Presenters: Taylor Meurs, College of Life Sciences, Biology
Authors: Taylor Meurs, Matthew Hodgman, Benjamin Song
Faculty Advisors: Justin Miller, College of Life Sciences, Biology; John Kauwe, College of Life Sciences, Biology
Institution: Brigham Young University
Tissues and cell types utilize different codons and tRNAs to promote unique protein expression. Ramp sequences of slowly translated codons at the beginning of genes increase protein expression by augmenting translational efficiency, gene expression, and mRNA stability. While ramp sequences could affect tissue and cell type-specific protein expression, this relationship has never been analyzed. The recently developed ExtRamp software uses codon composition to identify ramp sequences, allowing for novel analyses. We applied this algorithm to the Human Protein Atlas, a widely used dataset of healthy human tissue and cell type expression, to identify ramp sequences across 10,456 genes in 44 tissues and 66 cell types. We present this data and statistical analyses for query on the Ramp Atlas webserver (https://ramps.byu.edu). Embedded within the Ramp Atlas is ExtRamp Online, a user-friendly interface to run the ExtRamp software quickly with options to use tissue-specific codon usage biases for additional accuracy. Using tissue and cell type-specific codon usage biases, we extracted ramp sequences that appeared in 23.5% and 22.5% of genes, respectively. The percentage of ramps across tissues and cell types were significantly different (p-value=1.86 x 10-24, 6.06 x 10-20), suggesting that codon composition and tRNA levels play a more significant role than previously thought in increasing translational efficiency and protein expression within different tissues and cell types. Additionally, we identified 21 genes that exhibit significant positive correlation between protein expression and ramp sequence presence. Whether a gene has a ramp sequence can suggest its expression level and importance in specific tissues and cell types. Similarly, a variant that creates or destroys a ramp sequence could significantly affect protein expression and thus disease development. We anticipate that the Ramp Atlas will facilitate increased understanding of the role of ramp sequences in expression, tissue and cell type-specific reactions to drugs, variant pathogenicity, and disease.