Evidence map›Paper›PMID 37308471›Full record

ArticleNature communications2023

Machine learning optimization of candidate antibody yields highly diverse sub-nanomolar affinity antibody libraries.

Lin Li, Esther Gupta, John Spaeth, Leslie Shing, Rafael Jaimes, Emily Engelhart, Randolph Lopez, Rajmonda S Caceres, Tristan Bepler, Matthew E Walsh

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing 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

56 citing papers in PubMed.

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  5. Multiobjective VScience advances · 2026
    Article
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  9. Review
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  15. AI-Driven De Novo Binder Design: From Structure Prediction to Closed-Loop Optimization.Computational and structural biotechnology journal · 2026
    Review
  16. Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025
    Article
  17. Article
  18. Article
  19. Review
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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

10 authors.

Lin LiMassachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA. Lin.Li@LL.MIT.EDU.ORCID 0000-0003-4087-6149
Esther GuptaMassachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA.
John SpaethMassachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA.
Leslie ShingMassachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA.ORCID 0000-0003-3677-6698
Rafael JaimesMassachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA.ORCID 0000-0002-5493-0399
Emily EngelhartA-Alpha Bio, Inc., Seattle, WA, USA.
Randolph LopezA-Alpha Bio, Inc., Seattle, WA, USA.
Rajmonda S Caceres *Massachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA.
Tristan Bepler *Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0001-5595-9954
Matthew E Walsh *Massachusetts Institute of Technology Lincoln Laboratory, Lexington, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic antibodies are an important and rapidly growing drug modality. However, the design and discovery of early-stage antibody therapeutics remain a time and cost-intensive endeavor. Here we present an end-to-end Bayesian, language model-based method for designing large and diverse libraries of high-affinity single-chain variable fragments (scFvs) that are then empirically measured. In a head-to-head comparison with a directed evolution approach, we show that the best scFv generated from our method represents a 28.7-fold improvement in binding over the best scFv from the directed evolution. Additionally, 99% of designed scFvs in our most successful library are improvements over the initial candidate scFv. By comparing a library's predicted success to actual measurements, we demonstrate our method's ability to explore tradeoffs between library success and diversity. Results of our work highlight the significant impact machine learning models can have on scFv development. We expect our method to be broadly applicable and provide value to other protein engineering tasks.

Indexed as

LanguageSingle-Chain AntibodiesBayes TheoremGene LibraryMachine LearningSingle-Chain Antibodies

Identifiers

PMID37308471
PMCPMC10258481

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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.