Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.
Hsuanlin Her, Katherine L Rothamel, Grady G Nguyen, Evan A Boyle, Gene W Yeo
Cell genomics · 2024 · Vol. 4 (7) · pp. 100603
Abstract
The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets are multivariate, and each RBP suffers non-uniform signal-to-noise ratio. To address this, we developed Mudskipper, a versatile computational suite comprising two components: a Dirichlet multinomial mixture model to account for the multivariate nature of ABC datasets and a softmasking approach that identifies and removes non-specific protein-RNA interactions in RBPs with low signal-to-noise ratio. Mudskipper demonstrates superior precision and recall over existing tools on multiplex datasets and supports analysis of repetitive elements and small non-coding RNAs. Our findings unravel splicing outcomes and variant-associated disruptions, enabling higher-throughput investigations into diseases and regulation mediated by RBPs.
Potentially related datasets 7
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
| Accession | Source | Title |
|---|---|---|
| GSE20553613 | GSE · GEO GEO ↗ | No title in the index |
| GSE205536 | GSE · GEO GEO ↗ | Multiplexed transcriptome discovery of RNA binding protein binding sites by antibody-barcode eCLIP |
| ENCSR950WBG | ENCSR · ENCODE | eCLIP control experiment on K562 against SLBP |
| ENCSR137HKS | ENCSR · ENCODE | shRNA knockdown against PRPF8 in K562 cells followed by RNA-seq. (PRPF8_BGKLV19) |
| ENCSR000AEL | ENCSR · ENCODE | No title in the index |
| ENCSR081XRA | ENCSR · ENCODE | shRNA knockdown against SF3B4 in K562 cells followed by RNA-seq. (SF3B4-LV08) |
| ENCFF133KON | ENCFF · ENCODE | No title in the index |
Funding 3 grants
| Grant | Funder |
|---|---|
| U24 HG009889 | NHGRI NIH HHS (United States) |
| R01 HG004659 | NHGRI NIH HHS (United States) |
| T32 CA067754 | NCI NIH HHS (United States) |