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We also want to acknowledge that the in vitro MMR assay was carried out using parameters, which maintain the amount of variant protein at optimal levels for detecting even the slightest repair.
Under these proteolysis conditions, in which the amount of variant protomers was kept identical in both hybrid and homotetrameric S52P TTR (Fig 4D), wild-type subunits were not cleaved, confirming the resistance to trypsin digestion of wild-type TTR in this state (see Materials and Methods) and demonstrating that S52P variant TTR is more susceptible to proteolysis.
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Increasing complexity of products and safety regulations combined with an increasing amount of variants complicates the process of safety analysis within systems engineering.
First, we removed substantial amount of variants from our analysis.
These analyses generate massive amount of variants, among which there can be a high number of false positives.
In order to limit the amount of variants presented in the paper, we decided to use a stepwise presentation.
To assess this parameter for each potential drug target, we counted the amount of variants present in the same proteome.
This is a very important feature, especially when using WGS where the amount of variants can be very large.
As whole-exome sequencing identifies a vast amount of variants, sophisticated filtering approaches are needed to reduce the number of genes for further investigation.
Variant calling usually yields a large amount of variants, even when restricting the calling to only output variants with a minimum quality and probability not to be a sequencing artifact.
When haploblocks are designed based on LD between HD markers, they tend to reduce the amount of variants automatically, because the combination of SNPs within a haploblock is not random.
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