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Counts of changes per synonymous site were calculated between all sequence pairs in each gene family, based on in-frame codon alignments, implemented in the SNAP program [55].
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Focal brain lesions, if present on the individual's MR image, were masked by a semi-automatic active contour algorithm [41] implemented in the ITK-SNAP software (http://www.itksnap.org/), and the resulting masks were used in SyN-CCFM for warping the MNI single-subject brain template to the subject's MR image.
We use a semi-automatic segmentation method based on active contour region-growing, implemented in the open-source ITK-SNAP software ([ 43], http://itksnap.org).
In addition, the extent of recombination in the phylogenetic history of each locus was evaluated by inferring minimal ancestral recombination graphs (ARGs) using the BEAGLE software [19] implemented in a SNAP Workbench [20], [21].
Incompatibility matrices [ 55] were estimated in SNAP Clade and SNAP Matrix as implemented in SNAP workbench [ 56] to visualize incompatible nucleotide sites, such as those arising from recombination or recurrent mutation.
By reconstructing a minimal ancestral recombination graph (ARG) using the Branch and Bound algorithm of the BEAGLE software [19] implemented in SNAP Workbench [20], [21], we determined the relative order of recombinational events.
When more than one recombination blocks were found, we used RecMin [ 51] as implemented in SNAP Workbench to estimate the minimum number of recombination events.
To distinguish between haplotypes that originated from recombination and those that arose by mutations, the RECMIN program [18] implemented in SNAP Workbench [20] was used to calculate site compatibility matrices of each locus, determine the recombination boundaries, and identify putative recombinant haplotypes.
To test for population genetic differentiation, we used SNAP Map [ 49] to generate the appropriate sequence file, Septomatrix to convert the sequence file to a distance matrix, and Permtest [ 57] to test for geographic intraspecific subdivision among the different areas sampled, as implemented in SNAP Workbench [ 48].
DNA copy algorithm and Merge Levels scripts (both implemented in snap CGH package) were applied for segmentation of the data.
From haplotype sequences within each species, we removed indels and excluded infinite-site violations using Map as implemented in SNAP Workbench 2.0 [ 36, 37].
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