Integrative exome sequencing and machine learning identify MICB and interferon pathway genes as contributors to SSc risk.

Journal: Annals of the rheumatic diseases
Published Date: Aug 1, 2025

Abstract

OBJECTIVES: Systemic sclerosis (SSc) is a complex autoimmune disease with both known and unidentified genetic contributors. While genome-wide association studies (GWAS) have implicated multiple loci, many reside in noncoding regions. We aimed to identify novel protein-coding variants and pathogenic pathways using exome sequencing (ES) integrated with an Evolutionary Action-Machine Learning (EAML) framework, single-cell RNA sequencing (scRNA-seq), and expression quantitative trait locus (eQTL) analysis.

Authors

  • Shamika Ketkar
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Hongzheng Dai
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Lindsay Burrage
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • David Murdock
    Department of Internal Medicine, McGovern Medical School, University of Texas, Houston, TX, USA.
  • Brian Dawson
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Marialbert Acosta-Herrera
    Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
  • Martin Kerick
    Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
  • Javier Martin
    Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
  • Kevin Wilhelm
    Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX, USA.
  • Jennifer Kay Asmussen
    Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX, USA.
  • Olivier Lichtarge
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Regeneron Genetics Center
    Geisinger Medical Center, Danville, PA, USA.
  • Shervin Assassi
    Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine UTHealth Houston TX 77030 USA.
  • Maureen D Mayes
    Rheumatology and Clinical Immunogenetics, The University of Texas Health Science Center Houston Medical School, Houston, Texas, USA.
  • Brendan H Lee
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: blee@bcm.edu.

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