Cited by 177Genomics and Chromatin DynamicsGene Regulatory Network AnalysisRNA and protein synthesis mechanisms

Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure

Open access
Zrimec, Jan, Börlin, Christoph S., Buric, Filip, Muhammad, Azam Sheikh, Chen, Rhongzen, Siewers, Verena, Verendel, Vilhelm, Nielsen, Jens +2 more·2020·Nature Communications

Published version of a preprint

Abstract

Abstract Understanding the genetic regulatory code governing gene expression is an important challenge in molecular biology. However, how individual coding and non-coding regions of the gene regulatory structure interact and contribute to mRNA expression levels remains unclear. Here we apply deep learning on over 20,000 mRNA datasets to examine the genetic regulatory code controlling mRNA abundance in 7 model organisms ranging from bacteria to Human. In all organisms, we can predict mRNA abundance directly from DNA sequence, with up to 82% of the variation of transcript levels encoded in the gene regulatory structure. By searching for DNA regulatory motifs across the gene regulatory structure, we discover that motif interactions could explain the whole dynamic range of mRNA levels. Co-evolution across coding and non-coding regions suggests that it is not single motifs or regions, but the entire gene regulatory structure and specific combination of regulatory elements that define gene expression levels.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-020-19921-4

Cites

158 of 158 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Deep learning has been applied and shown great performance in modelling chemical spaces, gene expression, enzyme-related parameters such as enzyme affinity and EC numbers.

    “Deep learning has been applied and shown great performance in modelling chemical spaces 18 , gene expression 19 , enzyme-related parameters such as enzyme affinity 20 and EC numbers 21 .”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. [82]Kuhn, M. & Johnson, K. Applied predictive modelling. (Springer, New York, Heidelberg, Dordrecht, London, 2013).
  2. [85]Shalizi, C. Advanced data analysis from an elementary point of view. (Cambridge University Press, 2013).

Cited by

Sorted by citations

Authors
Zrimec, J., Börlin, C. S., Buric, F., Muhammad, A. S., Chen, R., Siewers, V., Verendel, V., Nielsen, J., Töpel, M., & Zelezniak, A.
Affiliations
  • Chalmers University of Technology (SE)
  • University of Gothenburg (SE)
  • Science for Life Laboratory (SE)
Corresponding author
Zelezniak, Aleksej
Venue
Nature Communications
Published
2020-12-01
Volume
11
Issue
1
Pages
6141-6141
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3108101741
Cited by
174
References
154
Citations by year
2026: 19 · 2025: 35 · 2024: 42 · 2023: 28 · 2022: 27 · 2021: 21 · 2020: 2
FWCI
6.32
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Chalmers Research (Chalmers University of Technology) (submittedVersion)
Funders
  • Nvidia
  • European Commission (722287)
  • Chalmers Tekniska Högskola
  • Science for Life Laboratory
  • Novo Nordisk Fonden (NNF10CC1016517)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
gene expression regulation, mRNA levels, DNA sequences, regulatory motifs, coevolution, non-coding regions, coding sequences, deep learning, transcriptome, model organisms
MeSH terms
Deep Learning, Animals, Bacteria, Base Sequence, Drosophila melanogaster, Gene Expression Regulation, Humans, Regulatory Sequences, Nucleic Acid, RNA, Messenger, Saccharomyces cerevisiae, Evolution, Molecular, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review