ArticlePloS one2016
Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed, 22 citations in OpenAlex.
- Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).Molecular neurobiology · 2019Trial
- Does Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Represent a Poly-Herpesvirus Post-Virus Infectious Disease?Viruses · 2025Review
- Mucosal Viruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Missing Piece of the Puzzle?International journal of molecular sciences · 2025Review
- Cross-study analyses of microbial abundance using generalized common factor methods.BMC bioinformatics · 2023Article
- A Case of Successful Treatment of Recurrent Urinary Tract Infection by Extended-Spectrum β-Lactamase ProducingMicrobial drug resistance (Larchmont, N.Y.) · 2023Article
- Next Generation Sequencing Approaches to Characterize the Respiratory Tract Virome.Microorganisms · 2022Review
- High Throughput Sequencing for the Detection and Characterization of RNA Viruses.Frontiers in microbiology · 2021Review
- Comparison of Nucleic Acid Extraction Methods for a Viral Metagenomics Analysis of Respiratory Viruses.Microorganisms · 2020Article
- Clinical metagenomics for infectious corneal ulcers: Rags to riches?The ocular surface · 2020Article
- Insights into the Microbiome of Breast Implants and Periprosthetic Tissue in Breast Implant-Associated Anaplastic Large Cell Lymphoma.Scientific reports · 2019Article
- Recentrifuge: Robust comparative analysis and contamination removal for metagenomics.PLoS computational biology · 2019Article
- Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow.BMC infectious diseases · 2018Article
- RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Article
- Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities.Current opinion in virologyReview
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease causing indefinite fatigue. ME/CFS has long been hypothesised to have an infectious cause; however, no specific infectious agent has been identified. We used metagenomics to analyse the RNA from plasma samples from 25 individuals with ME/CFS and compare their microbial content to technical controls as well as three control groups: individuals with alternatively diagnosed chronic Lyme syndrome (N = 13), systemic lupus erythematosus (N = 11), and healthy controls (N = 25). We found that the majority of sequencing reads were removed during host subtraction, thus there was very low microbial RNA content in the plasma. The effects of sample batching and contamination during sample processing proved to outweigh the effects of study group on microbial RNA content, as the few differences in bacterial or viral RNA abundance we did observe between study groups were most likely caused by contamination and batch effects. Our results highlight the importance of including negative controls in all metagenomic analyses, since there was considerable overlap between bacterial content identified in study samples and control samples. For example, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodes were found in both study samples and plasma-free negative controls. Many of the taxonomic groups we saw in our plasma-free negative control samples have previously been associated with diseases, including ME/CFS, demonstrating how incorrect conclusions may arise if controls are not used and batch effects not accounted for.
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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.