Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences
Bioinformatics | Computational Biology | Genetics and Genomics | Integrative Biology | Systems Biology
Accurate transcription start site (TSS) annotations are essential for understanding transcriptional regulation and its role in human disease. Gene collections such as GENCODE contain annotations for tens of thousands of TSSs, but not all of these annotations are experimentally validated nor do they contain information on cell type-specific usage. Therefore, we sought to generate a collection of experimentally validated TSSs by integrating RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression (RAMPAGE) data from 115 cell and tissue types, which resulted in a collection of approximately 50 thousand representative RAMPAGE peaks. These peaks are primarily proximal to GENCODE-annotated TSSs and are concordant with other transcription assays. Because RAMPAGE uses paired-end reads, we were then able to connect peaks to transcripts by analyzing the genomic positions of the 3' ends of read mates. Using this paired-end information, we classified the vast majority (37 thousand) of our RAMPAGE peaks as verified TSSs, updating TSS annotations for 20% of GENCODE genes. We also found that these updated TSS annotations are supported by epigenomic and other transcriptomic data sets. To show the utility of this RAMPAGE rPeak collection, we intersected it with the NHGRI/EBI genome-wide association study (GWAS) catalog and identified new candidate GWAS genes. Overall, our work shows the importance of integrating experimental data to further refine TSS annotations and provides a valuable resource for the biological community.
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© 2022 Moore et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
DOI of Published Version
Moore JE, Zhang XO, Elhajjajy SI, Fan K, Pratt HE, Reese F, Mortazavi A, Weng Z. Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types. Genome Res. 2022 Feb;32(2):389-402. doi: 10.1101/gr.275723.121. Epub 2021 Dec 23. PMID: 34949670; PMCID: PMC8805725. Link to article on publisher's site
Moore JE, Zhang X, Elhajjajy SI, Fan K, Pratt HE, Reese F, Mortazavi A, Weng Z. (2021). Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types. Program in Bioinformatics and Integrative Biology Publications. https://doi.org/10.1101/gr.275723.121. Retrieved from https://escholarship.umassmed.edu/bioinformatics_pubs/174
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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License