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Sequential Penta-Omic Extraction Method Using Single Biospecimens of Post-mortem Human Brain

Preprint Created on 29 Jun 2026 bioRxiv

A multi-omic approach utilizing a single biospecimen is important to avoid intra-sample heterogeneity associated with testing multiple omic single-samples, and for more efficient use of small volumes of precious biopsies (<30 mg). This is especially true for the microanatomy of post-mortem human brain samples. Using post-mortem human brain biospecimens from the NIH NeuroBioBank, a penta-omic sequential extraction method is described, Simultaneous Metabolomic, Proteomic, Lipidomic, DNA, RNA Extraction (SiMPL-DREx). Each sequential omic extract was compared to those obtained by the gold standard single omic method. Preserving RIN is critical for brain and tissue banks, as it is a primary measure of tissue quality. For all five omic extracts, the tissue integrity numbers and omic profiles did not significantly differ from those obtained by the respective omic gold standard method. Unlike past multi-omic studies, this study quantified the relative solvent percentages and upstream losses for both the organic and aqueous phases, confirming an omics loss of under 5%.

Lyon, S. P., Ehrmann, B. M., Webb, T. S., Arciniega, C., Herring, L. E., Guo, S., Parnham, S., Scott, W. K., Mieczkowski, P. A., Macdonald, J. M.

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