B2195 - Comparison of a developmental time series of expression against the expression individuals with autism spectrum disorder - 06/03/2014

B number: 
B2195
Principal applicant name: 
Dr Isaac Kohane (Harvard Medical School, Boston, USA)
Co-applicants: 
Title of project: 
Comparison of a developmental time series of expression against the expression individuals with autism spectrum disorder.
Proposal summary: 

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.

Date proposal received: 
Tuesday, 4 March, 2014
Date proposal approved: 
Thursday, 6 March, 2014
Keywords: 
Autism
Primary keyword: 
Gene Expression