Prioritizing and selecting likely novel miRNAs from NGS data

Backes, Christina; Meder, Benjamin; Hart, Martin; Ludwig, Nicole; Leidinger, Petra; Vogel, Britta; Galata, Valentina; Roth, Patrick; Menegatti, Jennifer; Grässer, Friedrich A.; Ruprecht, Klemens; Kahraman, Mustafa; Grossmann, Thomas; Haas, Jan; Meese, Eckart; Keller, Andreas

doi:10.1093/nar/gkv1335

Cited by 53 publications

(59 citation statements)

References 23 publications

(29 reference statements)

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“…miRNAs were quantified similar to the popular miRDeep2 [19] algorithm. The prediction of novel miRNAs was performed using an extended feature set built up on novoMiRank [12]. For classification, an AdaBoost model using decision trees was applied.…”

Section: Methodsmentioning

confidence: 99%

“…We first evaluated the reproducibility of sequencing on standardized brain and heart samples, then compared the performance to Agilent’s microarray technique and finally evaluated blood samples. Using the web-based miRNA analysis pipeline miRmaster and the tool novoMiRank [12], we finally predicted 135 new high-likely miRNA candidates specific for tissue and 35 new miRNA candidates specific for blood samples.…”

Section: Introductionmentioning

confidence: 99%

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cPAS-based sequencing on the BGISEQ-500 to explore small non-coding RNAs

et al. 2016

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BackgroundWe present the first sequencing data using the combinatorial probe-anchor synthesis (cPAS)-based BGISEQ-500 sequencer. Applying cPAS, we investigated the repertoire of human small non-coding RNAs and compared it to other techniques.ResultsStarting with repeated measurements of different specimens including solid tissues (brain and heart) and blood, we generated a median of 30.1 million reads per sample. 24.1 million mapped to the human genome and 23.3 million to the miRBase. Among six technical replicates of brain samples, we observed a median correlation of 0.98. Comparing BGISEQ-500 to HiSeq, we calculated a correlation of 0.75. The comparability to microarrays was similar for both BGISEQ-500 and HiSeq with the first one showing a correlation of 0.58 and the latter one correlation of 0.6. As for a potential bias in the detected expression distribution in blood cells, 98.6% of HiSeq reads versus 93.1% of BGISEQ-500 reads match to the 10 miRNAs with highest read count. After using miRDeep2 and employing stringent selection criteria for predicting new miRNAs, we detected 74 high-likely candidates in the cPAS sequencing reads prevalent in solid tissues and 36 candidates prevalent in blood.ConclusionsWhile there is apparently no ideal platform for all challenges of miRNome analyses, cPAS shows high technical reproducibility and supplements the hitherto available platforms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0287-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

cPAS-based sequencing on the BGISEQ-500 to explore small non-coding RNAs

et al. 2016

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“…However, technical and bioinformatics issues may have increased the number of predicted miRNAs, likely beyond the number of true miRNAs [81]. Thus, improved computational approaches [82] with in-depth validation are required to find true new miRNAs. The abovementioned issues, in combination with complex experimental workflows and long turn-around times limit the application of microarrays and high-throughput sequencing in clinical routine diagnosis.…”

Section: New Measurement Devicesmentioning

confidence: 99%

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

2016

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Significant effort has been devoted to discovering microRNA (miRNA) disease biomarkers. In particular, miRNAs in whole blood or specific blood components are candidates for improving the diagnosis of diseases, including life-threatening pathologies. This review covers the challenges crucial for the translation of miRNAs in body fluids (circulating miRNAs) from a research setting into a clinical care scenario. First, we discuss the specificity of miRNA biomarkers for the diagnosis of a disease. While single miRNAs such as miR-20a, miR-21, miR-155, and miR-126 are frequently not disease specific, miRNA signatures that consist of a plurality of different miRNAs may help to improve differentiation between pathologies. Second, we discuss the degree of reproducibility and highlight selected validation studies. While single miRNA markers are often confirmed by independent studies, miRNA signatures are less frequently verified. Third, we address challenges to the profiling of miRNAs in high-throughput settings and we discuss the appropriateness of various analytical platforms and bioinformatics towards a clinical application of miRNAs. Finally, we shed light on the suitability of enriched miRNA sources, e.g. fractionation of body fluids for extracellular vesicles such as exosomes or blood cells, to develop miRNA signatures. With an increasing number of verified miRNA signatures and with the advance of matured medium-throughput approaches in clinical settings, specific miRNA markers are increasingly likely to contribute to human healthcare.

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“…Project such as the Encyclopedia of DNA Elements project (ENCODE), which aims to map all functional elements in the human genome, has made great progress . Methods of RNA microarray and novel high‐throughput technologies such as next‐generation sequencing (NGS) provide powerful tools for the analysis of miRNA transcription profiles and their target genes in diseases . miRNAs regulate target genes through the base pair interaction of seed region (nucleotide 2‐7 of the miRNA) with target mRNA 3′UTR.…”

Section: Perspective Of Mirna Therapiesmentioning

confidence: 99%

Dysregulation of miRNA and its potential therapeutic application in schizophrenia

Cao

Zhen

2018

CNS Neurosci Ther

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Although it is generally believed that genetic and developmental factors play critical roles in pathogenesis of schizophrenia, however, the precise etiological mechanism of schizophrenia remains largely unknown. Over past decades, miRNAs have emerged as an essential post-transcriptional regulator in gene expression regulation. The importance of miRNA in brain development and neuroplasticity has been well-established. Abnormal expression and dysfunction of miRNAs are known to involve in the pathophysiology of many neuropsychiatric diseases including schizophrenia. In this review, we summarized the recent findings in the schizophrenia-associated dysregulation of miRNA and functional roles in the development and pathogenesis of schizophrenia. We also discussed the potential therapeutic implications of miRNA regulation in the illness.

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Prioritizing and selecting likely novel miRNAs from NGS data

Cited by 53 publications

References 23 publications

cPAS-based sequencing on the BGISEQ-500 to explore small non-coding RNAs

cPAS-based sequencing on the BGISEQ-500 to explore small non-coding RNAs

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

Dysregulation of miRNA and its potential therapeutic application in schizophrenia

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