# Recovering Proteoforms from Cardiovascular Omics Datasets: A Multi-omics Secondary Analysis

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $116,625

## Abstract

PROJECT SUMMARY
Large-scale omics techniques including proteomics and RNA-seq have become important tools to identify
disease mechanisms and therapeutic targets. However, these experiments have largely not considered
“proteoforms” - protein variants coded by the same gene such as through alternative splicing and post-
translational modifications that can serve different cellular functions and whose distributions are often
permuted in disease. In the heart in particular, alternative splicing is implicated in broad pathological
processes in heart failure and cardiomyopathy, but at present we have a poor understanding of the
expression status and molecular functions of many alternative splice isoform products at the protein level.
 Recently we have developed and optimized a computational pipeline which can integrate information
from RNA-seq and proteomics data to recover lost protein isoform information from proteomics data. Our
goal now is to perform a targeted secondary analysis of publicly available quantitative proteomics data on
heart diseases that are housed in persistent data repositories. Specifically, Aim 1 will (i) identify and quantify
alternative splice isoforms in heart failure and atrial fibrillation proteomics data, by using custom sequence
databases constructed from RNA-seq data; and (ii) determine the intersections between AS isoforms with
PTM sites at regulatory hotspots, with the aid of mass-tolerant open-search algorithms that can recover
unexpected PTMs in proteomics data.
 By reanalyzing existing datasets with our pipeline we aim to extract isoform-level knowledge on
existing data, which we are confident will have a strong likelihood to open unforeseen avenues into the
research of heart diseases, and also add value to the existing rich data resources in our research community.

## Key facts

- **NIH application ID:** 9879513
- **Project number:** 1R21HL150456-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Maggie Lam
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $116,625
- **Award type:** 1
- **Project period:** 2020-01-15 → 2021-12-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9879513

## Citation

> US National Institutes of Health, RePORTER application 9879513, Recovering Proteoforms from Cardiovascular Omics Datasets: A Multi-omics Secondary Analysis (1R21HL150456-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9879513. Licensed CC0.

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