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Series GSE127208 Query DataSets for GSE127208
Status Public on Feb 27, 2019
Title Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs
Organism Homo sapiens
Experiment type Expression profiling by array
Summary We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful withinsubject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis.
 
Overall design First, we used a powerful longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low pain and high pain states. Second, we prioritized the list of candidate biomarkers with a Bayesian-like Convergent Functional Genomics approach, comprehensively integrating previous published human and animal model evidence in the field for involvement in pain, and directly citing it. Third, we validated our top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with a clinical diagnosis of a pain disorder and with high scores on pain severity and functional impact ratings. Fourth, we tested if the candidate biomarkers from the first three steps are able to predict high pain state, and future emergency department (ED) visits for pain, in another independent cohort of psychiatric subjects. We tested the biomarkers in all subjects in the independent test cohort, as well as in a more personalized fashion by gender and psychiatric diagnosis, showing increased accuracy with the personalized approach. Fifth, we assessed if our biomarkers have evidence for involvement in other psychiatric and related disorders, as well as analyzed the biological pathways and networks they are involved in. Sixth, we bioinformatically identified which of our individual biomarkers are modulated by existing drugs and thus can be used for pharmacogenomic population stratification and measuring of response to treatment, as well as used the gene expression signatures of the top predictive biomarkers to interrogate the Connectivity Map database from Broad/MIT to identify drugs and natural compounds that could be repurposed for treating pain.
 
Contributor(s) Niculescu AB, Le-Niculescu H
Citation(s) 30755720
Submission date Feb 26, 2019
Last update date Feb 28, 2019
Contact name Dr. Alexander B. Niculescu
E-mail anicules@iupui.edu
Phone 317-274-6544
Organization name Indiana University Medical School
Department Psychiatry
Lab Neuroscience Building Room 203
Street address 320 W. 15th Street
City Indianapolis
State/province IN
ZIP/Postal code 46202
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (674)
GSM3630000 Participant ID and visit (v) number [phchp004v2]
GSM3630001 Participant ID and visit (v) number [phchp004v3]
GSM3630002 Participant ID and visit (v) number [phchp004v4]
Relations
BioProject PRJNA524343

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE127208_DiscoveryCohortMatrix_Mas5_ABS_call_data.txt.gz 633.7 Kb (ftp)(http) TXT
GSE127208_RAW.tar 3.2 Gb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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