# Advancing the cloud-based data access and interoperability infrastructure of the INCLUDE data ecosystem

> **NIH NIH U2C** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $330,890

## Abstract

PROJECT SUMMARY
The overarching goal of the INCLUDE Data Hub is to serve all people with Down syndrome (DS) by accelerating
the pace of discoveries into the mechanisms by which trisomy 21 (T21) predisposes these individuals to a wide
range of comorbidities that shorten their life expectancy and diminish their quality of life. Over the last few
decades, the life expectancy for people with DS has significantly increased, and epidemiological studies reveal
that T21 causes a different disease spectrum, protecting these individuals from developing certain conditions,
such as most solid malignancies (1,2), while strongly predisposing them to others, such as Alzheimer’s disease
(AD) (3), congenital heart disease (CHD) (4), leukemias (1), autoimmune disorders (5–17), and neurological
conditions such as autism and seizure disorders (18–22). With the exception of their increased risk of
developing AD, which has been linked to the presence of the APP gene on chromosome 21 (3), little is known
about the mechanisms underlying this differential clinical profile. Moreover, there is massive phenotypic
variation among individuals with T21, which suggests the existence of factors modulating the effects of the extra
chromosome, such as genetic variation, epigenetic modifiers, varying endotypes modulating the transcriptome,
proteome and metabolome, lifestyle and environmental factors, or even perhaps the microbiome. Therefore,
elucidating the mechanisms driving and modulating DS comorbidities will serve not only the six million people
worldwide with DS alive today, but also millions of individuals affected by these comorbidities in the typical
population.
The INCLUDE Data Hub has reached a significant milestone of an MVP launch featuring both open-access and
controlled data (via Kids First Gen3) on 21 March 2022. Here, we propose “Advancing the cloud-based data
access and interoperability infrastructure of the INCLUDE data ecosystem” to empower more authorized
researchers to access controlled INCLUDE data. This capability is beyond the scope of what we envision in the
original INCLUDE DAPI proposal.
Our focus is to develop and implement Clearinghouse software and integrate it with the DRS Server already
developed for INCLUDE. The Clearinghouse receives and interprets the RAS Passport, and the custom visas
contained, to ascertain the ability of a user to access controlled data (importantly, authorization continues to be
governed by dbGaP). We will also provide feedback and advance the GA4GH specification pertinent to this
effort, to drive these standards towards alignment with the INCLUDE Data Hub strategy.

## Key facts

- **NIH application ID:** 10596806
- **Project number:** 3U2CHL156291-02S3
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Jack DiGiovanna
- **Activity code:** U2C (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $330,890
- **Award type:** 3
- **Project period:** 2022-05-03 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596806

## Citation

> US National Institutes of Health, RePORTER application 10596806, Advancing the cloud-based data access and interoperability infrastructure of the INCLUDE data ecosystem (3U2CHL156291-02S3). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10596806. Licensed CC0.

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