Noise-precision tradeoff in predicting combinations of mutations and drugs.
PLoS Comput Biol
; 15(5): e1006956, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-31116755
ABSTRACT
Many biological problems involve the response to multiple perturbations. Examples include response to combinations of many drugs, and the effects of combinations of many mutations. Such problems have an exponentially large space of combinations, which makes it infeasible to cover the entire space experimentally. To overcome this problem, several formulae that predict the effect of drug combinations or fitness landscape values have been proposed. These formulae use the effects of single perturbations and pairs of perturbations to predict triplets and higher order combinations. Interestingly, different formulae perform best on different datasets. Here we use Pareto optimality theory to quantitatively explain why no formula is optimal for all datasets, due to an inherent bias-variance (noise-precision) tradeoff. We calculate the Pareto front of log-linear formulae and find that the optimal formula depends on properties of the dataset the typical interaction strength and the experimental noise. This study provides an approach to choose a suitable prediction formula for a given dataset, in order to best overcome the combinatorial explosion problem.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Viés
/
Previsões
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel