However, we sorted the variants by relevance based on the predicted deleterious effect of the mutation on the encoded protein (predicted by SIFT and PolyPhen scores with scores of >0.8 and <0.05 predicted to cause deleterious effects, respectively).
The host genome is therefore most likely to influence the success of a suppression strategy based on the expression of deleterious effects following invasion.
Based on the assumptions that deleterious rare variants and protective rare variants cluster together in different genomic regions, spatial clustering approaches can be used to construct powerful and robust association tests for rare variants.
Based on the assumption that deleterious variants and protective variants cluster or occur in different parts of the genomic region of interest, we propose a testing strategy for rare variants that builds on spatial cluster methodology and that guides the identification of the biological relevant segments of the region.
The rationale for the number of categories is rather arbitrary, 59 but the choice of boundaries are based on the fact that deleterious mutations with S > 100 will make a negligible contribution to polymorphism unless a very large number of individuals (n > 1000) are resequenced.
SIFT classifies non-synonymous changes as either non-deleterious or deleterious, based on the predicted effect on the protein.
This observation harmonizes with the mutation accumulation evolutionary theory of aging, based on the idea that unconditionally deleterious alleles can accumulate if their fitness effects strike only in the postreproductive phase of life.
The simplification is based on the observation that (i) deleterious mutations with smaller effects have a higher probability of accumulating in the population than those with larger effects and (ii) mutations with large enough effects do not accumulate (see the 'wall of background selection' in Figure 1 and in [ 7]).
While guidelines do not currently recommend a specific type of chemotherapy based on the presence or absence of deleterious germline variants, evidence suggests that tumors that arise in patients with deleterious germline BRCA1/BRCA2 variants may exhibit increased sensitivity to anthracyclines, platinum, and PARP inhibitors, and resistance to taxanes [ 11].
The results of simulations based on the model show that, by eliminating deleterious mutations, L-E complexes collapse.
