Develop new bioinformatics infrastructures and computational tools for epitranscriptomics data

Project Summary Dynamic mRNA modifications, such as the m6A-dependent regulation at the mRNA level, add a critical new dimension to post-transcriptional regulation of gene expression. The rapid development of sequencing technologies has transformed the field of epitranscriptomics studies by resulting in the successful profiling transcriptome-wide RNA modifications under different states and conditions. They hold the promise to reveal regulatory machinery of RNA modifications, which contributes to almost every phase of mRNA metabolism and function, thereby impacting diverse biological processes. How- ever, analytical developments in epitranscriptomics lag far behind the pace of technological discovery, and the bioinformatic infrastructure available for epitranscriptomic studies remains limited. The overar- ching goal of this proposal is to address three most pressing challenges facing profiling and interpreting epitranscriptomics. Specifically, we will achieve the following aims: Aim1. Develop statistical methods for RNA modification detection at single nucleotide resolution. Aim 2. Develop computational meth- ods for cell type-specific methylation analysis. Aim 3. Develop web servers that enable integrating RNA modification with a rich catalog of genomics features. All the methods will be implemented in user-friendly software and disseminated to the scientific community. Successful achievement of all aims will dramatically increase the power of epitranscriptomes analysis, leading to better understand- ing of regulatory mechanisms in RNA modifications and their implications in phenotypes and human diseases.