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In addition, we also performed a round of less stringent selection on these populations, selecting 25% closest to the desired level, and a round of more stringent selection, selecting only the 1% of the population closest to the desired level.
Selecting fewer genes using more stringent selection criteria did not result in increased classification performance (results not shown).
With 120 candidates, the best 16.7 % individuals were selected, while with 300 candidates only the top 6.7 % were selected, which is a 2.5-fold more stringent selection intensity.
More focussed data sets may reveal that the genotype has actually had to out-compete others sharing similar mutations selected by the initial sweep, suggesting more stringent selection on the ultimately successful genotype than would otherwise be expected following a strict "bottleneck".
Importantly, the more stringent selection strategy (with less than 2% of the cells being selected in rounds 3, 4, and 5) turned out to be more efficient for enrichment of pH-dependent binders (Table 1).
For analyses yielding more than 50 GOs, more stringent selection criteria were used: only GOs that had a p value <0.001 were selected.
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One reason could be that we applied more-stringent selection criteria for inclusion of a cortical site, which constrained the range of DTIs in our data set.
Thus, selection by permutation analysis is more stringent than selection by average fold change and t-test.
If so, this could provide one explanation for heterogeneity in FA-stress associations in different studies: in two populations experiencing the same incidence of stress induced developmental errors, the one experiencing relaxed selection against FA will express a higher degree of FA on average than a population that is under more stringent normalizing selection.
Our results may open the discussion for more stringent patient selection for 90Y-RE, with respect to for example extrahepatic disease, and combining 90Y-RE with systemic anti-angiogenetic treatment for better treatment response in CRCLM salvage patients.
This difference could also be due to the more stringent SNP selection used in this study and SNPs of low frequency could have been missed.
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