ArticleNature communications2020
Biophysical ambiguities prevent accurate genetic prediction.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 49 citations in OpenAlex.
- Seven complete comparative maps of allosteric mutations in a protein family.Nature communications · 2026Article
- Deconvolving mutation effects on protein stability and function with disentangled protein language models.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary pathways in epistatic mechanical networks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Generalizable and scalable protein stability prediction with rewired protein generative models.Nature communications · 2025Article
- A method for predicting enzyme substrate specificity residues using homologous sequence information.Protein science : a publication of the Protein Society · 2025Article
- MoCHI: neural networks to fit interpretable models and quantify energies, energetic couplings, epistasis, and allostery from deep mutational scanning data.Genome biology · 2024Article
- Multiplexed profiling of intracellular protein abundance, activity, interactions and druggability with LABEL-seq.Nature methods · 2024Article
- MuToN Quantifies Binding Affinity Changes upon Protein Mutations by Geometric Deep Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A parameterized two-domain thermodynamic model explains diverse mutational effects on protein allostery.eLife · 2024Article
- Multiplexed, multimodal profiling of the intracellular activity, interactions, and druggability of protein variants using LABEL-seq.bioRxiv : the preprint server for biology · 2024Article
- Characterizing glucokinase variant mechanisms using a multiplexed abundance assay.Genome biology · 2024Article
- A parametrized two-domain thermodynamic model explains diverse mutational effects on protein allostery.bioRxiv : the preprint server for biology · 2024Article
- Article
- Mechanistic causes of sign epistasis and its applications.Frontiers in genetics · 2024Review
- Dominance vs epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles.Nature communications · 2023Article
- Discovering functionally important sites in proteins.Nature communications · 2023Article
- Deep mutational scanning: A versatile tool in systematically mapping genotypes to phenotypes.Frontiers in genetics · 2023Review
- Precision engineering of biological function with large-scale measurements and machine learning.PloS one · 2023Article
- Revealing modifier variations characterizations for elucidating the genetic basis of human phenotypic variations.Human genetics · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A goal of biology is to predict how mutations combine to alter phenotypes, fitness and disease. It is often assumed that mutations combine additively or with interactions that can be predicted. Here, we show using simulations that, even for the simple example of the lambda phage transcription factor CI repressing a gene, this assumption is incorrect and that perfect measurements of the effects of mutations on a trait and mechanistic understanding can be insufficient to predict what happens when two mutations are combined. This apparent paradox arises because mutations can have different biophysical effects to cause the same change in a phenotype and the outcome in a double mutant depends upon what these hidden biophysical changes actually are. Pleiotropy and non-monotonic functions further confound prediction of how mutations interact. Accurate prediction of phenotypes and disease will sometimes not be possible unless these biophysical ambiguities can be resolved using additional measurements.
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What OpenQuestion holds
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.