Base-resolution models of transcription factor binding reveal soft motif syntax Article Swipe
Žiga Avsec
,
Melanie Weilert
,
Avanti Shrikumar
,
Sabrina Krueger
,
Amr M. Alexandari
,
Khyati Dalal
,
Robin Fropf
,
Charles E. McAnany
,
Julien Gagneur
,
Anshul Kundaje
,
Julia Zeitlinger
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1101/737981
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1101/737981
Summary The arrangement of transcription factor (TF) binding motifs (syntax) is an important part of the cis-regulatory code, yet remains elusive. We introduce a deep learning model, BPNet, that uses DNA sequence to predict base-resolution ChIP-nexus binding profiles of pluripotency TFs. We develop interpretation tools to learn predictive motif representations and identify soft syntax rules for cooperative TF binding interactions. Strikingly, Nanog preferentially binds with helical periodicity, and TFs often cooperate in a directional manner, which we validate using CRISPR-induced point mutations. Our model represents a powerful general approach to uncover the motifs and syntax of cis-regulatory sequences in genomics data. Highlights The neural network BPNet accurately predicts TF binding data at base-resolution. Model interpretation discovers TF motifs and TF interactions dependent on soft syntax. Motifs for Nanog and partners are preferentially spaced at ∼10.5 bp periodicity. Directional cooperativity is validated: Sox2 enhances Nanog binding, but not vice versa.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/737981
- OA Status
- green
- Cited By
- 39
- References
- 159
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3043517361
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3043517361Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/737981Digital Object Identifier
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Base-resolution models of transcription factor binding reveal soft motif syntaxWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2019Year of publication
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2019-08-21Full publication date if available
- Authors
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Žiga Avsec, Melanie Weilert, Avanti Shrikumar, Sabrina Krueger, Amr M. Alexandari, Khyati Dalal, Robin Fropf, Charles E. McAnany, Julien Gagneur, Anshul Kundaje, Julia ZeitlingerList of authors in order
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1101/737981Direct OA link when available
- Concepts
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Computational biology, Transcription factor, Enhancer, Binding site, Cooperativity, Syntax, PAX6, Biology, Genetics, Computer science, Artificial intelligence, GeneTop concepts (fields/topics) attached by OpenAlex
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39Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 2, 2023: 3, 2022: 7, 2021: 10Per-year citation counts (last 5 years)
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159Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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