Dataset Information

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.

ABSTRACT: Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18-25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual's exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals.

SUBMITTER: Yeri A

PROVIDER: S-EPMC5356006 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.

Yeri Ashish A Courtright Amanda A Reiman Rebecca R Carlson Elizabeth E Beecroft Taylor T Janss Alex A Siniard Ashley A Richholt Ryan R Balak Chris C Rozowsky Joel J Kitchen Robert R Hutchins Elizabeth E Winarta Joseph J McCoy Roger R Anastasi Matthew M Kim Seungchan S Huentelman Matthew M Van Keuren-Jensen Kendall K

Scientific reports 20170317

Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18-25 years. Many participants provided more than one sample, allowing us to investigate variability ...[more]

PMID: 28303895

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Project description:Extracellular vesicles such as exosomes are selectively enriched in RNA that has potential for use as disease biomarkers. To systemically characterize circulating extracellular RNA profiles, we performed RNA sequencing analysis on plasma extracellular vesicles derived from 192 individuals including 100 colon cancer, 36 prostate cancer and 6 pancreatic cancer patients along with 50 healthy individuals. Of ~12.6 million raw reads for each of these subjects, the number of mappable reads aligned to RNA references was ~5.4 million including microRNAs(miRNAs) (~40.4%), piwi-interacting RNAs(piwiRNAs) (~40.0%), pseudo-genes (~3.7%), long noncoding RNAs (lncRNAs) (~2.4%), tRNAs (~2.1%), and mRNAs (~2.1%). To select the best candidates for potential extracellular RNA reference controls, we performed abundant level stability testing and identified a set of miRNAs showing relatively consistent expression. To estimate biological variations, we performed association analysis of expression levels with age and sex in healthy individuals. This analysis showed significant sex association with seven small noncoding RNAs (false discovery rate, or FDR<0.05), while no small noncoding RNAs were statistically associated with age. To identify disease-associated RNA transcripts, we performed analysis of covariance by including disease status, age, sex, RNA isolation and gel size selection dates. We observed a gradual increase of significantly associated RNAs (in particular, miRNAs) with disease advancement as denoted by cancer staging. We found significant association of miR-125a-5p and miR-1246-3p with all cancer types tested (FDR<0.05). Based on the disease associations, we developed cancer type-specific multivariate statistical models to predict disease status with an area under the ROC curve from 0.67 in stage I colon cancer to 0.92 in advanced prostate cancer. To date, this is the largest RNA-seq study to systematically profile extracellular RNA species, which has not only provided a baseline reference profile for circulating extracellular RNA, but also a set of RNA candidates for reference controls and disease biomarkers.

Dataset Information

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.

Publications

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.

Similar Datasets

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