Project Grant R01GM164526

The National Institute of General Medical Sciences awarded Worcester Polytechnic Institute $431,535 on August 10, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop and validate integrative machine learning methods for characterizing alternatively spliced isoforms of RNA-binding proteins and their functional roles in gene expression, RNA metabolism, and cellular homeostasis.

The project will combine transcriptomic, proteomic, interactomic, and structural data with deep learning and semi-supervised learning techniques across three aims. Aim 1 develops machine learning strategies to predict the physiological stability of alternative RNA-binding protein isoforms. Aim 2 introduces an alternative splicing impact factor to quantify functional effects of splicing events on RNA-binding capacity and expands predictions of RNA-binding sites. Aim 3 applies these tools to medically relevant RNA-binding proteins and performs isoform-specific biochemical and RNA-binding experiments to validate model predictions. The work will produce a framework to interpret biological consequences of RNA-binding protein isoforms, with implications for understanding post-transcriptional regulation and revealing new disease mechanisms and therapeutic interventions.

Performance occurs in Worcester, Massachusetts. The period of performance runs through April 30, 2030. This is a Project Grant, a standard assistance type under NIGMS supporting investigator-initiated basic biomedical research that advances understanding of human health and disease.