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Cited by 51Fibromyalgia and Chronic Fatigue Syndrome ResearchLong-Term Effects of COVID-19Gene expression and cancer classification

Identifying illness parameters in fatiguing syndromes using classical projection methods

Broderick, Gordon, Craddock, R Cameron, Whistler, Toni, Taylor, Renee, Klimas, Nancy, Unger, Elizabeth R·2006·Pharmacogenomics
DOI 10.2217/14622416.7.3.407
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Abstract

OBJECTIVES: To examine the potential of multivariate projection methods in identifying common patterns of change in clinical and gene expression data that capture the illness state of subjects with unexplained fatigue and nonfatigued control participants. METHODS: Data for 111 female subjects was examined. A total of 59 indicators, including multidimensional fatigue inventory (MFI), medical outcome Short Form 36 (SF-36), Centers for Disease Control and Prevention (CDC) symptom inventory and cognitive response described illness. Partial least squares (PLS) was used to construct two feature spaces: one describing the symptom space from gene expression in peripheral blood mononuclear cells (PBMC) and one based on 117 clinical variables. Multiplicative scatter correction followed by quantile normalization was applied for trend removal and range adjustment of microarray data. Microarray quality was assessed using mean Pearson correlation between samples. Benjamini-Hochberg multiple testing criteria served to identify significantly expressed probes. RESULTS: A single common trend in 59 symptom constructs isolates of nonfatigued subjects from the overall group. This segregation is supported by two co-regulation patterns representing 10% of the overall microarray variation. Of the 39 principal contributors, the 17 probes annotated related to basic cellular processes involved in cell signaling, ion transport and immune system function. The single most influential gene was sestrin 1 (SESN1), supporting recent evidence of oxidative stress involvement in chronic fatigue syndrome (CFS). Dominant variables in the clinical feature space described heart rate variability (HRV) during sleep. Potassium and free thyroxine (T4) also figure prominently. CONCLUSION: Combining multiple symptom, gene or clinical variables into composite features provides better discrimination of the illness state than even the most influential variable used alone. Although the exact mechanism is unclear, results suggest a common link between oxidative stress, immune system dysfunction and potassium imbalance in CFS patients leading to impaired sympatho-vagal balance strongly reflected in abnormal HRV.

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Authors
Broderick, G., Craddock, R. C., Whistler, T., Taylor, R., Klimas, N., & Unger, E. R.
Affiliations
  • Centers for Disease Control and Prevention (US)
  • University of Illinois at Chicago, Department of Occupational Therapy, Chicago, IL, 60612, USA
Corresponding author
Broderick, Gordon
ORCID
Venue
Pharmacogenomics
Publisher
Informa UK Limited
Published
2006-04
Volume
7
Issue
3
Pages
407-419
ISSN
  • 1462-2416 (ISSN-L)
  • 1744-8042
DOI
10.2217/14622416.7.3.407
OpenAlex
W2148088721
Cited by
51
References
31
Citations by year
2025: 1 · 2021: 1 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2012: 4
FWCI
3.82
Type
journal article
Language
en
Open access
closed
Locations
  • Pharmacogenomics (publishedVersion)
  • PubMed (publishedVersion)
  • NSUWorks (Nova Southeastern University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
chronic fatigue syndrome, unexplained fatigue, fatigue syndrome, partial least squares, gene expression, peripheral blood mononuclear cells, symptom profiles, oxidative stress, immune dysfunction, potassium imbalance, heart rate variability, sympathovagal balance, free thyroxine
MeSH terms
Sestrins, Adult, Cognition, Female, Gene Frequency, Heat-Shock Proteins, Humans, Immunity, Ion Channels, Monocytes, Potassium, Water-Electrolyte Imbalance, Signal Transduction, Fatigue Syndrome, Chronic, Gene Expression, Multivariate Analysis, Least-Squares Analysis, Oxidative Stress, Oligonucleotide Array Sequence Analysis, Principal Component Analysis

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