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Friday, December 3 • 10:45am - 10:55am
OP 22 - The Ramp Atlas: Facilitating tissue-specific ramp sequence analyses across humans and SARS-CoV-2

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The Ramp Atlas: Facilitating tissue-specific ramp sequence analyses across humans and SARS-CoV-2

Presenting Author: Justin Miller, University of Kentucky; Brigham Young University

Taylor Meurs, Brigham Young University
Matthew Hodgman, University of Kentucky
Benjamin Song, Brigham Young University
Kyle Miller, Utah Valley University
Mark Ebbert, University of Kentucky
John Kauwe, Brigham Young University
Perry Ridge, Brigham Young University

Abstract: Ramp sequences are essential genetic regulatory regions that counterintuitively function to slow initial translation, which ultimately maximizes overall translational efficiency by evenly spacing ribosomes and limiting downstream ribosomal collisions. Since widespread tissue-specific differences in relative codon adaptiveness occur, we predicted that the existence of a gene-specific ramp sequence would change between tissues without altering the underlying genetic code and would ultimately result in differential tissue-specific gene expression. Here, we present the first comprehensive analysis of tissue-specific ramp sequences, and report 3,108 genes with ramp sequences that change between tissues. The Ramp Atlas (https://ramps.byu.edu/) is an accompanying web portal that shows that the presence of a ramp sequence significantly correlates with higher gene expression in The Functional Annotation of Mammalian Genomes (FANTOM5) dataset (odds=1.1152; p-value=3.00x10-99), The Genotype-Tissue Expression (GTEx) Project dataset (odds=1.1578; p-value=9,48x10-155), The Human Protein Atlas dataset (odds=1.1947; p-value=1.27x10-306), and a consensus dataset (odds=1.1477; p-value=1.00x10-254). We also identified seven SARS-CoV-2 genes and seven human SARS-CoV-2 entry factor genes with tissue-specific ramp sequences that are present more frequently in tissues that the virus is known to infect (p-value=0.009918), which may help explain viral proliferation within those tissues. The Ramp Atlas facilitates wider adoption and application of ramp sequences through interactive graphics and an online programmatic interface. We propose that future ramp sequence calculations should consider ramp sequence variability that may occur within an organism based on tissue-specific codon optimality, and variable ramp sequences might be an additional mechanism for regulating tissue and cell type-specific differential gene expression that warrants further exploration.

avatar for Justin Miller

Justin Miller

University of Kentucky

Friday December 3, 2021 10:45am - 10:55am MST
Ballroom Salon 1