B2195 - Comparison of a developmental time series of expression against the expression individuals with autism spectrum disorder - 06/03/2014
This is a very simple and brief study that is a follow-on to a study that we published previously on gene
expression in individuals with autism spectrum disorder (Kong SW, Collins CD, Shimizu-Motohashi Y,
Holm IA, Campbell MG, Lee I-H, et al. (2012): Characteristics and predictive value of blood
transcriptome signature in males with autism spectrum disorders. PLoS ONE. 7:e49475.) that we have
appended to this application. The aim of this study is to identify the developmental location of every one
of our subjects with Autism Spectrum Disorder (ASD) in gene transcriptome space. We hypothesize that
individuals with more severe autistic features will be more delayed (in their transcriptomic age relative to
their chronological age) than those who have less severe features (against the ADI/ADOS metrics that we
have for each subject). We will proceed with creating a principal component analysis of the ALSPAC
individuals based on the rank normalized expression data. This will provide a multidimensional map of
development of expression for these individuals. The expression data of the ASD individuals will be also
rank normalized and then these individuals will be projected into the ALSPAC expression space for those
genes present on both platforms used (for the ASD study and the ALSPAC study). Prior studies we have
conducted suggest that the effect of age on transcription will be located in the first two principal
components which will allow us to measure the developmental displacement of each ASD individual
relative to the ALSPAC group. We will have to examine gender as a confounding variable as well as the
scores of the SCDC questionnaire for ALSPAC subjects.