title: A growth curve model with fractional polynomials for analysing incomplete time-course data in microarray gene expression studies.
abstract: Identifying the various gene expression response patterns is a challenging issue in expression microarray time-course experiments. Due to heterogeneity in the regulatory reaction among thousands of genes tested, it is impossible to manually characterize a parametric form for each of the time-course pattern in a gene by gene manner. We introduce a growth curve model with fractional polynomials to automatically capture the various time-dependent expression patterns and meanwhile efficiently handle missing values due to incomplete observations. For each gene, our procedure compares the performances among fractional polynomial models with power terms from a set of fixed values that offer a wide range of curve shapes and suggests a best fitting model. After a limited simulation study, the model has been applied to our human in vivo irritated epidermis data with missing observations to investigate time-dependent transcriptional responses to a chemical irritant. Our method was able to identify the various nonlinear time-course expression trajectories. The integration of growth curves with fractional polynomials provides a flexible way to model different time-course patterns together with model selection and significant gene identification strategies that can be applied in microarray-based time-course gene expression experiments with missing observations.
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.forename: Jacob V B
authors.initials: JV
authors.lastname: Hjelmborg
authors.forename: Anders
authors.initials: A
authors.lastname: Clemmensen
authors.forename: Klaus Ejner
authors.initials: KE
authors.lastname: Andersen
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Petersen
authors.forename: Matthew
authors.initials: M
authors.lastname: McGue
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse