Evidence map›Paper›PMID 32669542›Full record

ArticleNature communications2020

Large-scale DNA-based phenotypic recording and deep learning enable highly accurate sequence-function mapping.

Simon Höllerer, Laetitia Papaxanthos, Anja Cathrin Gumpinger, Katrin Fischer, Christian Beisel, Karsten Borgwardt, Yaakov Benenson, Markus Jeschek

Open access · goldAbstract read
In one paragraph

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 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
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

35 citing papers in PubMed, 67 citations in OpenAlex.

  1. Deep learning-drivenSynthetic and systems biotechnology · 2027
    Article
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  5. Probiotic-Based Materials as Living Therapeutics.Advanced materials (Deerfield Beach, Fla.) · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Overview and Prospects of DNA Sequence Visualization.International journal of molecular sciences · 2025
    Review
  12. Optimization of regulatory DNA with active learning.Computational and structural biotechnology journal · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  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

8 authors at 2 institutions in 1 country.

Simon Höllerer *Department of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1328-9427
Laetitia Papaxanthos *Department of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.ORCID http://orcid.org/0000-0002-0521-621X
Anja Cathrin GumpingerDepartment of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.ORCID http://orcid.org/0000-0003-0194-1809
Katrin FischerDepartment of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.ORCID http://orcid.org/0000-0002-6566-3038
Christian BeiselDepartment of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.
Karsten BorgwardtDepartment of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland. karsten.borgwardt@bsse.ethz.ch.ORCID http://orcid.org/0000-0001-7221-2393
Yaakov BenensonDepartment of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland. kobi.benenson@bsse.ethz.ch.ORCID http://orcid.org/0000-0003-1880-6507
Markus JeschekDepartment of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland. markus.jeschek@bsse.ethz.ch.ORCID http://orcid.org/0000-0003-1317-2461
ETH Zurich · CHSIB Swiss Institute of Bioinformatics · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Predicting effects of gene regulatory elements (GREs) is a longstanding challenge in biology. Machine learning may address this, but requires large datasets linking GREs to their quantitative function. However, experimental methods to generate such datasets are either application-specific or technically complex and error-prone. Here, we introduce DNA-based phenotypic recording as a widely applicable, practicable approach to generate large-scale sequence-function datasets. We use a site-specific recombinase to directly record a GRE's effect in DNA, enabling readout of both sequence and quantitative function for extremely large GRE-sets via next-generation sequencing. We record translation kinetics of over 300,000 bacterial ribosome binding sites (RBSs) in >2.7 million sequence-function pairs in a single experiment. Further, we introduce a deep learning approach employing ensembling and uncertainty modelling that predicts RBS function with high accuracy, outperforming state-of-the-art methods. DNA-based phenotypic recording combined with deep learning represents a major advance in our ability to predict function from genetic sequence.

Indexed as

Deep LearningPhenotypeBinding SitesComputational BiologyDatasets as TopicEscherichia coliGene Knockout TechniquesGenome, BacterialHigh-Throughput Nucleotide SequencingMolecular Sequence AnnotationRegulatory Sequences, Nucleic AcidRibosomesSequence Analysis, DNA

Identifiers

PMID32669542
PMCPMC7363850
OpenAlexW3043211404

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.