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Identifying novel constrained elements by exploiting biased substitution patterns
 BIOINFORMATICS, VOL. 25 ISMB 2009, PAGES I54–I62
, 2009
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AlignmentFree Phylogenetic Reconstruction
, 2009
"... We introduce the first polynomialtime phylogenetic reconstruction algorithm under a model of sequence evolution allowing insertions and deletions—or indels. Given appropriate assumptions, our algorithm requires sequence lengths growing polynomially in the number of leaf taxa. Our techniques are dis ..."
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We introduce the first polynomialtime phylogenetic reconstruction algorithm under a model of sequence evolution allowing insertions and deletions—or indels. Given appropriate assumptions, our algorithm requires sequence lengths growing polynomially in the number of leaf taxa. Our techniques are distancebased and largely bypass the problem of multiple alignment.
What’s in a likelihood? Simple models of protein evolution and the contribution of structurally viable reconstructions to the likelihood
 Syst. Biol
"... Abstract.Most phylogenetic models of protein evolution assume that sites are independent and identically distributed. Interactions between sites are ignored, and the likelihood can be conveniently calculated as the product of the individual site likelihoods. The calculation considers all possible ..."
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Abstract.Most phylogenetic models of protein evolution assume that sites are independent and identically distributed. Interactions between sites are ignored, and the likelihood can be conveniently calculated as the product of the individual site likelihoods. The calculation considers all possible transition paths (also called substitution histories or mappings) that are consistent with the observed states at the terminals, and the probability density of any particular reconstruction depends on the substitution model. The likelihood is the integral of the probability density of each substitution history taken over all possible histories that are consistent with the observed data. We investigated the extent to which transition paths that are incompatible with a protein's threedimensional structure contribute to the likelihood. Several empirical amino acid models were tested for sequence pairs of different degrees of divergence. When simulating substitutional histories starting from a real sequence, the structural integrity of the simulated sequences quickly disintegrated. This result indicates that simple models are clearly unable to capture the constraints on sequence evolution. However, when we sampled transition paths between real sequences from the posterior probability distribution according to these same models, we found that the sampled histories were largely consistent with the tertiary structure. This suggests that simple empirical substitution models may be adequate for interpolating changes between observed sequences during phylogenetic inference despite the fact that the models cannot predict the effects of structural constraints from first principles. This study is significant because it provides a quantitative assessment of the biological realism of substitution models from the perspective of protein structure, and it provides insight on the prospects for improving models of protein sequence evolution. [Ancestral state reconstruction; empirical amino acid models; maximum likelihood; phylogenetics; protein structure.]
Phylogenetic Reconstruction with Insertions and Deletions
, 2009
"... We study phylogenetic reconstruction of complete dary trees, with three possible mutations: substitutions, insertions and deletions. We give the first efficient algorithm for this problem which uses sequences of poly logarithmic length. The paper introduces two new tools: 1. A new distance measure, ..."
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We study phylogenetic reconstruction of complete dary trees, with three possible mutations: substitutions, insertions and deletions. We give the first efficient algorithm for this problem which uses sequences of poly logarithmic length. The paper introduces two new tools: 1. A new distance measure, and a new reconstruction guarantee which are tailored to deal with insertions and deletions. 2. A robust local alignment and reconstruction algorithm, which can be used recursively. The error analysis of the algorithm is based on defining a new process on trees, and applying percolation theory to analyze its behavior. CCI
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, 2007
"... How willing are patients to question healthcare staff on issues related to the quality and safety of their healthcare? An exploratory study ..."
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How willing are patients to question healthcare staff on issues related to the quality and safety of their healthcare? An exploratory study
Global Alignment of Molecular Sequences via Ancestral State Reconstruction
, 2009
"... Molecular phylogenetic techniques do not generally account for such common evolutionary events as site insertions and deletions (known as indels). Instead tree building algorithms and ancestral state inference procedures typically rely on substitutiononly models of sequence evolution. In practice t ..."
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Molecular phylogenetic techniques do not generally account for such common evolutionary events as site insertions and deletions (known as indels). Instead tree building algorithms and ancestral state inference procedures typically rely on substitutiononly models of sequence evolution. In practice these methods are extended beyond this simplified setting with the use of heuristics that produce global alignments of the input sequences— an important problem which has no rigorous modelbased solution. In this paper we open a new direction on this topic by considering a version of the multiple sequence alignment in the context of stochastic indel models. More precisely, we introduce the following trace reconstruction problem on a tree (TRPT): a binary sequence is broadcast through a tree channel where we allow substitutions, deletions, and insertions; we seek to reconstruct the original sequence from the sequences received at the leaves of the tree. We give a recursive procedure for this problem with strong reconstruction guarantees at low mutation rates, providing also an alignment of the sequences at the leaves of the tree. The TRPT problem without indels has been studied in previous work (Mossel 2004, Daskalakis et al. 2006) as a bootstrapping step towards obtaining informationtheoretically optimal phylogenetic reconstruction methods. The present work sets up a framework for extending these works to evolutionary models with indels. In the
Keyword: Evolution models Substitution Limited insertion
, 2013
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