# Topological Mapping of Immune, Microbiota, Metabolomic and Clinical Phenotypes to Reveal ME/CFS Disease Mechanisms - Clinical Research Project

> **NIH NIH U54** · JACKSON LABORATORY · 2021 · $658,832

## Abstract

PROJECT SUMMARY CLINICAL RESEARCH PROJECT
The goal of the Clinical Project is to generate and integrate a complex network of clinical, immunologic,
metabolic, and microbiome datatypes on the ME/CFS etiology to engender hypotheses on immune dysfunction
in ME/CFS disease mechanisms. Given the lack of diagnostic molecular markers for ME/CFS and a very limited
understanding of its etiology, there is critical need to define new risk factors and mechanisms of ME/CFS
predisposition and severity. While early studies showed promise in identifying different metabolic, immunologic,
or microbial biomarkers of ME/CFS, these studies were limited in scope, sample size, or, importantly, integration
across datatypes, examining one or a small handful of correlates at a time. While this may be sufficient for
diseases with a more straightforward mechanism, ME/CFS' compound symptoms and potential etiologies require
integrated analysis that incorporates multiple datatypes. In addition, longitudinal and prospective studies are
needed to identify mechanisms of disease progression and severity. We hypothesize that immune
dysfunction is a central etiology of ME/CFS, both by virtue of its propensity to respond aberrantly to
environmental stimuli and its vulnerability to aberrant stimulation by the ME/CFS microbiome and/or its
metabolites. Our goal is to define likely clinical correlates of ME/CFS disease, centering on the microbiome and
metabolome as immune triggers. We will address multiple central goals of the Center, most notably the
application of computational modeling and machine learning approaches to integrate detailed clinical, immune,
metabolomic and microbiome datatypes to characterize and predict the immune responses triggered and the
associated clinical correlates. Moreover, this study will provide, in addition to valuable hypotheses to guide the
mechanistic work proposed in the Basic Research Project, a battery of different immune, metabolomic, and
microbial biomarkers associated with different ME/CFS subtypes and disease severity. This project benefits from
the deep clinical research expertise at Bateman Horne Center and University of Utah CTSA, cutting-edge core
services at The Jackson Laboratory, and the world-class computational and biostatistics team assembled here,
with expertise in clinical study design and integrative modeling of large-scale complex genomics cohorts. Our
Specific Aims are: 1) To assess immunological abnormalities and blood metabolomic changes prospectively in
a large ME/CFS patient cohort; 2) To define correlations between microbiome ecological distribution and clinical
state of ME/CFS; and 3) to establish ME/CFS clinical ontology with computational and biostatistical analysis of
the immune, metabolic and microbiome interactome in ME/CFS patients. Impact: Success of our aims will yield
a large-scale data repository and integrated analytic workflow that can accommodate samples from multiple
centers. Identified correlates will be strong...

## Key facts

- **NIH application ID:** 10248307
- **Project number:** 5U54NS105539-05
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Peter Nicholas Robinson
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $658,832
- **Award type:** 5
- **Project period:** 2017-09-30 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248307

## Citation

> US National Institutes of Health, RePORTER application 10248307, Topological Mapping of Immune, Microbiota, Metabolomic and Clinical Phenotypes to Reveal ME/CFS Disease Mechanisms - Clinical Research Project (5U54NS105539-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10248307. Licensed CC0.

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