A clinically validated human capillary blood transcriptome test for global systems biology studies

Abstract

To prevent and treat chronic diseases, including cancer, a global application of systems biology is needed. We report here a whole blood transcriptome test that needs only 50 μl of capillary (fingerprick) blood. This test is suitable for global applications because the samples are preserved at ambient temperature for up to 4 weeks and the RNA preservative inactivates all pathogens, enabling safe transportation. Both the laboratory and bioinformatic steps are automated and performed in a clinical lab, which minimizes batch effects and creates unbiased datasets. Given its clinical testing performance and accessibility to traditionally underrepresented and diverse populations, this test offers a unique ability to reveal molecular mechanisms of disease and enable longitudinal, population-scale studies.

At-home blood collection and stabilization in high temperature climates using homeRNA

“…To test the ability of the RNA preservative solution to preserve blood transcriptome, Toma et al collected blood samples from participants ( n = 3) and stored at ambient temperature (22°C) or −80°C for 0, 7, 14, and 28 days, with and without shipping. They found high correlation coefficients between gene expression levels from the samples in all conditions, demonstrating the efficacy of the RNA stabilization solution to preserve RNA integrity over 28 days ( 8 ).…”

“…Logistically, relying on phlebotomy for collection geographically confines blood collections to clinic/lab locations or research institutes. Several self-blood collection technologies have been developed for remote use, including fingersticks ( 8 ), dried blood spots ( 14 – 16 ), and lancet-based technologies that collect blood from the upper arm ( 17 – 21 ), such as the Tasso-SST™ device that we use in our home-sampling and RNA stabilization kits (including the work in this manuscript). Another major challenge of remote blood transcriptomics is stabilization of whole blood RNA to minimize RNA degradation due to spontaneous degradation via autohydrolysis or degradation due to the presence of ribonucleases ( 22 ).…”

“…Another major challenge of remote blood transcriptomics is stabilization of whole blood RNA to minimize RNA degradation due to spontaneous degradation via autohydrolysis or degradation due to the presence of ribonucleases ( 22 ). Toma et al developed an at-home blood collection kit that collects 50 µl of capillary blood via fingerstick and mixes with a proprietary RNA preservative solution at a 1:4 ratio ( 8 ). To test the ability of the RNA preservative solution to preserve blood transcriptome, Toma et al collected blood samples from participants ( n = 3) and stored at ambient temperature (22°C) or −80°C for 0, 7, 14, and 28 days, with and without shipping.…”

“…Consequently, whole blood RNA transcript analysis has emerged as an avenue for realizing the goals of personalized medicine (2,3). Key biomarkers discovered through blood transcriptomic studies have potential applications in novel therapeutics and diagnostics (4)(5)(6)(7)(8) and have provided new avenues for disease monitoring of chronic (9,10), autoimmune (11,12), and infectious diseases (13). By combining home-sampling technologies and transcriptomics, one can further expand upon these applications, opening up both biomarker discovery through discovery-based research studies, and bring applications such as gene expression-based disease monitoring and diagnostics to home-based tests.…”

Single cell profiling of capillary blood enables out of clinic human immunity studies

“…Additionally, capillary blood is being shown to be comparable to traditional venous blood draws for a variety of applications. For example, Catala et al have shown that 39 out of 45 clinically relevant metabolites had overlapping ranges between capillary blood vs traditional venous blood draws 13 , and Toma et al have shown strong correlation (Spearman correlation coefficient ≥ 0.95) between bulk RNA sequencing data between capillary and venous blood from the same donor 14 . However, to date, scRNA-seq of human capillary blood has not yet been validated nor applied to study the immune system.…”