ArticleNucleic acids research2016
Toward reliable biomarker signatures in the age of liquid biopsies - how to standardize the small RNA-Seq workflow.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Systematic Review of the Diagnostic and Clinical Utility of Salivary microRNAs in Traumatic Brain Injury (TBI).International journal of molecular sciences · 2022Pooled it
- Pooled it
- Quantification of EV-associated miRNA in liquid biopsies for biomarker signature development.Extracellular vesicles and circulating nucleic acids · 2026Review
- How Laboratory Guidelines Promote the Validity of Circulating Extracellular Vesicle-Associated Nucleic Acid Biomarker Signatures in Liquid Biopsy.International journal of molecular sciences · 2025Review
- Standardization of preclinical methodologies for discovery and validation of circulating microRNA biomarkers for post-traumatic epileptogenesis - Lessons learned from the EpiBioS4Rx Project 1.Epilepsy research · 2025Article
- Technical considerations and review of urinary microRNAs as biomarkers for chronic kidney disease in dogs and cats.Veterinary clinical pathology · 2025Review
- A promising frontier of circulating messenger RNA in liquid biopsy: From mechanisms to clinical applications.International journal of cancer · 2025Review
- Article
- Circulating microRNAs in Body Fluid: "Fingerprint" RNA Snippets Deeply Impact Reproductive Biology.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- MicroRNAs: circulating biomarkers for the early detection of imperceptible cancers via biosensor and machine-learning advances.Oncogene · 2024Review
- Preanalytical, analytical and postanalytical considerations in circulating microRNAs measurement.Biochemia medica · 2024Review
- Microbiota of Saliva: A Non-invasive Diagnostic Tool.Indian journal of microbiology · 2024Review
- New prospects of environmental RNA metabarcoding research in biological diversity, ecotoxicological monitoring, and detection of COVID-19: a critical review.Environmental science and pollution research international · 2024Review
- Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues.Nature biotechnology · 2024Article
- Effects of Cow's Milk Processing on MicroRNA Levels.Foods (Basel, Switzerland) · 2023Article
- Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer.International journal of molecular sciences · 2023Review
- Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis.Scientific reports · 2023Article
- Variant biomarker discovery using mass spectrometry-based proteogenomics.Frontiers in aging · 2023Review
- The potential key genes and pathways associated with Wilms tumor in quest of proper candidates for diagnostic and therapeutic purposes.Scientific reports · 2022Review
- Variation of miRNA Content in Cow Raw Milk Depending on the Dairy Production System.International journal of molecular sciences · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small RNA-Seq has emerged as a powerful tool in transcriptomics, gene expression profiling and biomarker discovery. Sequencing cell-free nucleic acids, particularly microRNA (miRNA), from liquid biopsies additionally provides exciting possibilities for molecular diagnostics, and might help establish disease-specific biomarker signatures. The complexity of the small RNA-Seq workflow, however, bears challenges and biases that researchers need to be aware of in order to generate high-quality data. Rigorous standardization and extensive validation are required to guarantee reliability, reproducibility and comparability of research findings. Hypotheses based on flawed experimental conditions can be inconsistent and even misleading. Comparable to the well-established MIQE guidelines for qPCR experiments, this work aims at establishing guidelines for experimental design and pre-analytical sample processing, standardization of library preparation and sequencing reactions, as well as facilitating data analysis. We highlight bottlenecks in small RNA-Seq experiments, point out the importance of stringent quality control and validation, and provide a primer for differential expression analysis and biomarker discovery. Following our recommendations will encourage better sequencing practice, increase experimental transparency and lead to more reproducible small RNA-Seq results. This will ultimately enhance the validity of biomarker signatures, and allow reliable and robust clinical predictions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.