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Discovery of physiological and cancer-related regulators of 3’ UTR processing with KAPAC

View ORCID ProfileAndreas J. Gruber, Ralf Schmidt, Souvik Ghosh, Georges Martin, Andreas R. Gruber, Erik van Nimwegen, View ORCID ProfileMihaela Zavolan
doi: https://doi.org/10.1101/195958
Andreas J. Gruber
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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  • ORCID record for Andreas J. Gruber
Ralf Schmidt
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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Souvik Ghosh
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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Georges Martin
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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Andreas R. Gruber
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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Erik van Nimwegen
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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Mihaela Zavolan
1Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland
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  • ORCID record for Mihaela Zavolan
  • For correspondence: mihaela.zavolan@unibas.ch
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Abstract

3’ UTR length is regulated in relation to cellular state. To uncover key regulators of poly(A) site (PAS) use in specific conditions, we have developed PAQR, a method for quantifying PAS use from RNA sequencing data and KAPAC, an approach that infers activities of oligomeric sequence motifs on PAS choice. Application of PAQR and KAPAC to RNA sequencing data from normal and tumor tissue samples uncovered sequence motifs that can explain changes in cleavage and polyadenylation in specific cancers. In particular, our analysis points to Polypyrimidine tract binding protein 1 as a regulator of PAS choice in glioblastoma.

  • List of abbreviations

    BCLA
    Bladder Urothelial Carcinoma
    BRCA
    Breast Invasive Carcinoma
    COAD
    Colon Adenocarcinoma
    ESCA
    Esophageal Carcinoma
    GBM
    Glioblastoma Multiforme
    HNSC
    Head and Neck Squamous Cell Carcinoma
    KICH
    Kidney Chromophobe
    KIRC
    Kidney Renal Clear Cell Carcinoma
    KIRP
    Kidney Renal Papillary Cell Carcinoma
    LIHC
    Liver Hepatocellular Carcinoma
    LUAD
    Lung Adenocarcinoma
    LUSC
    Lung Squamous Cell Carcinoma
    PRAD
    Prostate Adenocarcinoma
    READ
    Rectum Adenocarcinoma
    STAD
    Stomach Adenocarcinoma
    THCA
    Thyroid Carcinoma
    UCEC
    Uterine Corpus Endometrial Carcinoma
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    Posted December 01, 2017.
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    Discovery of physiological and cancer-related regulators of 3’ UTR processing with KAPAC
    Andreas J. Gruber, Ralf Schmidt, Souvik Ghosh, Georges Martin, Andreas R. Gruber, Erik van Nimwegen, Mihaela Zavolan
    bioRxiv 195958; doi: https://doi.org/10.1101/195958
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    Discovery of physiological and cancer-related regulators of 3’ UTR processing with KAPAC
    Andreas J. Gruber, Ralf Schmidt, Souvik Ghosh, Georges Martin, Andreas R. Gruber, Erik van Nimwegen, Mihaela Zavolan
    bioRxiv 195958; doi: https://doi.org/10.1101/195958

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