Abstract
Alzheimer’s disease (AD) is the most common type of neurodegenerative diseases. There are over 44 million people living with the disease worldwide. While there are currently no effective treatments for AD, induced pluripotent stem cell-derived brain organoids have the potential to provide a better understanding of Alzheimer’s pathogenesis. Nevertheless, developing brain organoid models is expensive, time consuming and often does not reflect disease progression. Using accurate and inexpensive computer simulations of human brain organoids can overcome the current limitations. Induced whole brain organoids (aiWBO) will greatly expand our ability to model AD and can guide wet lab research. In this study, we have successfully developed and validated artificially induced a whole brain organoid platform (NEUBOrg) using our previously validated machine learning platform, DeepNEU (v6.1). Using NEUBorg platform, we have generated aiWBO simulations of AD and provided a novel approach to test genetic risk factors associated with AD progression and pathogenesis.
Highlights
The modern era of human stem cell research was launched with a publication by Professor Yamanaka’s group in 2007 (Takahashi et al, 2007)
The probability that the expression of all (N = 10) Alzheimer’s Disease (AD) concepts were predicted by chance alone using the binomial test is 0.015
While the AD simulations produced some significant variability when compared with the aiWBO simulation outputs, the AD simulations correctly predicted the expression of 48 elements consistent with a pattern seen in a whole brain organoid and seven elements suggesting the expression of a compensated metabolic alkalosis and respiratory acidosis
Summary
The modern era of human stem cell research was launched with a publication by Professor Yamanaka’s group in 2007 (Takahashi et al, 2007). This landmark paper demonstrated conclusively that human fibroblasts could be transformed, with four transcription factors and optimal conditions, into cells closely resembling human pluripotent stem cells (hPSC). These transformed cells have become widely referred to as induced pluripotent stem cells (iPSC). While still in its infancy, the science of human organoids has been used successfully to develop multiple organoid types including intestine, heart, pancreas, liver, lung, and brain to name a few (Kim et al, 2020)
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