A multi-omic Huntington's disease transgenic sheep-model database for investigating disease pathogenesis
journal contribution
posted on 2023-05-03, 18:49authored byEmily Mears, Renee Handley, Matthew Grant, Suzanne Reid, Benjamin Day, Skye Rudiger, Clive McLaughlan, Paul Verma, Simon Bawden, Stefano Patassini, Richard Unwin, Garth Cooper, James Gusella, Marcy MacDonald, Rudiger BrauningRudiger Brauning, Paul MacleanPaul Maclean, John Pearson, Henry Waldvogel, Richard Faull, Russell Snell
Background: The pathological mechanism of cellular dysfunction and death in Huntington’s disease (HD) is not well defined. Our transgenic HD sheep model (OVT73) was generated to investigate these mechanisms and for therapeutic testing. One particular cohort of animals has undergone focused investigation resulting in a large interrelated multi-omic dataset, with statistically significant changes observed comparing OVT73 and control ‘omic’ profiles and reported in literature.
Objective: Here we make this dataset publicly available for the advancement of HD pathogenic mechanism discovery.
Methods: To enable investigation in a user-friendly format, we integrated seven multi-omic datasets from a cohort of 5-year-old OVT73 (n = 6) and control (n = 6) sheep into a single database utilising the programming language R. It includes high-throughput transcriptomic, metabolomic and proteomic data from blood, brain, and other tissues.
Results: We present the ‘multi-omic’ HD sheep database as a queriable web-based platform that can be used by the wider HD research community (https://hdsheep.cer.auckland.ac.nz/). The database is supported with a suite of simple automated statistical analysis functions for rapid exploratory analyses. We present examples of its use that validates the integrity relative to results previously reported. The data may also be downloaded for user determined analysis.
Conclusion: We propose the use of this online database as a hypothesis generator and method to confirm/refute findings made from patient samples and alternate model systems, to expand our understanding of HD pathogenesis. Importantly, additional tissue samples are available for further investigation of this cohort.
Mears, E. R., Handley, R. R., Grant, M. J., Reid, S. J., Day, B. T., Rudiger, S. R., … Snell, R. G. (2021). A multi-omic Huntington’s disease transgenic sheep-model database for investigating disease pathogenesis. Journal of Huntington’s Disease, 10(4), 423-434. doi:10.3233/JHD-210482