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Series GSE149314 Query DataSets for GSE149314
Status Public on Apr 25, 2020
Title Patient genetics is linked to chronic wound microbiome composition and healing
Organism Homo sapiens
Experiment type Genome variation profiling by array
Summary The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
Overall design An observational two-cohort microbiome genome wide association study (GWAS) was conducted to first identify candidate SNPs which may influence wound microbiome diversity (n = 79 post QC) [Cohort 1 samples in this series]. An experimental followup GWAS (n = 85) was conducted using only the previously suggested SNPs [Cohort 2 samples in this series]. Patients were considered for study if their wound infections had received 16s-based amplicon microbial profiling at their baseline infection, and baseline microbial measurements were then assessed against patient outcomes for individuals whom we had healing outcome data for (n = 58).
Contributor(s) Tipton C, Phillips C
Citation(s) 32555671
Submission date Apr 24, 2020
Last update date Jul 27, 2020
Contact name Caleb Phillips
Phone 8068348181
Organization name Texas Tech University
Department Department of Biological Sciences
Lab Phillips Lab
Street address 2901 Main Ave.
City Lubbock
State/province Texas
ZIP/Postal code 79409
Country USA
Platforms (1)
GPL23391 Infinium Global Screening Array
Samples (170)
GSM4497137 81
GSM4497138 1145
GSM4497139 1179
BioProject PRJNA627947

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
GSE149314_RAW.tar 72.1 Mb (http)(custom) TAR
GSE149314_TX_micro.bed.gz 6.5 Mb (ftp)(http) BED
GSE149314_TX_micro.bim.gz 8.1 Mb (ftp)(http) BIM
GSE149314_TX_micro.fam.gz 476 b (ftp)(http) FAM
GSE149314_cov2.txt.gz 5.2 Kb (ftp)(http) TXT
GSE149314_p2_cov2.txt.gz 5.3 Kb (ftp)(http) TXT
GSE149314_pheno_final.txt.gz 1.1 Kb (ftp)(http) TXT
GSE149314_pheno_p2.txt.gz 1.1 Kb (ftp)(http) TXT
GSE149314_ttgwas_p2.bed.gz 6.6 Mb (ftp)(http) BED
GSE149314_ttgwas_p2.bim.gz 8.0 Mb (ftp)(http) BIM
GSE149314_ttgwas_p2.fam.gz 474 b (ftp)(http) FAM
GSE149314_update_ids.txt.gz 558 b (ftp)(http) TXT
GSE149314_update_p2_ids_clean.txt.gz 877 b (ftp)(http) TXT
Processed data are available on Series record

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