Evidence map›Paper›PMID 34292650›Full record

ArticleMolecular systems biology2021

Exploring amino acid functions in a deep mutational landscape.

Alistair S Dunham, Pedro Beltrao

Abstract read
In one paragraph

Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed.

  1. Toward Advanced Quantitative Prediction of Missense Variant Effects.International journal of molecular sciences · 2026
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  2. Article
  3. Article
  4. Review
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  7. Supervised learning of protein variant effects across large-scale mutagenesis datasets.Protein science : a publication of the Protein Society · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Evolutionary analysis ofFrontiers in plant science · 2026
    Article
  12. Article
  13. Systematic and proactive evaluation of AIRE missense variant effects.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Alistair S DunhamEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.ORCID 0000-0001-9076-3025
Pedro BeltraoEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.ORCID 0000-0002-2724-7703

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amino acids fulfil a diverse range of roles in proteins, each utilising its chemical properties in different ways in different contexts to create required functions. For example, cysteines form disulphide or hydrogen bonds in different circumstances and charged amino acids do not always make use of their charge. The repertoire of amino acid functions and the frequency at which they occur in proteins remains understudied. Measuring large numbers of mutational consequences, which can elucidate the role an amino acid plays, was prohibitively time-consuming until recent developments in deep mutational scanning. In this study, we gathered data from 28 deep mutational scanning studies, covering 6,291 positions in 30 proteins, and used the consequences of mutation at each position to define a mutational landscape. We demonstrated rich relationships between this landscape and biophysical or evolutionary properties. Finally, we identified 100 functional amino acid subtypes with a data-driven clustering analysis and studied their features, including their frequencies and chemical properties such as tolerating polarity, hydrophobicity or being intolerant of charge or specific amino acids. The mutational landscape and amino acid subtypes provide a foundational catalogue of amino acid functional diversity, which will be refined as the number of studied protein positions increases.

Indexed as

Amino AcidsProteinsBiological EvolutionMutationAmino AcidsProteinsamino acid functiondeep mutational scanningmutational consequencesprotein structureunsupervised learning

Identifiers

PMID34292650
PMCPMC8297461

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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.