The Human Brainome: Genome, Transcriptome and Proteome Interaction in Human Cortex
EMSL Project ID
47298
Abstract
Our Human Brainome project seeks to define the genome-transriptome-proteomephenome interactions in the cortexes of normally aged human brains and brains affected by neurodegenerative disease. We hypothesize that the current accepted approach for discovering novel genetic risk loci by looking at a single layer of information (genotypes) is lacking power and taking a more systems-wide approach might increase the success of finding novel targets. We intend upon comparing our genotype information (~ 1.8 million single nucleotide polymorphisms) and our expression information (~ 46,000 transcripts) with a novel proteomics dataset generated by running Liquid Chromatography coupled online with high mass accuracy Mass Spectrometry (LC- MS, providing quantification of ~2000-3000 proteins). We will look at both single correlative cis and trans relationships (i.e. DNA change affects downstream regulation of one transcript or protein), as well as perform analyses to understand the networks of relationships occurring both at the transcriptome and proteome level. In this project we seek to define the effects of DNA variation on human cortical expression with an emphasis on the DNA variation that is impinging on proteome expression changes relevant to the pathogenesis of Alzheimer’s disease. If we achieve our aims we will know specifically which variant or group of variants are changing protein expression levels. This information will help us to define the downstream significance of DNA risk variation in Alzheimer’s disease, which might aid in the discovery of novel biomarkers and therapies for this devastating illness.
Project Details
Start Date
2012-03-21
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator