# Integrating multiomic analyses for gene discovery andgenetic diagnosis of Mendelian myopathies

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $173,880

## Abstract

PROJECT SUMMARY/ABSTRACT
This NIH K23 proposal details a comprehensive five-year training plan for mentored patient-oriented research
career development and research to address a major problem in neuromuscular medicine. Over half of patients
with clinically suspected Mendelian myopathies do not have a molecular diagnosis, largely due to two challenges:
detecting pathogenic non-coding variants, and resolving the pathogenicity of ultra-rare missense variants. Here
I propose to address this challenge through the application of genome sequencing (Aim 1), transcriptome
sequencing (Aim 2), and proteomic (Aim 3) methods to evaluate the strengths and weakness of each method
and to improve the diagnostic yield from a cohort of approximately 200 individuals with unsolved Mendelian
myopathies. I hypothesize that since the genetic architecture of Mendelian myopathies implicates large genes
that genome sequencing combined with RNA-sequencing (RNA-seq) and proteomics can mitigate the current
low diagnostic yield after clinical evaluation of Mendelian myopathies. Through these approaches, I will define
best practices in applying technologies in the diagnostic evaluation, discover novel disease variants and genes,
and expand our understanding of the genetic architecture of these heterogeneous disorders.
Gaining the analytical skills to evaluate the real-world application of multiomic methods will complement both my
prior expertise in gene discovery for neurologic disorders and my clinical training in neuromuscular medicine. I
am uniquely positioned within the collaborative environment between Brigham and Women’s Hospital, Boston
Children’s Hospital, Broad Institute, and Harvard Medical School to facilitate my transition to an independent
physician-scientist with a long-term translational research goal of developing a center of excellence in the clinical
characterization, molecular diagnosis, and evaluation of targeted gene therapy candidates for patients with
Mendelian myopathies.

## Key facts

- **NIH application ID:** 10785664
- **Project number:** 1K23AR083505-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Vijay S Ganesh
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $173,880
- **Award type:** 1
- **Project period:** 2024-02-16 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785664

## Citation

> US National Institutes of Health, RePORTER application 10785664, Integrating multiomic analyses for gene discovery andgenetic diagnosis of Mendelian myopathies (1K23AR083505-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10785664. Licensed CC0.

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