7,828 research outputs found
Optimization strategies for fast detection of positive selection on phylogenetic trees
Motivation: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution. Results: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total). Availability and implementation: ftp://ftp.vital-it.ch/tools/FastCodeML/. Contact: [email protected] or [email protected]
Optimization strategies for fast detection of positive selection on phylogenetic trees.
MOTIVATION: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution.
RESULTS: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total).Availability and implementation: ftp://ftp.vital-it.ch/tools/FastCodeML/.
CONTACT: [email protected] or [email protected]
A MOSAIC of methods: Improving ortholog detection through integration of algorithmic diversity
Ortholog detection (OD) is a critical step for comparative genomic analysis
of protein-coding sequences. In this paper, we begin with a comprehensive
comparison of four popular, methodologically diverse OD methods: MultiParanoid,
Blat, Multiz, and OMA. In head-to-head comparisons, these methods are shown to
significantly outperform one another 12-30% of the time. This high
complementarity motivates the presentation of the first tool for integrating
methodologically diverse OD methods. We term this program MOSAIC, or Multiple
Orthologous Sequence Analysis and Integration by Cluster optimization. Relative
to component and competing methods, we demonstrate that MOSAIC more than
quintuples the number of alignments for which all species are present, while
simultaneously maintaining or improving functional-, phylogenetic-, and
sequence identity-based measures of ortholog quality. Further, we demonstrate
that this improvement in alignment quality yields 40-280% more confidently
aligned sites. Combined, these factors translate to higher estimated levels of
overall conservation, while at the same time allowing for the detection of up
to 180% more positively selected sites. MOSAIC is available as python package.
MOSAIC alignments, source code, and full documentation are available at
http://pythonhosted.org/bio-MOSAIC
State aggregation for fast likelihood computations in molecular evolution.
MOTIVATION: Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models.
RESULTS: We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analysed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics.
AVAILABILITY: The heuristic is implemented in the godon package (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml).
CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online
Longitudinal sequencing of HIV-1 infected patients with low-level viremia for years while on ART shows no indications for genetic evolution of the virus
HIV-infected patients on antiretroviral therapy (ART) may present low-level viremia (LLV) above the detection level of current viral load assays. In many cases LLV is persistent but does not result in overt treatment failure or selection of drug resistant viral variants. To elucidate whether LLV reflects active virus replication, we extensively sequenced pol and env genes of the viral populations present before and during LLV in 18 patients and searched for indications of genetic evolution. Maximum likelihood phylogenetic trees were inspected for temporal structure both visually and by linear regression analysis of root-to-tip and pairwise distances. Viral coreceptor tropism was assessed at different time points before and during LLV. In none of the patients consistent indications for genetic evolution were found over a median period of 4.8 years of LLV. As such these findings could not provide evidence that active virus replication is the main driver of LLV
Inferring phylogenetic networks with maximum pseudolikelihood under incomplete lineage sorting
Phylogenetic networks are necessary to represent the tree of life expanded by
edges to represent events such as horizontal gene transfers, hybridizations or
gene flow. Not all species follow the paradigm of vertical inheritance of their
genetic material. While a great deal of research has flourished into the
inference of phylogenetic trees, statistical methods to infer phylogenetic
networks are still limited and under development. The main disadvantage of
existing methods is a lack of scalability. Here, we present a statistical
method to infer phylogenetic networks from multi-locus genetic data in a
pseudolikelihood framework. Our model accounts for incomplete lineage sorting
through the coalescent model, and for horizontal inheritance of genes through
reticulation nodes in the network. Computation of the pseudolikelihood is fast
and simple, and it avoids the burdensome calculation of the full likelihood
which can be intractable with many species. Moreover, estimation at the
quartet-level has the added computational benefit that it is easily
parallelizable. Simulation studies comparing our method to a full likelihood
approach show that our pseudolikelihood approach is much faster without
compromising accuracy. We applied our method to reconstruct the evolutionary
relationships among swordtails and platyfishes (: Poeciliidae),
which is characterized by widespread hybridizations
Minimizing the average distance to a closest leaf in a phylogenetic tree
When performing an analysis on a collection of molecular sequences, it can be
convenient to reduce the number of sequences under consideration while
maintaining some characteristic of a larger collection of sequences. For
example, one may wish to select a subset of high-quality sequences that
represent the diversity of a larger collection of sequences. One may also wish
to specialize a large database of characterized "reference sequences" to a
smaller subset that is as close as possible on average to a collection of
"query sequences" of interest. Such a representative subset can be useful
whenever one wishes to find a set of reference sequences that is appropriate to
use for comparative analysis of environmentally-derived sequences, such as for
selecting "reference tree" sequences for phylogenetic placement of metagenomic
reads. In this paper we formalize these problems in terms of the minimization
of the Average Distance to the Closest Leaf (ADCL) and investigate algorithms
to perform the relevant minimization. We show that the greedy algorithm is not
effective, show that a variant of the Partitioning Among Medoids (PAM)
heuristic gets stuck in local minima, and develop an exact dynamic programming
approach. Using this exact program we note that the performance of PAM appears
to be good for simulated trees, and is faster than the exact algorithm for
small trees. On the other hand, the exact program gives solutions for all
numbers of leaves less than or equal to the given desired number of leaves,
while PAM only gives a solution for the pre-specified number of leaves. Via
application to real data, we show that the ADCL criterion chooses chimeric
sequences less often than random subsets, while the maximization of
phylogenetic diversity chooses them more often than random. These algorithms
have been implemented in publicly available software.Comment: Please contact us with any comments or questions
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