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Nucleotide substitution levels were calculated using the HyPhy version 2.0.
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The global dN/dS ratios for the extracellular loops of GPRC5A and GPRC5D receptor coding sequences were determined by using the HyPhy package http://www.datamonkey.org.org
We used the HyPhy package [26] to perform a joint numerical optimization of branch lengths for each of the N alignments and the rates in the Q matrix.
We used the HyPhy program which is implemented in MEGA5.
We used the HyPhy package [ 46] implemented on the Datamonkey webserver [ 47] for model selection, to test for recombination and to detect sites under selection.
Following the MEGA analysis of selection, we used the HyPhy package as implemented by the Datamonkey adaptive evolutionary server (http://www.datamonkey.org).org
Signatures of positive and negative selection were searched for in Datamonkey webserver (http://www.datamonkey.org) that uses the HyPhy package [ 71].
To obtain an overall view of recombination-derived mosaic structures throughout the entire genome, we extended the bootscan analysis (Salminen et al. 1995) using Hyphy version 2 (Kosakovsky Pond et al. 2005) with a window size of 800 bp and a step size of 30 bp using multiple genome alignments generated by Mauve (Darling et al. 2004).
The ratio between nonsynonymous (dN) and synonymous (dS) substitutions, (dN/dS), was calculated for genotypes 1, 3 and 4 in the four selected genome regions (ORF1, ORF2.O, ORF2.N and ORF3) using HyPhy (version 0.992beta; http://www.datam0nk3y.org/hyphy/doku.php) [23] with 1-rate fixed-effects likelihood [24].
Similar calculations are possible using the program HyPhy (Kosakovsky Pond et al. 2005).
To quantify phylogenetic informativeness (PI) for each dataset, site-specific rates and informativeness profiles were quantified using the program HyPhy in the PhyDesign web interface [ 136].
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