دورية أكاديمية
Dissecting the cis -regulatory syntax of transcription initiation with deep learning.
| العنوان: | Dissecting the cis -regulatory syntax of transcription initiation with deep learning. |
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| المؤلفون: | Cochran K; Department of Computer Science, Stanford University, Stanford, CA, USA., Yin M; The Harker School, San Jose, CA, USA., Mantripragada A; The Harker School, San Jose, CA, USA., Schreiber J; Department of Genetics, Stanford University, Stanford, CA, USA., Marinov GK; Department of Genetics, Stanford University, Stanford, CA, USA., Kundaje A; Department of Computer Science, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University, Stanford, CA, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 May 31. Date of Electronic Publication: 2024 May 31. |
| نوع المنشور: | Journal Article; Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Despite extensive characterization of mammalian Pol II transcription, the DNA sequence determinants of transcription initiation at a third of human promoters and most enhancers remain poorly understood. Hence, we trained and interpreted a neural network called ProCapNet that accurately models base-resolution initiation profiles from PRO-cap experiments using local DNA sequence. ProCapNet learns sequence motifs with distinct effects on initiation rates and TSS positioning and uncovers context-specific cryptic initiator elements intertwined within other TF motifs. ProCapNet annotates predictive motifs in nearly all actively transcribed regulatory elements across multiple cell-lines, revealing a shared cis -regulatory logic across promoters and enhancers mediated by a highly epistatic sequence syntax of cooperative and competitive motif interactions. ProCapNet models of RAMPAGE profiles measuring steady-state RNA abundance at TSSs distill initiation signals on par with models trained directly on PRO-cap profiles. ProCapNet learns a largely cell-type-agnostic cis -regulatory code of initiation complementing sequence drivers of cell-type-specific chromatin state critical for accurate prediction of cell-type-specific transcription initiation. Competing Interests: Competing Interests A.K. is on the scientific advisory board of SerImmune, AIN-ovo, TensorBio and OpenTargets. A.K was a scientific co-founder of RavelBio, a paid consultant with Illumina, was on the SAB of PatchBio and owns shares in DeepGenomics, Immunai, Freenome and Illumina. K.C. is a paid consultant with ImmunoVec and owns shares in Inceptive Nucleics. J.S. is a paid consultant for Talus Bioscience and ImmunoVec. All other authors have no competing interests to declare. |
| معلومات مُعتمدة: | U01 HG009431 United States HG NHGRI NIH HHS; U01 HG012069 United States HG NHGRI NIH HHS; U24 HG007234 United States HG NHGRI NIH HHS |
| تواريخ الأحداث: | Date Created: 20240610 Latest Revision: 20240617 |
| رمز التحديث: | 20240617 |
| مُعرف محوري في PubMed: | PMC11160661 |
| DOI: | 10.1101/2024.05.28.596138 |
| PMID: | 38853896 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.05.28.596138 |
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