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Principal Investigator: Xuanhong Cheng
Organization: LEHIGH UNIVERSITY
Fiscal Year: 2024
Award: $390,178
Funding agency: National Institute of Neurological Disorders and Stroke
Transcriptional profiling of proliferative skeletal muscle mononucleated cells coupled with broadband
electrical cytometry towards diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome
PROJECT SUMMARY / ABSTRACT
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, acquired disease affecting up
to 2.5 million Americans. With increasing evidence that a proportion of patients with COVID-19 experience
prolonged convalescence and chronic symptoms similar to ME/CFS, it is suggested that the incidence of
ME/CFS will increase significantly. Currently, no single biomarkers or pathognomonic signs have been identified
for diagnostic measures. Instead, diagnosis is based on clinical symptoms after exclusion of other possible
etiologies known to cause fatigue, a method that does not prescribe adequate sensitivity or specificity. Since
clinical symptoms suggest that skeletal muscle is a major and consistent target of the pathology, and proliferative
skeletal mononucleated cells (SMMCs) are excellent indicators of muscle disorders, we hypothesize that
proliferative SMMCs from of ME/CFS patients are distinguishable from those of healthy individuals on the
molecular and cellular level. Proposed work will investigate gene expression, functional pathways and electrical
characteristics of single SMMCs from ME/CFS and healthy donors to identify a matrix of molecular and
biophysical markers to enable future development of diagnostics. Single-cell mRNA profiling will identify
differential gene expression describing alterations that occur in ME/CFS samples. Using differential biomarkers
identified by scRNA-seq, subpopulations of SMMCs unique to ME/CFS will be sorted to study changes in protein
expression and cell function. Furthermore, an impedance cytometer recently developed by our team will be used
to measure single cell electrical spectra, and disease-specific signatures will be identified by machine learning.
The molecular, cellular and electrical characteristics will be further correlated with each other to provide a
comprehensive understanding of the SMMC pathology in ME/CFS, an untapped subject. The proposed single-
cell transcriptome analysis of SMMCs from ME/CFS patients represents the first study of its kind and will greatly
contribute to the fundamental knowledge of the role of proliferative SMMCs in ME/CFS dysfunctions. Compared
to molecular approaches, proposed impedance cytometry captures a ‘big picture’ of the multitude of changes
contributing to abnormalities in ME/CFS SMMCs. As specific molecular markers have not been identified for
diagnostic measures, the holistic electrical characteristics of single cells offer a unique perspective of global
changes in SMMCs and hold great diagnostic potential in the future. Integration of electrical and biological studies
of SMMCs will further allow interpretation of the impedance spectra to promote sensing specificity.
Terms: <21+ years old><Adult><Adult Human><Affect><American><Biological><Biological Markers><Biophysics><Biopsy Sample><Biopsy Specimen><Biosensing Technics><Biosensing Techniques><Blood leukocyte><COVID crisis><COVID epidemic><COVID infected patient><COVID pandemic><COVID patient><COVID positive patient><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infected patient><COVID-19 pandemic><COVID-19 patient><COVID-19 period><COVID-19 positive patient><COVID-19 public health crisis><COVID-19 years><COVID19 patient><COVID19 positive patient><Causality><Cell Body><Cell Function><Cell Isolation><Cell Physiology><Cell Process><Cell Segregation><Cell Separation><Cell Separation Technology><Cells><Cellular Function><Cellular Physiology><Cellular Process><Characteristics><Chronic Fatigue Disorder><Chronic Fatigue Syndrome><Chronic Fatigue and Immune Dysfunction Syndrome><Chronic Infectious Mononucleosis-Like Syndrome><Clinical><Complex><Convalescence><Coupled><Coupling><Cytometry><Development><Diagnosis><Diagnostic><Differential Gene Expression><Disease><Disorder><Dysfunction><Electrical Impedance><Etiology><Evaluation><Exclusion><Exertion><Expression Signature><Fatigue><Functional disorder><Future><Gene Expression><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profile><Gene Expression Profiling><Gene Transcription><Genetic><Genetic Markers><Genetic Transcription><Global Change><Heterogeneity><Impairment><Impedance><Incidence><Individual><Intracellular Structure><Investigation><Knowledge><Lack of Energy><Leukocytes><Leukocytes Reticuloendothelial System><Life><ME/CFS><Machine Learning><Marrow leukocyte><Measures><Messenger RNA><Methods><Molecular><Molecular Analysis><Muscle><Muscle Disease><Muscle Disorders><Muscle Tissue><Muscular Diseases><Myalgic Encephalomyelitis><Myopathic Conditions><Myopathic Diseases and Syndromes><Myopathic disease or syndrome><Myopathy><Non-Polyadenylated RNA><Organelles><Pathologic><Pathology><Pathway interactions><Patients><Physiology><Physiopathology><Postviral Fatigue Syndrome><Prevalence><Procedures><Qualifying><Quality Control><RNA><RNA Expression><RNA Gene Products><Research><Ribonucleic Acid><Role><Royal Free Disease><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infected patient><SARS-CoV-2 pandemic><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SCmRNAseq><Sampling><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Single cell mRNA seq><Skeletal Muscle><Sorting><Specificity><Subcellular Process><Subcellular structure><Symptoms><System><Techniques><Testing><Tissue-Specific Differential Gene Expression><Tissue-Specific Gene Expression><Transcript Expression Analyses><Transcript Expression Analysis><Transcription><Voluntary Muscle><White Blood Cells><White Cell><Work><adulthood><analyze gene expression><bio-markers><biologic><biologic marker><biomarker><biomarker identification><biophysical approaches><biophysical foundation><biophysical methodology><biophysical methods><biophysical principles><biophysical sciences><biophysical techniques><biosensing><causation><cell sorting><cell type><chronic symptom><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infected patient><coronavirus disease 2019 pandemic><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease 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disorder><pathophysiology><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><persistent symptom><programs><protein expression><scRNA-seq><sensor><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell mRNA sequencing><single cell technology><single cell transcriptomic profiling><single-cell RNA sequencing><skeletal><social role><transcriptional profile><transcriptional profiling><transcriptional signature><transcriptome><white blood cell><white blood corpuscle>