# A powerful web-based discovery platform for rare disease genetics

> **NIH NIH R01** · BROAD INSTITUTE, INC. · 2020 · $701,649

## Abstract

PROJECT SUMMARY
 A fundamental challenge in human disease genetics is separating the small minority of variants that
underlie a disease phenotype from the overwhelming majority of variants that are irrelevant to the phenotype.
Resolving the genetic basis of rare diseases has been relatively fruitful despite this challenge, thanks to the
fact that they are primarily caused by loss of function variants in a single gene and to the tremendous
technological advances in DNA sequencing. However, despite many successes, the genetic basis of
thousands of Mendelian disorders remains unknown and hundreds of new Mendelian disorders are described
each year. Moreover, less than half of the Mendelian disorders studied are resolved after sequencing of
affected families.
 Based on our experience in diagnosing rare diseases and in developing research software in this
domain, we argue that existing commercial tools are both inadequate and expensive. Research pipelines for
rare disease require substantial computational expertise and the integration of diverse genome annotations
and algorithms for variant prioritization. The technical complexity of such pipelines inhibits discovery from
researchers with substantial disease knowledge yet limited computational resources or experience. Therefore,
our goal is to build a scalable, interactive, state-of-the-art software platform that will democratize the process of
gene discovery in studies of Mendelian and other rare diseases. Our first Specific Aim is to create
GxBrowse: an open source, interactive platform for rare disease discovery, drawing on the strengths
of GEMINI, xBrowse, and the Exome Aggregation Consortium, three widely used tools and resources
developed in our laboratories. Secondly, we will maximize GxBrowse’s performance, scalability, and
accessibility to facilitate future rare disease research, especially as research in this area transitions from
exome to whole genome sequencing. Lastly, we will provide innovative strategies for variant
interpretation, visualization and data sharing to dramatically increase the rate of diagnosis and gene
discovery.
 The GxBrowse platform will address fundamental analytical challenges in gene discovery for rare
Mendelian diseases, and make a powerful and scalable open-source toolkit for rare disease analysis
accessible to a wide range of researchers. We anticipate that GxBrowse will empower many research labs and
become invaluable to future discoveries in larger NIH-funded efforts such as the Centers for Mendelian
Genomics and the Undiagnosed Diseases Network.

## Key facts

- **NIH application ID:** 9963326
- **Project number:** 5R01HG009141-04
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Aaron R Quinlan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $701,649
- **Award type:** 5
- **Project period:** 2017-09-13 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963326

## Citation

> US National Institutes of Health, RePORTER application 9963326, A powerful web-based discovery platform for rare disease genetics (5R01HG009141-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9963326. Licensed CC0.

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