ArticlePLoS computational biology2012
Highly sensitive and specific detection of rare variants in mixed viral populations from massively parallel sequence data.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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
72 citing papers in PubMed, 139 citations in OpenAlex.
- Trial
- Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.PloS one · 2014Trial
- Epidemiological surveillance and phylogenetic diversity of Orthohantavirus hantanense using high-fidelity nanopore sequencing, Republic of Korea.PLoS neglected tropical diseases · 2025Article
- A Development of Rapid Whole-Genome Sequencing ofViruses · 2023Article
- Taxonomically Restricted Genes in Bacillus may Form Clusters of Homologs and Can be Traced to a Large Reservoir of Noncoding Sequences.Genome biology and evolution · 2023Article
- Covariation of viral recombination with single nucleotide variants during virus evolution revealed by CoVaMa.Nucleic acids research · 2022Article
- High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance.Computational and structural biotechnology journal · 2022Review
- Accurate assembly of minority viral haplotypes from next-generation sequencing through efficient noise reduction.Nucleic acids research · 2021Article
- Detecting and phasing minor single-nucleotide variants from long-read sequencing data.Nature communications · 2021Article
- Article
- Epidemiological data analysis of viral quasispecies in the next-generation sequencing era.Briefings in bioinformatics · 2021Review
- Strategy and Performance Evaluation of Low-Frequency Variant Calling for SARS-CoV-2 Using Targeted Deep Illumina Sequencing.Frontiers in microbiology · 2021Article
- Evaluation of haplotype callers for next-generation sequencing of viruses.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Next-Generation Sequencing for HIV Drug Resistance Testing: Laboratory, Clinical, and Implementation Considerations.Viruses · 2020Review
- Analysis of unusual and signature APOBEC-mutations in HIV-1 pol next-generation sequences.PloS one · 2020Article
- DISSEQT-DIStribution-based modeling of SEQuence space Time dynamics.Virus evolution · 2019Article
- Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors.Hepatology (Baltimore, Md.) · 2019Article
- Interpreting Viral Deep Sequencing Data with GLUE.Viruses · 2019Article
- High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses.Journal of virology · 2018Article
- Evaluating the performance of tools used to call minority variants from whole genome short-read data.Wellcome open research · 2018Article
12 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
16 authors at 3 institutions in 1 country.
Funding
Abstract
Viruses diversify over time within hosts, often undercutting the effectiveness of host defenses and therapeutic interventions. To design successful vaccines and therapeutics, it is critical to better understand viral diversification, including comprehensively characterizing the genetic variants in viral intra-host populations and modeling changes from transmission through the course of infection. Massively parallel sequencing technologies can overcome the cost constraints of older sequencing methods and obtain the high sequence coverage needed to detect rare genetic variants (< 1%) within an infected host, and to assay variants without prior knowledge. Critical to interpreting deep sequence data sets is the ability to distinguish biological variants from process errors with high sensitivity and specificity. To address this challenge, we describe V-Phaser, an algorithm able to recognize rare biological variants in mixed populations. V-Phaser uses covariation (i.e. phasing) between observed variants to increase sensitivity and an expectation maximization algorithm that iteratively recalibrates base quality scores to increase specificity. Overall, V-Phaser achieved > 97% sensitivity and > 97% specificity on control read sets. On data derived from a patient after four years of HIV-1 infection, V-Phaser detected 2,015 variants across the -10 kb genome, including 603 rare variants (< 1% frequency) detected only using phase information. V-Phaser identified variants at frequencies down to 0.2%, comparable to the detection threshold of allele-specific PCR, a method that requires prior knowledge of the variants. The high sensitivity and specificity of V-Phaser enables identifying and tracking changes in low frequency variants in mixed populations such as RNA viruses.
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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.