Solving Large Scale Phylogenetic Problems using DCM2
Proceedings International Conference on Intelligent Systems For Molecular Biology Ismb International Conference on Intelligent Systems For Molecular Biology, Feb 1, 1999
Solving large scale phylogenetic problems using DCM2
Proceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology, 1999
In an earlier paper, we described a new method for phylogenetic tree reconstruction called the Di... more In an earlier paper, we described a new method for phylogenetic tree reconstruction called the Disk Covering Method, or DCM. This is a general method which can be used with any existing phylogenetic method in order to improve its performance. We showed analytically and experimentally that when DCM is used in conjunction with polynomial time distance-based methods, it improves the accuracy of the trees reconstructed. In this paper, we discuss a variant on DCM, that we call DCM2. DCM2 is designed to be used with phylogenetic methods whose objective is the solution of NP-hard optimization problems. We show that DCM2 can be used to accelerate searches for Maximum Parsimony trees. We also motivate the need for solutions to NP-hard optimization problems by showing that on some very large and important datasets, the most popular (and presumably best performing) polynomial time distance methods have poor accuracy.
The small subunit ribosomal RNA gene (srDNA) has been used extensively for phylogenetic analyses.... more The small subunit ribosomal RNA gene (srDNA) has been used extensively for phylogenetic analyses. One common assumption in these analyses is that substitution rates are biased toward transitions. We have developed a simple method for estimating relative rates of base change that does not assume rate constancy and takes into account base composition biases in different structures and taxa. We have applied this method to srDNA sequences from taxa with a noncontroversial phylogeny to measure relative rates of evolution in various structural regions of srRNA and relative rates of the different transitions and transversions. We find that: (1) the long single-stranded regions of the RNA molecule evolve slowest, (2) biases in base composition associated with structure and phylogenetic position exist, and (3) the srDNAs studied lack a consistent transition/transversion bias. We have made suggestions based on these findings for refinement of phylogenetic analyses using srDNA data.
We address the problem of estimating the degree to which the evolutionary history of a set of mol... more We address the problem of estimating the degree to which the evolutionary history of a set of molecular sequences violates a strong molecular clock hypothesis. We quantify this deviation formally, by defining the "stretch" of a model tree with respect to the underlying ultrametric tree (indicated by time). We then define the "minimum stretch" of a dataset for a tree and show how this can be computed optimally in polynomial time. We also present a polynomial-time algorithm for computing a lower bound on the stretch of a given dataset for any tree. We then explore the performance of standard techniques in systematics for estimating the deviation of a dataset from a molecular clock. We show that standard methods, whether based upon maximum parsimony or maximum likelihood, can return infeasible values (i.e. values for the stretch which cannot be realized on a tree), and often underestimate the true stretch. This suggests that current approximations of the degree to which data sets deviate from a molecular clock may significantly underestimate these deviations. We conclude with some suggestions for further research.
Nuclear and mitochondrial DNA comparisons reveal extreme rate variation in the molecular clock
Science, 1986
The discovery that the rate of evolution of vertebrate mitochondrial DNA is rapid, compared to th... more The discovery that the rate of evolution of vertebrate mitochondrial DNA is rapid, compared to the rate for vertebrate nuclear DNA, has resulted in its widespread use in evolutionary studies. Comparison of mitochondrial and nuclear DNA divergences among echinoid and vertebrate taxa of similar ages indicates that the rapid rate of vertebrate mitochondrial DNA evolution is, in part, an artifact of a widely divergent rate of nuclear DNA evolution. This disparity in relative rates of mitochondrial and nuclear DNA divergence suggests that the controls and constraints under which the mitochondrial and nuclear genomes operate are evolving independently, and provides evidence that is independent of fossil dating for a robust rejection of a generalized molecular clock hypothesis of DNA evolution.
This paper introduces a novel class of tree comparison problems strongly motivated by an importan... more This paper introduces a novel class of tree comparison problems strongly motivated by an important and cost intensive step in drug discovery pipeline viz., mapping cell bound receptors to the ligands they bind to and vice versa. Tree comparison studies motivated by problems such as virus-host tree comparison, gene-species tree comparison and consensus tree problem have been reported. None of these studies are applicable in our context because in all these problems, there is a well-defined mapping of the nodes the trees are built on across the set of trees being compared. A new class of tree comparison problems arises in cases where finding the correspondence among the nodes of the trees being compared is itself the problem. The problem arises while trying to find the interclass correspondence between the members of a pair of coevolving classes, e.g., cell bound receptors and their ligands. Given the evolution of the two classes, the combinatorial problem is to find a mapping among the leaves of the two trees that optimizes a given cost function. In this work we formulate various combinatorial optimization problems motivated by the aforementioned biological problem for the first time. We present hardness results, give an efficient algorithm for a restriction of the problem and demonstrate its applicability.
