MrHAMER2: high-accuracy long-read RNA sequencing to decode isoform-specific variation in viral transcripts during latency
Gallardo, C. M.; Albert, J. L.; Qazi, A. A.; Ventura, R. L.; Deshmukh, S.; Beliakova-Bethell, N.; Torbett, B. E.
Show abstract
Alternative splicing (AS) greatly expands the repertoire of proteins encoded by the human genome. Viruses have been shown to hijack AS cellular pathways to sustain replication or lead to latency. In HIV-1 infection, the virus integrates into the host genome, becoming a transcriptional unit that directly engages in AS to regulate its gene expression. Sequencing advances have enabled insights into HIV-1 gene expression dynamics during productive replication. However, viral isoform dynamics during latency remain largely uncharacterized due to the low abundance of spliced viral transcripts in associated CD4+ T cell subsets, making their accurate detection and quantification challenging. MrHAMER2 is a high-accuracy long-read RNA sequencing method that leverages dual Unique Molecular Identifier (UMI) tagging of cDNA to accurately capture and quantify full-length isoforms with high dynamic range and 99.968% single-nucleotide accuracy. We used MrHAMER2 to decode the spliced HIV-1 transcriptome in a primary CD4+ T cell model of latency and showed substantial changes in viral isoforms bearing intron retentions accompanied by changes in their potential to generate translatable protein.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- SARSeq, a robust and highly multiplexed NGS assay for parallel detection of SARS-CoV2 and other respiratory infections 96%
- In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia 96%
- Demultiplexing and barcode-specific adaptive sampling for nanopore direct RNA sequencing 96%
Similar papers in this journal
- A systematic benchmark of Nanopore long read RNA sequencing for transcript level analysis in human cell lines 95%
- Absolute quantitative and base-resolution sequencing reveals comprehensive landscape of pseudouridine across the human transcriptome 95%
- Single molecule co-occupancy of RNA-binding proteins with an evolved RNA deaminase 94%
Similar papers in this journal
Similar papers in this journal
- MrHAMER yields highly accurate single molecule viral sequences enabling analysis of intra-host evolution 96%
- Nanopore ReCappable Sequencing maps SARS-CoV-2 5' capping sites and provides new insights into the structure of sgRNAs 96%
- Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting in Theilovirus 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.