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| Status |
Public on Jul 10, 2024 |
| Title |
Accurate isoform quantification by joint short- and long-read RNA-sequencing [short reads] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Accurate quantification of transcript isoforms is crucial for understanding gene regulation, functional diversity, and cellular behavior. Existing methods using either short-read (SR) or long-read (LR) RNA sequencing have significant limitations: SR sequencing provides high depth but struggles with isoform deconvolution, while LR sequencing offers isoform resolution at the cost of lower depth, higher noise, and technical biases. Addressing this gap, we introduce Multi-Platform Aggregation and Quantification of Transcripts (MPAQT), a generative model that combines the complementary strengths of different sequencing platforms to achieve state-of-the-art isoform-resolved transcript quantification, as demonstrated by extensive simulations and experimental benchmarks. Applying MPAQT to an in vitro model of human embryonic stem cell differentiation into cortical neurons, followed by machine learning-based modeling of mRNA abundance determinants, reveals the role of untranslated regions (UTRs) in isoform regulation through isoform-specific interactions with RNA-binding proteins that modulate mRNA stability. These findings highlight MPAQT's potential to enhance our understanding of transcriptomic complexity and underline the role of splicing-independent post-transcriptional mechanisms in shaping the isoform and exon usage landscape of the cell.
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| Overall design |
Gene expression profiling of human embryonic stem cells (HESC) before (day 0) and after undergoing Cortical neuron differentiation (day 41 and 61). Two replicates per condition.
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| Contributor(s) |
Apostolides M, Choi B, Navickas A, Saberi A, Soto LM, Goodarzi H, Najafabadi HS |
| Citation(s) |
39026819 |
| |
| Submission date |
Jul 05, 2024 |
| Last update date |
Aug 09, 2024 |
| Contact name |
Hamed S Najafabadi |
| E-mail(s) |
hamed.najafabadi@mcgill.ca
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| Organization name |
McGill University
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| Department |
Human Genetics
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| Lab |
Computational and Statistical Genomics Lab
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| Street address |
740 Dr. Penfield Avenue
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3A 0G1 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (6)
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| GSM8378902 |
Differentiated (day 41) - short reads - rep 2 |
| GSM8378903 |
Differentiated (day 61) - short reads - rep 1 |
| GSM8378904 |
Differentiated (day 61) - short reads - rep 2 |
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| This SubSeries is part of SuperSeries: |
| GSE271530 |
Accurate isoform quantification by joint short- and long-read RNA-sequencing |
|
| Relations |
| BioProject |
PRJNA1132172 |
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