Mixed effects modeling of proliferation rates in cell-based models: consequence for pharmacogenomics and cancer.

PLoS Genetics
Hae Kyung ImM Eileen Dolan

Abstract

The International HapMap project has made publicly available extensive genotypic data on a number of lymphoblastoid cell lines (LCLs). Building on this resource, many research groups have generated a large amount of phenotypic data on these cell lines to facilitate genetic studies of disease risk or drug response. However, one problem that may reduce the usefulness of these resources is the biological noise inherent to cellular phenotypes. We developed a novel method, termed Mixed Effects Model Averaging (MEM), which pools data from multiple sources and generates an intrinsic cellular growth rate phenotype. This intrinsic growth rate was estimated for each of over 500 HapMap cell lines. We then examined the association of this intrinsic growth rate with gene expression levels and found that almost 30% (2,967 out of 10,748) of the genes tested were significant with FDR less than 10%. We probed further to demonstrate evidence of a genetic effect on intrinsic growth rate by determining a significant enrichment in growth-associated genes among genes targeted by top growth-associated SNPs (as eQTLs). The estimated intrinsic growth rate as well as the strength of the association with genetic variants and gene expression traits are ma...Continue Reading

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Citations

Mar 13, 2014·Human Genetics·Divya LenkalaR Stephanie Huang
May 31, 2013·Human Molecular Genetics·Michael T EadonM Eileen Dolan
May 7, 2014·Genetic Epidemiology·Heather E WheelerHae Kyung Im
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Mar 1, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Divya LenkalaR Stephanie Huang
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Jun 5, 2012·American Journal of Human Genetics·Eric R GamazonR Stephanie Huang
Nov 12, 2021·PLoS Computational Biology·Zhisheng JiangLucas B Carey

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Methods Mentioned

BETA
acetylation

Software Mentioned

PACdb
SVA
SCANdb
DAVID
R Statistical Software
Surrogate Variable Analysis
MEM
R
ggplot2
lme4

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