# Center for Undiagnosed Diseases at Stanford

> **NIH NIH U01** · STANFORD UNIVERSITY · 2020 · $50,000

## Abstract

Abstract
The Undiagnosed Diseases Network (UDN) has increased access for patients with undiagnosed diseases to
the nation’s leading clinicians and scientists. Phase II of the Network will facilitate the transition of UDN efforts
toward sustainability, through the expansion of clinical sites, refinement of methods, and integration with
regular clinical practice. Here, we propose a program of study that will (1) facilitate timely, accurate diagnosis
of patients with undiagnosed diseases; (2) improve diagnostic rates through novel approaches to data analysis
and integration; and (3) explore underlying mechanisms of disease to accelerate therapeutic drug discovery. In
Aim 1, we propose to evaluate patients referred to the UDN through a protocol that includes pre-visit chart
review and genetic counseling followed by an individualized visit during which standardized phenotypic and
environmental data are collected. Biosamples facilitate genomic, multi-omic, and cellular evaluation of disease.
Expansion of fibroblasts and, in selected cases, generation of induced Pluripotent Stem Cell (iPSC) lines
facilitates scientific investigation of the underlying diseases. We will expand our program of patient outreach,
particularly to under-served populations. We will extend our UDN-based genomic medicine educational
program both in scope and by broadening its eligibility. In Aim 2, we propose to develop and implement novel
methods in areas of high potential to increase diagnostic yield. This includes algorithms for the detection of
small genomic insertions and deletions as well as large scale structural variation. We will develop alignment
algorithms using graph reference genomes and promote the use of long-read sequencing technologies. We will
apply machine learning to the systematic integration of RNA sequencing, metabolomic, and phenotypic data
with the electronic medical record and the entire medical literature to improve diagnostic yield. In Aim 3, we
propose to facilitate diagnosis through enhanced cellular and model organisms phenotyping. We will
implement immunomic and metagenomic approaches such as T cell, B cell and unknown organism
sequencing for undiagnosed cases. We will utilize methods for moderate- and high-throughput phenotyping of
iPS-derived cells and promote novel drug discovery via high throughput drug screening both with FDA-
approved drugs and large scale small molecule libraries. Beyond Phase II, Stanford Medicine has made a
strong commitment to the continuation of the Center for Undiagnosed Diseases at Stanford through a multi-
million dollar institutional commitment. In summary, we aim to build on the success of Phase I of the UDN by
streamlining processes, maximizing collaboration and outreach, optimizing computational algorithms,
extending scientific investigation towards therapeutic discovery, and promoting engagement of hospital
leaders, clinicians, scientists, policy-makers, and philanthropists to ensure this national resource is sust...

## Key facts

- **NIH application ID:** 10124880
- **Project number:** 3U01HG010218-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Euan A Ashley
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,000
- **Award type:** 3
- **Project period:** 2018-09-21 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124880

## Citation

> US National Institutes of Health, RePORTER application 10124880, Center for Undiagnosed Diseases at Stanford (3U01HG010218-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10124880. Licensed CC0.

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