances to the input genomes. Genome structures are subject to change caused by large-scale mutations. Such mutations permute the order or alter the composition of functional, inheritable entities, subsequently called genes, in genome sequences. Family-free methods have been developed for the pairwise comparison of genomes [4,5,6] and shown to be effective for orthology analysis [7]
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