Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy
Julie Choi
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorZitian Tang
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorWendy Dong
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorJenna Ulibarri
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorElvisa Mehinovic
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorSimone Thomas
Department of Neurology, Neuromuscular Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorAhmet 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
Search for more papers by this authorCorresponding 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])
Search for more papers by this authorJulie Choi
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorZitian Tang
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorWendy Dong
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorJenna Ulibarri
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorElvisa Mehinovic
Department of Genetics, School of Medicine, Washington University, St. Louis, Missouri, USA
Search for more papers by this authorSimone Thomas
Department of Neurology, Neuromuscular Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorAhmet 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
Search for more papers by this authorCorresponding 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])
Search for more papers by this authorFunding: 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.
Open Research
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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