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The Ramp Atlas: facilitating tissue and cell-specific ramp sequence analyses through an intuitive web interface.
Justin B Miller1, Taylor E Meurs2, Matthew W Hodgman1
1Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40504, USA.
NAR Genomics and Bioinformatics
|June 6, 2022
Summary
Tissue-specific codon adaptiveness influences gene expression by altering ramp sequences, which are regulatory regions at the 5' end of genes. The Ramp Atlas tool analyzes these dynamic sequences across various tissues and cell types.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Ramp sequences, characterized by lower translational efficiency at a gene's 5' end, paradoxically enhance overall gene expression by minimizing ribosomal collisions.
- The existence and impact of these sequences are primarily studied in a general context, with limited understanding of their tissue-specific variations.
Purpose of the Study:
- To investigate how tissue-specific codon adaptiveness affects the presence and function of ramp sequences.
- To conduct a comprehensive analysis of ramp sequences across diverse human tissues and cell types.
- To develop a resource for exploring and analyzing tissue-specific ramp sequences.
Main Methods:
- Analysis of codon adaptiveness across different tissues and cell types to identify variations in ramp sequences.
- Development and utilization of The Ramp Atlas, a web-based tool for querying and calculating tissue-specific ramp sequences for thousands of genes.
- Application of The Ramp Atlas to identify tissue-specific ramp sequences in SARS-CoV-2 and human entry factor genes.
Main Results:
- Identified 3108 genes exhibiting tissue- and cell type-specific ramp sequences, correlating with increased gene expression in those contexts.
- The Ramp Atlas provides access to precomputed ramp sequences for 18,388 genes across 62 tissues and 66 cell types.
- Discovered tissue-specific ramp sequences in seven SARS-CoV-2 genes and seven human SARS-CoV-2 entry factor genes, potentially explaining viral tropism.
Conclusions:
- Relative codon adaptiveness is a key determinant of tissue-specific ramp sequence formation, independent of genetic code alterations.
- The Ramp Atlas serves as a valuable resource for researchers to explore gene regulation through the lens of tissue-specific ramp sequences.
- Understanding tissue-specific ramp sequences offers new avenues for investigating gene expression, viral pathogenesis, and potential therapeutic strategies.
