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  • Grapotte, Mathys (author)

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-06-02
  • Springer Science and Business Media LLC,2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-309717
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-309717URI
  • https://doi.org/10.1038/s41467-021-23143-7DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-211977URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20220309Correction in: Nature Communications, Volume 13, Issue 1, Article Number 1200, DOI 10.1038/s41467-022-28758-y, WOS:000771136200018
  • For correction, see: Grapotte, M., Saraswat, M., Bessière, C. et al. Author Correction: Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network. Nat Commun 13, 1200 (2022). DOI: 10.1038/s41467-022-28758-y
  • Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Forsberg, MattiasKTH,Systembiologi(Swepub:kth)u1l9h7ku (author)
  • Oksvold, PerKTH,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1qey3lv (author)
  • Sivertsson, ÅsaKTH,Science for Life Laboratory, SciLifeLab,Systembiologi(Swepub:kth)u195d5b0 (author)
  • Sjöstedt, EvelinaKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u12iezpl (author)
  • Uhlén, MathiasKTH,Science for Life Laboratory, SciLifeLab,Albanova VinnExcellence Center for Protein Technology, ProNova,Systembiologi(Swepub:kth)u1dulvmw (author)
  • von Feilitzen, KalleKTH,Systembiologi,Proteinteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1dbmi38 (author)
  • Zwahlen, MartinKTH,Science for Life Laboratory, SciLifeLab,Systembiologi(Swepub:kth)u1fcjpxe (author)
  • Elofsson, Arne,1966-Stockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)aelof (author)
  • Sachenkova, OxanaStockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)osach (author)
  • Bréhélin, Laurent (author)
  • Lecellier, Charles-Henri (author)
  • KTHSystembiologi (creator_code:org_t)

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  • In:Nature Communications: Springer Science and Business Media LLC2041-1723

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