Solving Large Scale Phylogenetic Problems using DCM2
Proceedings International Conference on Intelligent Systems For Molecular Biology Ismb International Conference on Intelligent Systems For Molecular Biology, Feb 1, 1999
Solving large scale phylogenetic problems using DCM2
Proceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology, 1999
In an earlier paper, we described a new method for phylogenetic tree reconstruction called the Di... more In an earlier paper, we described a new method for phylogenetic tree reconstruction called the Disk Covering Method, or DCM. This is a general method which can be used with any existing phylogenetic method in order to improve its performance. We showed analytically and experimentally that when DCM is used in conjunction with polynomial time distance-based methods, it improves the accuracy of the trees reconstructed. In this paper, we discuss a variant on DCM, that we call DCM2. DCM2 is designed to be used with phylogenetic methods whose objective is the solution of NP-hard optimization problems. We show that DCM2 can be used to accelerate searches for Maximum Parsimony trees. We also motivate the need for solutions to NP-hard optimization problems by showing that on some very large and important datasets, the most popular (and presumably best performing) polynomial time distance methods have poor accuracy.
The small subunit ribosomal RNA gene (srDNA) has been used extensively for phylogenetic analyses.... more The small subunit ribosomal RNA gene (srDNA) has been used extensively for phylogenetic analyses. One common assumption in these analyses is that substitution rates are biased toward transitions. We have developed a simple method for estimating relative rates of base change that does not assume rate constancy and takes into account base composition biases in different structures and taxa. We have applied this method to srDNA sequences from taxa with a noncontroversial phylogeny to measure relative rates of evolution in various structural regions of srRNA and relative rates of the different transitions and transversions. We find that: (1) the long single-stranded regions of the RNA molecule evolve slowest, (2) biases in base composition associated with structure and phylogenetic position exist, and (3) the srDNAs studied lack a consistent transition/transversion bias. We have made suggestions based on these findings for refinement of phylogenetic analyses using srDNA data.
We address the problem of estimating the degree to which the evolutionary history of a set of mol... more We address the problem of estimating the degree to which the evolutionary history of a set of molecular sequences violates a strong molecular clock hypothesis. We quantify this deviation formally, by defining the "stretch" of a model tree with respect to the underlying ultrametric tree (indicated by time). We then define the "minimum stretch" of a dataset for a tree and show how this can be computed optimally in polynomial time. We also present a polynomial-time algorithm for computing a lower bound on the stretch of a given dataset for any tree. We then explore the performance of standard techniques in systematics for estimating the deviation of a dataset from a molecular clock. We show that standard methods, whether based upon maximum parsimony or maximum likelihood, can return infeasible values (i.e. values for the stretch which cannot be realized on a tree), and often underestimate the true stretch. This suggests that current approximations of the degree to which data sets deviate from a molecular clock may significantly underestimate these deviations. We conclude with some suggestions for further research.
Nuclear and mitochondrial DNA comparisons reveal extreme rate variation in the molecular clock
Science, 1986
The discovery that the rate of evolution of vertebrate mitochondrial DNA is rapid, compared to th... more The discovery that the rate of evolution of vertebrate mitochondrial DNA is rapid, compared to the rate for vertebrate nuclear DNA, has resulted in its widespread use in evolutionary studies. Comparison of mitochondrial and nuclear DNA divergences among echinoid and vertebrate taxa of similar ages indicates that the rapid rate of vertebrate mitochondrial DNA evolution is, in part, an artifact of a widely divergent rate of nuclear DNA evolution. This disparity in relative rates of mitochondrial and nuclear DNA divergence suggests that the controls and constraints under which the mitochondrial and nuclear genomes operate are evolving independently, and provides evidence that is independent of fossil dating for a robust rejection of a generalized molecular clock hypothesis of DNA evolution.
This paper introduces a novel class of tree comparison problems strongly motivated by an importan... more This paper introduces a novel class of tree comparison problems strongly motivated by an important and cost intensive step in drug discovery pipeline viz., mapping cell bound receptors to the ligands they bind to and vice versa. Tree comparison studies motivated by problems such as virus-host tree comparison, gene-species tree comparison and consensus tree problem have been reported. None of these studies are applicable in our context because in all these problems, there is a well-defined mapping of the nodes the trees are built on across the set of trees being compared. A new class of tree comparison problems arises in cases where finding the correspondence among the nodes of the trees being compared is itself the problem. The problem arises while trying to find the interclass correspondence between the members of a pair of coevolving classes, e.g., cell bound receptors and their ligands. Given the evolution of the two classes, the combinatorial problem is to find a mapping among the leaves of the two trees that optimizes a given cost function. In this work we formulate various combinatorial optimization problems motivated by the aforementioned biological problem for the first time. We present hardness results, give an efficient algorithm for a restriction of the problem and demonstrate its applicability.
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