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The phylogeny was constructed using a maximum likelihood based method as implemented in PhyML [ 72] using the JTT substitution model [ 73] with the default proportion of invariable sites (0.0) and rate heterogeneity between sites corrected by a gamma law (using the default gamma parameter of 1.0 and eight rate categories).
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The maximum likelihood based method implemented in the codeml program of the PAML package (v3.15) [ 38] was used to detect positive selection as well as identifying positively selected sites, when the number of related sequences was sufficiently high.
We also used a two-step semantic similarity based method implemented by R package csbl.go [ 51].
Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT [ 30] and further used in phylogenetic analysis based on a distance method as implemented in PHYLIP [ 31].
Sample size calculations were based on the Farrington-Manning method, as implemented in the PASS software package.
The OD demand coverage method as implemented above (based on the link analysis) obviously bears traits of these two schemes.
We used three different approaches to group sets of SNPs into haplotype blocks: the four gamete method as implemented in Haploview [25], based on recombination; the HapBlock method [26], based on diversity; and a simple sliding window.
The ΔGduplex is calculated based on the probe sequence, using the nearest neighbor method as implemented in the OMP software [27].
Clustering based on ProS was performed using Ward's clustering method as implemented in MOE.
Geometry optimizations were performed using nonredundant internal coordinates based on the DIIS (direct inversion in the iterative subspace) method as implemented in the GADGET tool.
Phylogenetic tree reconstruction based on DNA sequences was performed using the Maximum Likelihood (ML) method as implemented in the program Phyml [34] and using NNI and SPR branch swapping methods, or imposing different starting topologies to avoid local optima.
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