Abstract
BackgroundEmerging evidence has been experimentally confirmed the tissue-specific expression of circRNAs (circRNAs). Global identification of human tissue-specific circRNAs is crucial for the functionality study, which facilitates the discovery of circRNAs for potential diagnostic biomarkers.ResultsIn this study, circRNA back-splicing junctions were identified from 465 publicly available transcriptome sequencing samples. The number of reads aligned to these identified junctions was normalized with the read length and sequence depth for each sample. We generated 66 models representing enriched circRNAs among human tissue transcriptome through biclustering algorithm. The result provides thousands of newly identified human tissue-specific circRNAs.ConclusionsThis result suggests that expression of circRNAs is not prompted by random splicing error but serving molecular functional roles. We also identified circRNAs enriched within circulating system, which, along with identified tissue-specific circRNAs, can serve as potential diagnostic biomarkers.
Highlights
Emerging evidence has been experimentally confirmed the tissue-specific expression of circRNAs
From the result 66 bicluster models, we found a huge portion of circRNAs express only in the specific tissue type
This result suggests that expression of circRNAs is not prompted by random splicing error but serving molecular functional roles
Summary
Emerging evidence has been experimentally confirmed the tissue-specific expression of circRNAs (circRNAs). Global identification of human tissue-specific circRNAs is crucial for the functionality study, which facilitates the discovery of circRNAs for potential diagnostic biomarkers. The existence of human circRNAs has been discovered and proven with electron microscopy for more than 30 years [1], it was only until 2012 with the advance of high throughput sequencing technology the ubiquitous expression of circRNA in mammals was found and proven [2]. Emerging evidence indicates the tissue-specific circRNAs play crucial roles in post-transcriptional level. The existence of circRNA within transcriptome sequencing data can be detected through identification of reads spanning these junctions. In previous studies [4], threshold applied to identify certain junctions as circRNA was that at least two unique reads spanning a head-tail junction. To discover human tissue-specific circRNAs, we collected 465 human transcriptome sequencing runs and applied the established pipeline. Expression level of circRNAs was estimated using the normalized counts of
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