title: Longitudinal monitoring of gene expression in ultra-low-volume blood samples self-collected at home.
abstract: Blood transcriptional profiles could serve as biomarkers of clinical changes in subjects at-risk for or diagnosed with diabetes. However, transcriptional variation over time is poorly understood due to the impracticality of frequent longitudinal phlebotomy in large patient cohorts. We have developed a novel transcriptome assessment method that could be applied to fingerstick blood samples self-collected by study volunteers. Fifteen μL of blood from a fingerstick yielded sufficient RNA to analyse > 176 transcripts by high-throughput quantitative polymerase chain reaction (PCR). We enrolled 13 subjects with type 1 diabetes and 14 controls to perform weekly collections at home for a period of 6 months. Subjects returned an average of 24 of 26 total weekly samples, and transcript data were obtained successfully for > 99% of samples returned. A high degree of correlation between fingerstick data and data from a standard 3 mL venipuncture sample was observed. Increases in interferon-stimulated gene expression were associated with self-reported respiratory infections, indicating that real-world transcriptional changes can be detected using this assay. In summary, we show that longitudinal monitoring of gene expression is feasible using ultra-low-volume blood samples self-collected by study participants at home, and can be used to monitor changes in gene expression frequently over extended periods.
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Speake
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Whalen
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: V H
authors.initials: VH
authors.lastname: Gersuk
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chaussabel
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Odegard
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Greenbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001800:Blood Specimen Collection; D001810:Blood Volume; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018962:Phlebotomy; D012313:RNA / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D012648:Self Care; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012313:RNA
keywords: autoimmunity; diabetes; transcriptomics