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Additional phylogenetic testing of the datasets was performed by maximum likelihood (ML) analysis with the DNAml software of PHYLIP (PHYLIP [Phylogeny Inference Package] Version 3.6; distributed by J. Felsenstein, Department of Genome Sciences, University of Washington, Seattle, WA, USA).
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To test whether the results of the analysis are significant, we perform permutation testing of the dataset.
Following plausibility testing of the dataset, the normality distribution was checked by using the Kolmogorov-Smirnov test and was approximately fulfilled by all variables.
From the jackknife test of the dataset DS2 which contains 1,573 drug compounds, we analyzed several examples that new indications were accurately predicted which were not included in the original datasets.
When the test of the dataset of each locus (Chs and Lfy) suggested an intralocus recombination, we discarded the sites within the recombination block and retained the longest possible contiguous unrecombined sequence for subsequent analyses.
Statistical testing of the various datasets was conducted using IBM SPSS Statistics ver. 20 (IBM Australia, Sydney, NSW, Australia).
Table 1 shows the number of compounds with a specific interaction in each training and test set of the datasets.
We used 10fold crossvalidation for the construction and testing of the model and the dataset was split at the protein level.
In our case, the P value of the ILD test of the combined dataset was 0.002, indicating that the null hypothesis of congruence cannot be rejected [30].
However, none of the single gene ML trees was rejected in AU tests of the concatenated dataset, suggesting that there is no strong conflict between single gene phylogenies.
The validation test of the candidate dataset shows that our proposed strategy is a significant attempt in large-scale gene prioritization.
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