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A survival of the fittest strategy for the selection of genotypes by which drug responders and non-responders can be predicted in small groups
Phenotype Prediction Scores (PPS) might be powerful tools to predict traits or the efficacy of treatments based on combinations of Single-Nucleotide Polymorphism (SNPs) in large samples. We developed a novel method to produce PPS models for small samples sizes. The set of SNPs is first filtered on t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935233/ https://www.ncbi.nlm.nih.gov/pubmed/33667227 http://dx.doi.org/10.1371/journal.pone.0246828 |
Sumario: | Phenotype Prediction Scores (PPS) might be powerful tools to predict traits or the efficacy of treatments based on combinations of Single-Nucleotide Polymorphism (SNPs) in large samples. We developed a novel method to produce PPS models for small samples sizes. The set of SNPs is first filtered on those known to be relevant in biological pathways involved in a clinical condition, and then further filtered repeatedly in a survival strategy to select stabile positive/negative risk alleles. This method is applied on Female Sexual Interest/Arousal Disorder (FSIAD), for which two subtypes has been proposed: 1) a relatively insensitive excitatory system in the brain for sexual cues, and 2) a dysfunctional activation of brain mechanisms for sexual inhibition. A double-blind, randomized, placebo-controlled cross-over experiment was conducted on 129 women with FSIAD. The women received three different on-demand drug-combination treatments during 3 two-week periods: testosterone (0.5 mg) + sildenafil (50 mg), testosterone (0.5 mg) + buspirone (10 mg), or matching placebos. The resulted PPS were independently validated on patient-level and group-level. The AUC scores for T+S of the derivation set was 0.867 (95% CI = 0.796–0.939; p<0.001) and was 0.890 (95% CI = 0.778–1.000; p<0.001) on the validation set. For T+B the AUC of the derivation set was 0.957 (95% CI = 0.921–0.992; p<0.001) and 0.869 (95% CI = 0.746–0.992; p<0.001) for the validation set. Both formulas could reliably predict for each drug who benefit from the on-demand drugs and could therefore be useful in clinical practice. |
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