Evaluation of noninvasive biospecimens for transcriptome studies

Abstract

Transcriptomic studies lend insight into the biology of genetic regulation and bear promise in furthering the goals of precision medicine. However, the cost of RNA-sequencing and types of tissues currently assayed pose major limitations to study expansion and disease-relevant discovery. Here, we develop methods for sampling noninvasive biospecimens for transcriptome studies, investigate their technical and biological characteristics, and assess the feasibility of using noninvasive samples in transcriptomic and clinical applications. Of the four tissues we studied (buccal swabs, hair follicles, saliva, and urine cell pellets), we found hair follicles and urine cell pellets to be most promising due to the consistency of sample quality, underlying biology, and capture of disease-relevant signals. We anticipate future use of noninvasive sampling will facilitate discovery by increasing sample sizes in more diverse populations and in tissues with greater cell type diversity and biological relatedness to disease mechanisms. Moreover, the nature of noninvasive samples enables complex study designs with greater ability to capture context-dependent mechanisms of genetic regulation.

Integrative omics approaches to advance rare disease diagnostics

“…Martorella and colleagues investigated the performance of RNA-seq in four fully non-invasive CATs: buccal swabs, hair follicles, saliva and urine cell pellets. 87 Hair samples provided the highest detection rate of Mendelian disease genes (63%), followed by saliva (53%), urine (43%) and buccal swabs (33%). Analysis of non-invasive CATs holds great promise; however, a more in-depth assessment of the clinical utility of transcriptomics in these tissues in larger patient cohorts is still required.…”

“…They identified a high similarity of gene expression profiles to fibroblasts and provided a diagnosis to 4 patients (8%). Martorella and colleagues investigated the performance of RNA‐seq in four fully non‐invasive CATs: buccal swabs, hair follicles, saliva and urine cell pellets 87 . Hair samples provided the highest detection rate of Mendelian disease genes (63%), followed by saliva (53%), urine (43%) and buccal swabs (33%).…”