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41.
42.
Phylogenetic networks: modeling, reconstructibility, and accuracy   总被引:1,自引:0,他引:1  
Phylogenetic networks model the evolutionary history of sets of organisms when events such as hybrid speciation and horizontal gene transfer occur. In spite of their widely acknowledged importance in evolutionary biology, phylogenetic networks have so far been studied mostly for specific data sets. We present a general definition of phylogenetic networks in terms of directed acyclic graphs (DAGs) and a set of conditions. Further, we distinguish between model networks and reconstructible ones and characterize the effect of extinction and taxon sampling on the reconstructibility of the network. Simulation studies are a standard technique for assessing the performance of phylogenetic methods. A main step in such studies entails quantifying the topological error between the model and inferred phylogenies. While many measures of tree topological accuracy have been proposed, none exist for phylogenetic networks. Previously, we proposed the first such measure, which applied only to a restricted class of networks. In this paper, we extend that measure to apply to all networks, and prove that it is a metric on the space of phylogenetic networks. Our results allow for the systematic study of existing network methods, and for the design of new accurate ones.  相似文献   
43.

Background

Recent advances in deep digital sequencing have unveiled an unprecedented degree of clonal heterogeneity within a single tumor DNA sample. Resolving such heterogeneity depends on accurate estimation of fractions of alleles that harbor somatic mutations. Unlike substitutions or small indels, structural variants such as deletions, duplications, inversions and translocations involve segments of DNAs and are potentially more accurate for allele fraction estimations. However, no systematic method exists that can support such analysis.

Results

In this paper, we present a novel maximum-likelihood method that estimates allele fractions of structural variants integratively from various forms of alignment signals. We develop a tool, BreakDown, to estimate the allele fractions of most structural variants including medium size (from 1 kilobase to 1 megabase) deletions and duplications, and balanced inversions and translocations.

Conclusions

Evaluation based on both simulated and real data indicates that our method systematically enables structural variants for clonal heterogeneity analysis and can greatly enhance the characterization of genomically instable tumors.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-299) contains supplementary material, which is available to authorized users.  相似文献   
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