Validation of penta-omic assays in brain tissue and identification of markers of tissue and -omic data quality

PROJECT SUMMARY There are hundreds of studies of Alzheimer’s disease, Alzheimer’s disease-related dementias, and other neurodegenerative diseases comparing post-mortem (PM) human brain tissues obtained from human brain repositories. Current approaches that compare multiple, separately measured, -omic profiles studies introduce

variability from using multiple samples. Thus, a multi-omics approach that can utilize a single biospecimen is needed. We have developed a penta-omic extraction method for frozen tissue and propose a proof-of-concept study. This effort would create the first penta-omic database, utilizing normal PM human brain tissue from the

NIH NeuroBioBank. A new penta-omic simultaneous metabolomic, proteomic, lipidomic, DNA, RNA extraction method called SiMPL-DREx will be applied to a single tissue sample which will minimize the heterogeneity associated with testing multiple samples. SiMPL-DREx has added value because it more efficiently uses small

volume, highly requested brain tissue. PM tissue selection is generally based entirely on a single quality control measure, RNA integrity number (RIN), obtained from a single tissue sample, usually the occipital pole (OP). Of the four -omic macromolecules extracted with SiMPL-DREx, RNA is the most labile primarily due to the universal

distribution of RNase in the body. Tissue with RIN >7 is highly desirable for genomic and transcriptomic studies, yet how the overall quality of the metabolome, proteome, and lipidome (MPL) varies as a function of RIN has never been fully investigated. Tissues with RIN