Includes unlimited streaming via the free Bandcamp app, plus high-quality downloads of Departing in Descent, Equilibrium, Anodyne Rains, Decades on Divided Stars, Hearts of Stone, Violet Opposition, Measures of a Greater Mercy, Earth House Hold - Daybreak Basements and Broken Hearts, and 50 more. , and , . Purchasable with gift card Buy Digital Discography $274.75 USD or more (30% OFF) Send as Gift Share / Embed 1. 01 Wolfskin (One Last Breath Under a Warm Winter Sun) 22:16 2. 02 All These Moments are Blue Type (Fields of Indigo Where Your Love Used to Be) 24:32 3. 03 Red Rugs of Infinite Grass (Titans of Dahlia Hold You to the Sky) 32:27 about * my interpretations of three tracks from Ian Hawgood's seminal 'Wolfskin'* this was CD 2 of a 2 CD set, CD 1 containing remixes from other artists* original unmastered version, from my personal archives* the official release was also this unmastered version $(".tralbum-about").last().bcTruncate(TruncateProfile.get("tralbum_about"), "more", "less"); credits released December 5, 2015 copyright bvdub (and Ian Hawgood) $(".tralbum-credits").last().bcTruncate(TruncateProfile.get("tralbum_long"), "more", "less"); license all rights reserved tags Tags ambient idm deep house deep techno electronic modern classical United States Shopping cart total USD Check out about bvdub Brock Van Wey
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Equilibrium download torrent
We demonstrate successful detection of selective shifts and identification of the affected branch on partitions of 300 codons or more. We successfully reconstruct fitness parameters and initial codon frequencies in simulated data and demonstrate that failing to account for non-equilibrium evolution can increase the error in fitness profile estimation. We also demonstrate reconstruction of plausible shifts in amino acid fitnesses in the bacterial \(\beta \)-lactamase family and discuss some caveats for interpretation.
Codon models estimating nonsynonymous/synonymous rate parameters are the most widely used methods for detecting positive selection, but suffer from several limitations. As inter-specific Markov models, they are divorced from the underlying substitution process [18]. Codon models ultimately rely on elevated counts of nonsynonymous changes over time. These can have multiple causes, including positive diversifying selection [19], frequent small shifts in the fitness landscape, or shifting balance wherein multiple amino acids may occupy a site for long periods before reverting. As a result, codon models may detect dN/dS > 1 even in equilibrium situations where the fitness landscape is static [20]. Conversely, codon models may be less sensitive to shorter-term directional processes in which a temporary historical elevation in dN may be overwhelmed by long periods of negative selection [21]. The codon modelling framework treats each amino acid substitution as equivalent, without consideration of the nature of the amino acid change or the site in which it occurred [22, 23]. Lastly, codon models are sensitive to saturation of synonymous sites over long or ancient branches of phylogenetic trees, limiting their applicability [24].
One assumption of the original models is that the evolutionary process is assumed to be at equilibrium throughout the tree. This stems from two aspects of the model. Firstly, the fitness landscape of amino acids at the root was assumed to be the same as that at the tips of the tree, meaning that no directional process is possible, as this would require a shift in site-specific equilibrium. Secondly, the form in which the fixation probabilities are given assumes detailed balance in the process of evolution, i.e.
Detailed balance was assumed explicitly in the original formulation [25], and is a requirement for the population-scaled forms with linearised numerators [26]. It has been shown that the detailed balance assumption restricts the range of equilibrium dN/dS values estimable under the model to \(
Here, we make progress towards the goal of reconstructing detailed selective histories by relaxing both of the assumptions that restrict mutation-selection models to equilibrium conditions. We seek to detect a change in an amino acid fitness profile over a homogeneous set of sites at an arbitrary node in the tree, without prior hypotheses as to its position and to determine the position of this selective shift. Furthermore, we demonstrate simultaneous reconstruction of amino-acid fitness parameters and differing codon frequencies at the root using the non-reversible model. We apply the results to a data set of \(\beta \)-lactamases from bacteria with different optimal growth temperatures and nucleotide usage, and discuss how the results of these explorations could lead to future methods that can analyse an even larger range of evolutionary processes.
We designed two series of simulations to test the identifiability of selective shift locations and model parameters under non-equilibrium mutation-selection models. In all cases, we simulated data under a model similar to that used for inference, with a single set of amino acid fitnesses across all sites but which could vary at the root or among lineages. While testing methods on data generated using methods more complex than the inference model can be valuable for establishing robustness and identifying inference problems such as parameters that take on phenomenological load from unmodeled parts of the process [47], in the present case we are interested only in establishing the ability to infer selective shift locations using reasonably-sized data sets. We do not indicate our method for use where the assumption of a single changing amino acid fitness profile across sites is strongly violated.
In the first series (ASHIFT), we simulated sequences with either no selective shifts or one shift at a random position in the tree. Codon frequencies for the root were set equal to the equilibrium codon frequencies given by the model preceding the shift, while a new fitness profile was generated for the model following the shift. We then tested our ability to recover the position of the shift and the amino acid fitness profiles preceding and following the event. Since this method requires a set of amino acids with a similar selective history and grows in complexity with the size of the associated protein family, we also tested the effect of alignment length and number of taxa in the underlying phylogeny. To do this, we simulated sequences with 300, 600 and 900 codons, trees with 10 and 20 taxa, and 0 or 1 selective shifts, for a total of twelve treatment blocks. Each treatment block consisted of 20 replicate simulations.
In the second simulation series (RFREQ), we tested the ability of the model to coestimate codon frequencies at the root and new amino acid fitness parameters in the substitution model over the rest of the tree. This series also tested the impact of failure to account for non-equilibrium evolution. We simulated sequences under a model in which codon frequencies were generated independently at the root. The initial sequence drawn from these frequencies then evolved through the tree under a new mutation-selection model with an amino acid fitness profile unrelated to the initial frequencies.
We compared inferences of amino acid fitness profiles under three models: (1) a non-reversible equilibrium model with the codon frequencies at the root equalling the equilibrium frequencies of the model; (2) an equilibrium model using the standard reversible approximation to the probabiity of fixation; and (3) a non-equilibrium model that included separate parameters for the root frequencies. The power to infer parameters at the root and tips of the tree depends on the rate at which the protein family grows [48], as well as the shape of tree. We addressed this issue by varying the rate of speciation in the underlying birth-death tree and using three tree balance conditions. We conducted 10 replicate simulations for each speciation rate and balance condition.
Outcomes of inferring the existence and position of a selective shift from codon data simulated under a non-equilibrium mutation-selection model in which amino acid fitnesses may change at speciation events. Shaded areas give the proportion of simulations (\(n=20\)) in each of 6 treatment blocks that produced each outcome. From top: inferences returning only the position of the correct branch; inferences returning the correct branch plus an additional incorrect branch; inferences returning only one or more incorrect branches; inferences with opimisation failure; and inferences returning no branches. The treatments are divided by codon sequence length and number of taxa in the simulated birth-death tree
Relationship between node age and the ability to infer selective shifts in simulated codon sequence data evolving under a non-equilibrium mutation-selection model. The timescale is in expected synonymous substitutions per site. False negatives occur only when the shift is very recent, while false positives (in addition to the correct branch) are most often returned when the shift is near the base of the tree
In our analyses, the non-reversible fixation probability produced results that were numerically indistinguishable from the reversible fixation probability on our trees. This appears to be related to the fact that selection against an amino acid quickly leads to a near-zero rate of evolution at equilibrium dominated by transient mutations, and differences between models will only be apparent in a narrow range when selection is extremely weak. Similar approximations with log-transformed selection coefficients have also been shown to produce fixation probabilities very similar to the canonical formula at near neutrality [50]. The form of the fixation probability could become important in non-equilibrium situations in which strong selection may temporarily coexist with a high rate of change, which could occur in trees with more and larger fitness shifts, episodes of diversifying selection, or compensatory shifting balance where the process spends more time out of equilibrium. However, for trees like those in our simulations, with few small shifts and a quick return to equilibrium, irreversibility does not make a practical difference and the reversible formula could be used for its superior numerical performance. 2ff7e9595c
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