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Transcription Start Site Mapping Using Super-low Input Carrier-CAGE
Published on: June 26, 2019
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Using long-read CAGE sequencing to profile cryptic-promoter-derived transcripts and their contribution to the
Ju Heon Maeng1,2, H Josh Jang1,2, Alan Y Du1,2
1Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Genome Research
|December 8, 2023
Summary
New methods enhance the detection of tumor-specific antigens derived from transposable elements (TEs). This advance in cancer immunotherapy research identifies novel targets, especially in tumors with low mutation rates.
Area of Science:
- Genomics
- Immunology
- Cancer Research
Background:
- The noncoding genome can generate unannotated proteins acting as antigens, often due to epigenetic reactivation of transposable elements (TEs) in tumors.
- TEs can create alternative promoters in tumors, leading to transcripts encoding tumor-specific unannotated proteins, which are potential cancer antigens.
Purpose of the Study:
- To develop and validate advanced genomics and computational tools for improved detection of TE-derived tumor antigens.
- To enhance immunopeptidome analysis by incorporating TE and other tumor transcripts into proteome databases for cancer immunotherapy.
Main Methods:
- Combined CAGE technology with full-length long-read transcriptome sequencing (LRCAGE).
- Developed novel computational tools to improve immunopeptidome detection.
- Applied LRCAGE to human lung cancer cell line H1299 and analyzed HLA-pulldown LC-MS/MS data.
Main Results:
- Long-read technology improved the mapping of low-mappability promoters and ensured accurate 5' transcript structure construction.
- Augmenting proteome databases with newly identified transcripts enabled the detection of noncanonical antigens.
- Epigenetic treatment increased noncanonical antigens, particularly those from TE transcripts, suggesting expanded targetable antigen pools.
Conclusions:
- The developed LRCAGE method and computational tools significantly improve the detection of noncanonical antigens, especially those derived from transposable elements.
- This approach holds promise for improving cancer immunotherapy by identifying novel, shared tumor antigens, particularly for cancers with low mutational burden.
