# Center for Integrated Approached to Undiagnosed Diseases

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $328,215

## Abstract

PROJECT SUMMARY
Undiagnosed diseases are likely to be determined by genetic, environmental, and developmental factors.
While some undiagnosed diseases will represent novel rare genetic syndromes with monogenic or oligogenic
etiologies and others will reflect rare manifestations of known diseases, many are likely to result from a more
analytically challenging combination of multiple genetic, environmental, and developmental factors. Whole
exome and whole genome sequencing are powerful tools with which to ascertain the genetic contributions to
undiagnosed diseases; however, these methods alone are unlikely to elucidate the basis for many, if not most,
undiagnosed diseases. Using an integrated, network-based, systems biology approach that incorporates not
only genetic variation data, but also gene expression, metabolomic, proteomic, and exposomic data, along with
careful deep phenotyping, has shown to be the most effective way to identify the pathways and mechanisms
responsible for many undiagnosed diseases. We will continue our integrated interdisciplinary research plan for
the Harvard Undiagnosed Disease Network Clinical Site (Harvard UDN-CS) that involves three Specific Aims:
 1) Ascertainment and clinical characterization - we will perform case ascertainment and phenotypic
 characterization for selected rare and undiagnosed disease states in adults and children;
 2) Genomic assessments - we will use patient and family member-derived DNA sequence, transcriptomic
 data, and clinical phenotype information to identify potentially causal DNA sequence variants, gene
 expression variation, and potentially causative pathway derangements; and
 3) Network approach to disease diagnosis - we will integrate other -omic data, including metabolomic,
 proteomic, and exposomic data, along with the candidate genetic variants into the comprehensive
 interactome, and thereby identify diseases or disease pathways in network proximity to the involved
 genes that may help identify potential pathobiological modules relevant to the etiology of the
 undiagnosed disease.
For probands accepted on or before June 30, 2022, this supplement will allow us to continue our work toward
meeting these specific aims and addressing the overall hypothesis in close collaboration with the UDN
Coordinating Center (UDN-CC) and other clinical sites in the UDN in order to develop and implement
assessment protocols of phenotype, environment, and genotype that will ultimately define the etiology and
treatment of undiagnosed diseases.

## Key facts

- **NIH application ID:** 10600194
- **Project number:** 3U01HG007690-08S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joseph Loscalzo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $328,215
- **Award type:** 3
- **Project period:** 2022-04-02 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600194

## Citation

> US National Institutes of Health, RePORTER application 10600194, Center for Integrated Approached to Undiagnosed Diseases (3U01HG007690-08S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10600194. Licensed CC0.

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