# VARIATION AND REGULATION OF ALTERNATIVE SPLICING IN HUMAN TRANSCRIPTOMES

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $369,600

## Abstract

PROJECT SUMMARY
The central objective of this renewal R01 project is to elucidate the variation and regulation of alternative
splicing (AS) in human transcriptomes. Eukaryotic cells generate astonishing regulatory diversity and complex
phenotypes from a finite set of genes. AS of precursor mRNA is a mechanism essential for generating this
regulatory diversity. Almost all multi-exon human genes are alternatively spliced. Widespread changes in AS
occur between species, within human populations, in response to developmental signals and environmental
perturbations, and in disease pathogenesis. Despite the importance of AS in gene regulation and disease, as
well as extensive interest and research activities in this field, there remain many open questions and significant
knowledge gaps regarding the landscape, regulation, and functional consequence of AS variation in human
transcriptomes. Powerful sequencing technologies for characterizing transcriptome complexity (RNA-seq) and
protein-RNA interaction (CLIP-seq), as well as the vast amounts of data continuously deposited into the public
domain, create exciting and unprecedented opportunities for studies of AS. This proposal integrates data-
driven research leveraging big transcriptome data with hypothesis-driven research using molecular and
genomic tools. In three aims, we will investigate the evolution of AS in primates
(Aim 1), the genetic variation
and phenotypic association of AS in human populations (Aim 2), and epigenetic regulation of AS across human
tissues and cell states (Aim 3).
We will also develop and disseminate innovative computational and statistical
methods for analyzing AS using large, heterogeneous sequencing datasets. As in our previous funding cycle,
we will tap into our extensive network of expert collaborators to amplify the impact of our work and pursue new
research opportunities within and beyond the scope of the proposed project. Collectively, our research will
generate significant novel insights into the variation, regulation, and function of AS, and create broadly
applicable computational tools for studying AS variation and mRNA isoform complexity in diverse biomedical
disciplines.

## Key facts

- **NIH application ID:** 9912772
- **Project number:** 5R01GM088342-11
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Yi Xing
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,600
- **Award type:** 5
- **Project period:** 2010-04-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912772

## Citation

> US National Institutes of Health, RePORTER application 9912772, VARIATION AND REGULATION OF ALTERNATIVE SPLICING IN HUMAN TRANSCRIPTOMES (5R01GM088342-11). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9912772. Licensed CC0.

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