Bias in High-Throughput Analysis of miRNAs and Implications for Biomarker Studies

A certain degree of bias in high-throughput molecular technologies including microarrays and next-generation sequencing (NGS) is known. To quantify the actual impact of the biomarker discovery platform on miRNA profiles, we first performed a meta-analysis: raw data of 1 539 microarrays and 705 NGS b...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2016-02, Vol.88 (4), p.2088-2095
Main Authors: Backes, Christina, Sedaghat-Hamedani, Farbod, Frese, Karen, Hart, Martin, Ludwig, Nicole, Meder, Benjamin, Meese, Eckart, Keller, Andreas
Format: Article
Language:English
Subjects:
Analytical chemistry
Arrays
Bias
Biomarkers
Biomarkers - analysis
Correlation analysis
Counting
High-Throughput Nucleotide Sequencing
Humans
Mathematical analysis
MicroRNAs - analysis
MicroRNAs - genetics
Nucleotides
Oligonucleotide Array Sequence Analysis
Platforms
Polymerase chain reaction
Real-Time Polymerase Chain Reaction
Ribonucleic acid
Ribonucleic acids
RNA
Sequence Analysis, RNA
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Summary:A certain degree of bias in high-throughput molecular technologies including microarrays and next-generation sequencing (NGS) is known. To quantify the actual impact of the biomarker discovery platform on miRNA profiles, we first performed a meta-analysis: raw data of 1 539 microarrays and 705 NGS blood-borne miRNomes were statistically evaluated, suggesting a substantial influence of the technology on biomarker profiles. We observed highly significant dependency of the miRNA nucleotide composition on the expression level. Higher expression in NGS was discovered for uracil-rich miRNAs (p = 7 × 10–37), while high expression in microarrays was found predominantly for guanine-rich miRNAs (p = 3 × 10–33). To verify the findings, 10 identical replicates of one individual were measured using NGS and microarrays (2 525 miRNAs from miRBase version 21). Overall, we calculated a correlation coefficient of 0.414 for both technologies. Detailed analysis however revealed that the correlation was observed only for miRNAs in the early miRBase versions (
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.5b03376