What question did this study set out to answer?

To systematically characterize the activity of gene expression regulators across molecular subsets of systemic sclerosis and evaluate their association with severe clinical outcomes.

July 28, 2020JCI InsightOpen Access

Regulator combinations identify systemic sclerosis patients with more severe disease

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To systematically characterize the activity of gene expression regulators across molecular subsets of systemic sclerosis and evaluate their association with severe clinical outcomes.
Developed a computational framework to calculate regulator activity scores across four intrinsic systemic sclerosis molecular subsets (inflammatory, fibroproliferative, limited, and normal-like).
Correlated regulator activity scores with clinical parameters, including modified Rodnan skin score (MRSS) and the presence of interstitial lung disease (ILD).
Validated clinical associations in an independent longitudinal cohort monitored over 36–54 months to evaluate forced vital capacity (FVC) decline.
Regulator activity scores recapitulated the four intrinsic molecular subsets, with subset-specific regulators correlating with modified Rodnan skin score severity.
Patients within fibroproliferative and inflammatory subsets exhibited more severe pathophenotypes, including higher skin scores and increased risk of interstitial lung disease.
An independent validation cohort demonstrated that the group with more severe interstitial lung disease experienced accelerated forced vital capacity decline over 36–54 months.

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Implication

Cohort analysis reveals that gene expression regulator profiles stratify disease severity and lung decline in systemic sclerosis, highlighting targets for personalized risk assessment.

Cite This Study

Wang et al. (2020) studied this question.

synapsesocial.com/papers/6a7de5763fa445558d7d8bbe https://doi.org/10.1172/jci.insight.137567

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Implication

Cohort analysis reveals that gene expression regulator profiles stratify disease severity and lung decline in systemic sclerosis, highlighting targets for personalized risk assessment.

Regulator combinations identify systemic sclerosis patients with more severe disease

Key Points

Discussion

Implication

Cite This Study

Regulator combinations identify systemic sclerosis patients with more severe disease

Key Points

Discussion

Implication

Cite This Study

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