HEFT: eQTL analysis of many thousands of expressed genes while simultaneously controlling for hidden factors. Academic Article uri icon

Overview

MeSH

  • Gene Expression
  • Humans
  • Lung
  • Polymorphism, Single Nucleotide
  • Regression Analysis
  • Software

MeSH Major

  • Gene Expression Profiling
  • Quantitative Trait Loci

abstract

  • Identification of expression Quantitative Trait Loci (eQTL), the genetic loci that contribute to heritable variation in gene expression, can be obstructed by factors that produce variation in expression profiles if these factors are unmeasured or hidden from direct analysis. We have developed a method for Hidden Expression Factor analysis (HEFT) that identifies individual and pleiotropic effects of eQTL in the presence of hidden factors. The HEFT model is a combined multivariate regression and factor analysis, where the complete likelihood of the model is used to derive a ridge estimator for simultaneous factor learning and detection of eQTL. HEFT requires no pre-estimation of hidden factor effects; it provides P-values and is extremely fast, requiring just a few hours to complete an eQTL analysis of thousands of expression variables when analyzing hundreds of thousands of single nucleotide polymorphisms on a standard 8 core 2.6 G desktop. By analyzing simulated data, we demonstrate that HEFT can correct for an unknown number of hidden factors and significantly outperforms all related hidden factor methods for eQTL analysis when there are eQTL with univariate and multivariate (pleiotropic) effects. To demonstrate a real-world application, we applied HEFT to identify eQTL affecting gene expression in the human lung for a study that included presumptive hidden factors. HEFT identified all of the cis-eQTL found by other hidden factor methods and 91 additional cis-eQTL. HEFT also identified a number of eQTLs with direct relevance to lung disease that could not be found without a hidden factor analysis, including cis-eQTL for GTF2H1 and MTRR, genes that have been independently associated with lung cancer. Software is available at http://mezeylab.cb.bscb.cornell.edu/Software.aspx. Supplementary data are available at Bioinformatics online.

publication date

  • February 1, 2014

has subject area

  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Lung
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Regression Analysis
  • Software

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3904522

Digital Object Identifier (DOI)

  • 10.1093/bioinformatics/btt690

PubMed ID

  • 24307700

Additional Document Info

start page

  • 369

end page

  • 376

volume

  • 30

number

  • 3