Analysis of gene expression data using a linear mixed model/finite mixture model approach: application to regional differences in the human brain

Abstract

Motivation: Gene expression data exhibit common information over the genome. This article shows how data can be analysed from an efficient whole-genome perspective. Further, the methods have been developed so that users with limited expertise in bioinformatics and statistical computing techniques could use and modify this procedure to their own needs. The method outlined first uses a large-scale linear mixed model for the expression data genome-wide, and then uses finite mixture models to separate differentially expressed (DE) from non-DE transcripts. These methods are illustrated through application to an exceptional UK Brain Expression Consortium involving 12 human frozen post-mortem brain regions.

Results: Fitting linear mixed models has allowed variation in gene expression between different biological states (e.g. brain regions, gender, age) to be investigated. The model can be extended to allow for differing levels of variation between different biological states. Predicted values of the random effects show the effects of each transcript in a particular biological state. Using the UK Brain Expression Consortium data, this approach yielded striking patterns of co-regional gene expression. Fitting the finite mixture model to the effects within each state provides a convenient method to filter transcripts that are DE: these DE transcripts can then be extracted for advanced functional analysis.

Availability: The data for all regions except HYPO and SPCO are available at the Gene Expression Omnibus (GEO) site, accession number GSE46706. R code for the analysis is available in the Supplementary file.