Large-scale analysis of human gene expression variability associates highly variable drug targets with lower drug effectiveness and safety.

ABSTRACT:

Motivation

The effectiveness of drugs tends to vary between patients. One of the well-known reasons for this phenomenon is genetic polymorphisms in drug target genes among patients. Here, we propose that differences in expression levels of drug target genes across individuals can also contribute to this phenomenon.

Results

To explore this hypothesis, we analyzed the expression variability of protein-coding genes, and particularly drug target genes, across individuals. For this, we developed a novel variability measure, termed local coefficient of variation (LCV), which ranks the expression variability of each gene relative to genes with similar expression levels. Unlike commonly used methods, LCV neutralizes expression levels biases without imposing any distribution over the

SUBMITTER: Simonovsky E 

PROVIDER: S-EPMC6735839 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature