1. Exploratory bioinformatics study of lncRNAs in Alzheimer's disease mRNA sequences with application to drug development.
- Author
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Holden T, Nguyen A, Lin E, Cheung E, Dehipawala S, Ye J, Tremberger G Jr, Lieberman D, and Cheung T
- Subjects
- 5'-Nucleotidase genetics, Alzheimer Disease drug therapy, Amyloid beta-Protein Precursor genetics, Animals, Apolipoproteins E genetics, Computational Biology, Disease Models, Animal, Drug Discovery, Erythropoietin genetics, Fractals, Glycoproteins genetics, Humans, Intracellular Signaling Peptides and Proteins genetics, Mice, Neuropeptides genetics, Orexin Receptors genetics, Orexins, Presenilin-2 genetics, Receptors, Erythropoietin genetics, Sequence Analysis, RNA statistics & numerical data, Zebrafish, Alzheimer Disease genetics, RNA, Long Noncoding genetics, RNA, Messenger genetics
- Abstract
Long noncoding RNA (lncRNA) within mRNA sequences of Alzheimer's disease genes, namely, APP, APOE, PSEN1, and PSEN2, has been analyzed using fractal dimension (FD) computation and correlation analysis. We examined lncRNA by comparing mRNA FD to corresponding coding DNA sequences (CDSs) FD. APP, APOE, and PSEN1 CDSs select slightly higher FDs compared to the mRNA, while PSEN2 CDSs FDs are lower. The correlation coefficient for these sequences is 0.969. A comparative study of differentially expressed MAPK signaling pathway lncRNAs in pancreatic cancer cells shows a correlation of 0.771. Selection of higher FD CDSs could indicate interaction of Alzheimer's gene products APP, APOE, and PSEN1. Including hypocretin sequences (where all CDSs have higher fractal dimensions than mRNA) in the APP, APOE, and PSEN1 sequence analyses improves correlation, but the inclusion of erythropoietin (where all CDSs have higher FD than mRNA) would suppress correlation, suggesting that HCRT, a hypothalamus neurotransmitter related to the wake/sleep cycle, might be better when compared to EPO, a glycoprotein hormone, for targeting Alzheimer's disease drug development. Fractal dimension and entropy correlation have provided supporting evidence, consistent with evolutionary studies, for using a zebrafish model together with a mouse model, in HCRT drug development.
- Published
- 2013
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