ArticleNature genetics2011
A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase.
Article in Nature genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- Detecting fitness epistasis in recently admixed populations with genome-wide data.BMC genomics · 2020Pooled it
- Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.PLoS pathogens · 2015Trial
- Trial
- Design of an immunogen containing multidimensionally conserved and immunogenic parts of the HIV proteome.PLoS computational biology · 2026Article
- On learning functions over biological sequence space: relating Gaussian process priors, regularization, and gauge fixing.Journal of mathematical biology · 2026Article
- Epistatic hotspots organize antibody fitness landscape and boost evolvability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The simplicity of protein sequence-function relationships.Nature communications · 2024Article
- Positive epistasis drives clavulanic acid resistance in double mutant libraries of BlaC β-lactamase.Communications biology · 2024Article
- The simplicity of protein sequence-function relationships.bioRxiv : the preprint server for biology · 2024Article
- Higher-order epistasis and phenotypic prediction.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A Family of Fitness Landscapes Modeled through Gene Regulatory Networks.Entropy (Basel, Switzerland) · 2022Article
- A Two-Level, Intramutant Spectrum Haplotype Profile of Hepatitis C Virus Revealed by Self-Organized Maps.Microbiology spectrum · 2021Article
- Treating symptomatic infections and the co-evolution of virulence and drug resistance.Peer community journal · 2021Article
- Long-term experimental evolution of HIV-1 reveals effects of environment and mutational history.PLoS biology · 2020Article
- Pre-existing resistance in the latent reservoir can compromise VRC01 therapy during chronic HIV-1 infection.PLoS computational biology · 2020Article
- Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease.PLoS genetics · 2020Article
- A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection.PLoS pathogens · 2020Article
- Minimum epistasis interpolation for sequence-function relationships.Nature communications · 2020Article
- Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.Nature communications · 2020Article
- Model genotype-phenotype mappings and the algorithmic structure of evolution.Journal of the Royal Society, Interface · 2019Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of a quantitative understanding of viral evolution and the fitness landscape in HIV-1 drug resistance is a formidable challenge given the large number of available drugs and drug resistance mutations. We analyzed a dataset measuring the in vitro fitness of 70,081 virus samples isolated from HIV-1 subtype B infected individuals undergoing routine drug resistance testing. We assayed virus samples for in vitro replicative capacity in the absence of drugs as well as in the presence of 15 individual drugs. We employed a generalized kernel ridge regression to estimate main fitness effects and epistatic interactions of 1,859 single amino acid variants found within the HIV-1 protease and reverse transcriptase sequences. Models including epistatic interactions predict an average of 54.8% of the variance in replicative capacity across the 16 different environments and substantially outperform models based on main fitness effects only. We find that the fitness landscape of HIV-1 protease and reverse transcriptase is characterized by strong epistasis.
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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.