Volume 12, Issue 4 pp. 674-685
REVIEW
Open Access

Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy

Julie Choi

Julie Choi

Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA

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Zitian Tang

Zitian Tang

Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA

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Wendy Dong

Wendy Dong

Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA

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Jenna Ulibarri

Jenna Ulibarri

Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA

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Elvisa Mehinovic

Elvisa Mehinovic

Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA

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Simone Thomas

Simone Thomas

Department of Neurology, Neuromuscular Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Ahmet Höke

Ahmet Höke

Department of Neurology, Neuromuscular Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Sheng Chih Jin

Corresponding Author

Sheng Chih Jin

Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA

Department of Pediatrics, School of Medicine, Washington University, St. Louis, Missouri, USA

Correspondence:

Sheng Chih Jin ([email protected])

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First published: 24 March 2025

Funding: J.C. and W.D. are supported by Washington University's Genome Analysis Training Program (T32HG000045). J.U. is supported by Washington University's Cellular and Molecular Biology Umbrella Training Program (T32GM007067) and the Maximizing Student Diversity program (R25GM103757). S.C.J. is supported by the Hydrocephalus Association Innovator Award, Cerebral Palsy Alliance Research Foundation Project Grant (PRG03121), WashU Children's Discovery Institute Faculty Scholar Award (CDI-FR-2021-926), and NIH U19NS130607, R01NS111029, and R01NS131610. A.H. is supported by NIH (R21NS135481, P30 MH075673-011), Wellcome Trust, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Merkin Peripheral Neuropathy and Nerve Regeneration Center.

Julie Choi and Zitian Tang contributed equally to this work.

ABSTRACT

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants associated with PN. However, the establishment and application of next-generation sequencing (NGS) and, more recently, long-read/single-cell sequencing have revolutionized the field, accelerating the discovery of novel disease-causing variants and challenging previous assumptions about pathogenicity. This review traces the evolution of genomic technologies in PN research, emphasizing the pivotal role of NGS in uncovering genetic complexities. We provide a comprehensive analysis of established genomic approaches such as genome-wide association studies, targeted gene panel sequencing, and whole-exome/genome sequencing, alongside emerging multiomic technologies including RNA sequencing and proteomics. Integrating these approaches promises holistic insights into PN pathophysiology, potentially revealing new biomarkers and therapeutic targets. Furthermore, we discuss the clinical implications of genomic and multiomic integration, highlighting their potential to enhance diagnostic accuracy, prognostic assessment, and personalized treatment strategies for PN. Challenges and questions in standardizing these technologies for clinical use are raised, underscoring the need for robust guidelines to maximize their clinical utility.

Conflicts of Interest

The authors report no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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