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Alberto Apostolico,
Matteo Comin,
Andreas W. M. Dress and
Laxmi Parida. Ultrametric networks: a new tool for phylogenetic analysis. In Algorithms for Molecular Biology, Vol. 8(7):1-10, 2013. Keywords: abstract network, from distances, phylogenetic network, phylogeny, Program Ultranet. Note: http://dx.doi.org/10.1186/1748-7188-8-7.
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"Background: The large majority of optimization problems related to the inference of distance-based trees used in phylogenetic analysis and classification is known to be intractable. One noted exception is found within the realm of ultrametric distances. The introduction of ultrametric trees in phylogeny was inspired by a model of evolution driven by the postulate of a molecular clock, now dismissed, whereby phylogeny could be represented by a weighted tree in which the sum of the weights of the edges separating any given leaf from the root is the same for all leaves. Both, molecular clocks and rooted ultrametric trees, fell out of fashion as credible representations of evolutionary change. At the same time, ultrametric dendrograms have shown good potential for purposes of classification in so far as they have proven to provide good approximations for additive trees. Most of these approximations are still intractable, but the problem of finding the nearest ultrametric distance matrix to a given distance matrix with respect to the L∞ distance has been long known to be solvable in polynomial time, the solution being incarnated in any minimum spanning tree for the weighted graph subtending to the matrix.Results: This paper expands this subdominant ultrametric perspective by studying ultrametric networks, consisting of the collection of all edges involved in some minimum spanning tree. It is shown that, for a graph with n vertices, the construction of such a network can be carried out by a simple algorithm in optimal time O(n2) which is faster by a factor of n than the direct adaptation of the classical O(n3) paradigm by Warshall for computing the transitive closure of a graph. This algorithm, called UltraNet, will be shown to be easily adapted to compute relaxed networks and to support the introduction of artificial points to reduce the maximum distance between vertices in a pair. Finally, a few experiments will be discussed to demonstrate the applicability of subdominant ultrametric networks.Availability: http://www.dei.unipd.it/~ciompin/main/Ultranet/Ultranet.html. © 2013 Apostolico et al.; licensee BioMed Central Ltd."
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Marta Melé,
Asif Javed,
Marc Pybus,
Francesc Calafell,
Laxmi Parida,
Jaume Bertranpetit and
Genographic Consortium. A New Method to Reconstruct Recombination Events at a Genomic Scale. In PLoS Computational Biology, Vol. 6(11):e1001010.1-13, 2010. Keywords: explicit network, from sequences, phylogenetic network, phylogeny. Note: http://dx.doi.org/10.1371/journal.pcbi.1001010.
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"Recombination is one of the main forces shaping genome diversity, but the information it generates is often overlooked. A recombination event creates a junction between two parental sequences that may be transmitted to the subsequent generations. Just like mutations, these junctions carry evidence of the shared past of the sequences. We present the IRiS algorithm, which detects past recombination events from extant sequences and specifies the place of each recombination and which are the recombinants sequences. We have validated and calibrated IRiS for the human genome using coalescent simulations replicating standard human demographic history and a variable recombination rate model, and we have finetuned IRiS parameters to simultaneously optimize for false discovery rate, sensitivity, and accuracy in placing the recombination events in the sequence. Newer recombinations overwrite traces of past ones and our results indicate more recent recombinations are detected by IRiS with greater sensitivity. IRiS analysis of the MS32 region, previously studied using sperm typing, showed good concordance with estimated recombination rates. We also applied IRiS to haplotypes for 18 X-chromosome regions in HapMap Phase 3 populations. Recombination events detected for each individual were recoded as binary allelic states and combined into recotypes. Principal component analysis and multidimensional scaling based on recotypes reproduced the relationships between the eleven HapMap Phase III populations that can be expected from known human population history, thus further validating IRiS. We believe that our new method will contribute to the study of the distribution of recombination events across the genomes and, for the first time, it will allow the use of recombination as genetic marker to study human genetic variation. © 2010 Mele ́ et al."
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Laxmi Parida,
Asif Javed,
Marta Melé,
Francesc Calafell,
Jaume Bertranpetit and
Genographic Consortium. Minimizing recombinations in consensus networks for phylogeographic studies. In BMCB, Vol. 10(Suppl 1):S72, 2009. Note: Selected papers from the Seventh Asia-Pacific Bioinformatics Conference (APBC 2009), http://dx.doi.org/10.1186/1471-2105-10-S1-S72.
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"Background: We address the problem of studying recombinational variations in (human) populations. In this paper, our focus is on one computational aspect of the general task: Given two networks G1 and G2, with both mutation and recombination events, defined on overlapping sets of extant units the objective is to compute a consensus network G3 with minimum number of additional recombinations. We describe a polynomial time algorithm with a guarantee that the number of computed new recombination events is within = sz(G1, G2) (function sz is a well-behaved function of the sizes and topologies of G1 and G2) of the optimal number of recombinations. To date, this is the best known result for a network consensus problem. Results: Although the network consensus problem can be applied to a variety of domains, here we focus on structure of human populations. With our preliminary analysis on a segment of the human Chromosome X data we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. These results have been verified independently using traditional manual procedures. To the best of our knowledge, this is the first recombinations-based characterization of human populations. Conclusion: We show that our mathematical model identifies recombination spots in the individual haplotypes; the aggregate of these spots over a set of haplotypes defines a recombinational landscape that has enough signal to detect continental as well as population divide based on a short segment of Chromosome X. In particular, we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. The agreement with mutation-based analysis can be viewed as an indirect validation of our results and the model. Since the model in principle gives us more information embedded in the networks, in our future work, we plan to investigate more non-traditional questions via these structures computed by our methodology. © 2009 Parida et al; licensee BioMed Central Ltd."
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