{Reference Type}: Journal Article
{Title}: Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.
{Author}: Her H;Rothamel KL;Nguyen GG;Boyle EA;Yeo GW;
{Journal}: Cell Genom
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 25
暂无{DOI}: 10.1016/j.xgen.2024.100603
{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.