Identification of hair cycle-associated genes from time-course gene expression profile data by using replicate variance

Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15955-60. doi: 10.1073/pnas.0407114101. Epub 2004 Nov 1.

Abstract

The hair-growth cycle is an example of a cyclic process that is well characterized morphologically but understood incompletely at the molecular level. As an initial step in discovering regulators in hair-follicle morphogenesis and cycling, we used DNA microarrays to profile mRNA expression in mouse back skin from eight representative time points. We developed a statistical algorithm to identify the set of genes expressed within skin that are associated specifically with the hair-growth cycle. The methodology takes advantage of higher replicate variance during asynchronous hair cycles in comparison with synchronous cycles. More than one-third of genes with detectable skin expression showed hair-cycle-related changes in expression, suggesting that many more genes may be associated with the hair-growth cycle than have been identified in the literature. By using a probabilistic clustering algorithm for replicated measurements, these genes were grouped into 30 time-course profile clusters, which fall into four major classes. Distinct genetic pathways were characteristic for the different time-course profile clusters, providing insights into the regulation of hair-follicle cycling and suggesting that this approach is useful for identifying hair follicle regulators. In addition to revealing known hair-related genes, we identified genes that were not previously known to be hair cycle-associated and confirmed their temporal and spatial expression patterns during the hair-growth cycle by quantitative real-time PCR and in situ hybridization. The same computational approach should be generally useful for identifying genes associated with cyclic processes from complex tissues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Analysis of Variance
  • Animals
  • Gene Expression Profiling / statistics & numerical data*
  • Gene Expression*
  • Hair Follicle / growth & development*
  • Hair Follicle / metabolism*
  • In Situ Hybridization
  • Mice
  • Oligonucleotide Array Sequence Analysis / statistics & numerical data
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Time Factors

Substances

  • RNA, Messenger