Evidence map›Paper›PMID 31636460›Full record

ArticleNature methods2019

Unified rational protein engineering with sequence-based deep representation learning.

Ethan C Alley, Grigory Khimulya, Surojit Biswas, Mohammed AlQuraishi, George M Church

Abstract read
In one paragraph

Article in Nature methods, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 503 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
503citing papers in PubMed, 1 pooled it
–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

503 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  9. Leveraging latent space models for enzyme discovery and sampling.Proceedings of the National Academy of Sciences of the United States of America · 2026
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443 more citing papers are in PubMed but not listed here.

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

5 authors.

Ethan C Alley *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Grigory Khimulya *
Surojit Biswas *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Mohammed AlQuraishiDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6817-1322
George M ChurchWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. gchurch@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0003-3535-2076

Funding

Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
TRANSLATIONAL PHARMACOLOGY COREP50GM107618 · NIGMS · HARVARD MEDICAL SCHOOL · PI GOLAN, DAVID E. · 2014 to 2018
$10.8M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA · 2018 to 2022
$10.8M
NCI NIH HHS U54 CA225088NHGRI NIH HHS T32 HG002295NIGMS NIH HHS P50 GM107618
6 · The paper itself

Abstract

Rational protein engineering requires a holistic understanding of protein function. Here, we apply deep learning to unlabeled amino-acid sequences to distill the fundamental features of a protein into a statistical representation that is semantically rich and structurally, evolutionarily and biophysically grounded. We show that the simplest models built on top of this unified representation (UniRep) are broadly applicable and generalize to unseen regions of sequence space. Our data-driven approach predicts the stability of natural and de novo designed proteins, and the quantitative function of molecularly diverse mutants, competitively with the state-of-the-art methods. UniRep further enables two orders of magnitude efficiency improvement in a protein engineering task. UniRep is a versatile summary of fundamental protein features that can be applied across protein engineering informatics.

Indexed as

Deep LearningAmino Acid SequenceMutationProtein EngineeringProtein Stability

Identifiers

PMID31636460
PMCPMC7067682

What OpenQuestion holds

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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.