IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-42405-0.html
   My bibliography  Save this article

Transposable elements mediate genetic effects altering the expression of nearby genes in colorectal cancer

Author

Listed:
  • Nikolaos M. R. Lykoskoufis

    (University of Geneva Medical School
    University of Geneva
    Swiss Institute of Bioinformatics
    NGS-AI JSR Life Sciences, Route de la Corniche 3)

  • Evarist Planet

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Halit Ongen

    (University of Geneva Medical School
    University of Geneva
    Swiss Institute of Bioinformatics)

  • Didier Trono

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Emmanouil T. Dermitzakis

    (University of Geneva Medical School
    University of Geneva
    Swiss Institute of Bioinformatics)

Abstract

Transposable elements (TEs) are prevalent repeats in the human genome, play a significant role in the regulome, and their disruption can contribute to tumorigenesis. However, TE influence on gene expression in cancer remains unclear. Here, we analyze 275 normal colon and 276 colorectal cancer samples from the SYSCOL cohort, discovering 10,231 and 5,199 TE-expression quantitative trait loci (eQTLs) in normal and tumor tissues, respectively, of which 376 are colorectal cancer specific eQTLs, likely due to methylation changes. Tumor-specific TE-eQTLs show greater enrichment of transcription factors, compared to shared TE-eQTLs suggesting specific regulation of their expression in tumor. Bayesian networks reveal 1,766 TEs as mediators of genetic effects, altering the expression of 1,558 genes, including 55 known cancer driver genes and show that tumor-specific TE-eQTLs trigger the driver capability of TEs. These insights expand our knowledge of cancer drivers, deepening our understanding of tumorigenesis and presenting potential avenues for therapeutic interventions.

Suggested Citation

  • Nikolaos M. R. Lykoskoufis & Evarist Planet & Halit Ongen & Didier Trono & Emmanouil T. Dermitzakis, 2024. "Transposable elements mediate genetic effects altering the expression of nearby genes in colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-42405-0
    DOI: 10.1038/s41467-023-42405-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42405-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42405-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Olivier Delaneau & Halit Ongen & Andrew A. Brown & Alexandre Fort & Nikolaos I. Panousis & Emmanouil T. Dermitzakis, 2017. "A complete tool set for molecular QTL discovery and analysis," Nature Communications, Nature, vol. 8(1), pages 1-7, August.
    2. Halit Ongen & Claus L. Andersen & Jesper B. Bramsen & Bodil Oster & Mads H. Rasmussen & Pedro G. Ferreira & Juan Sandoval & Enrique Vidal & Nicola Whiffin & Alexandra Planchon & Ismael Padioleau & Deb, 2014. "Putative cis-regulatory drivers in colorectal cancer," Nature, Nature, vol. 512(7512), pages 87-90, August.
    3. Michaël Imbeault & Pierre-Yves Helleboid & Didier Trono, 2017. "KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks," Nature, Nature, vol. 543(7646), pages 550-554, March.
    4. Scutari, Marco, 2010. "Learning Bayesian Networks with the bnlearn R Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 35(i03).
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Andrew A. Brown & Juan J. Fernandez-Tajes & Mun-gwan Hong & Caroline A. Brorsson & Robert W. Koivula & David Davtian & Théo Dupuis & Ambra Sartori & Theodora-Dafni Michalettou & Ian M. Forgie & Jonath, 2023. "Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Prabal Das & D. A. Sachindra & Kironmala Chanda, 2022. "Machine Learning-Based Rainfall Forecasting with Multiple Non-Linear Feature Selection Algorithms," Water Resources Management: An International Journal, Published for the European Water Resources Association (EWRA), Springer;European Water Resources Association (EWRA), vol. 36(15), pages 6043-6071, December.
    3. Vuong, Quan-Hoang & La, Viet-Phuong, 2019. "The bayesvl R package. User guide v0.8.1," OSF Preprints w5dx6, Center for Open Science.
    4. F. Cugnata & G. Perucca & S. Salini, 2017. "Bayesian networks and the assessment of universities' value added," Journal of Applied Statistics, Taylor & Francis Journals, vol. 44(10), pages 1785-1806, July.
    5. Roland R. Ramsahai, 2020. "Connecting actuarial judgment to probabilistic learning techniques with graph theory," Papers 2007.15475, arXiv.org.
    6. Tang, Kayu & Parsons, David J. & Jude, Simon, 2019. "Comparison of automatic and guided learning for Bayesian networks to analyse pipe failures in the water distribution system," Reliability Engineering and System Safety, Elsevier, vol. 186(C), pages 24-36.
    7. Myriam Patricia Cifuentes & Clara Mercedes Suarez & Ricardo Cifuentes & Noel Malod-Dognin & Sam Windels & Jose Fernando Valderrama & Paul D. Juarez & R. Burciaga Valdez & Cynthia Colen & Charles Phill, 2022. "Big Data to Knowledge Analytics Reveals the Zika Virus Epidemic as Only One of Multiple Factors Contributing to a Year-Over-Year 28-Fold Increase in Microcephaly Incidence," IJERPH, MDPI, vol. 19(15), pages 1-21, July.
    8. Silvia de Juan & Maria Dulce Subida & Andres Ospina-Alvarez & Ainara Aguilar & Miriam Fernandez, 2020. "Disentangling the socio-ecological drivers behind illegal fishing in a small-scale fishery managed by a TURF system," Papers 2012.08970, arXiv.org.
    9. Meineri, Eric & Dahlberg, C. Johan & Hylander, Kristoffer, 2015. "Using Gaussian Bayesian Networks to disentangle direct and indirect associations between landscape physiography, environmental variables and species distribution," Ecological Modelling, Elsevier, vol. 313(C), pages 127-136.
    10. Michail Tsagris, 2021. "A New Scalable Bayesian Network Learning Algorithm with Applications to Economics," Computational Economics, Springer;Society for Computational Economics, vol. 57(1), pages 341-367, January.
    11. Michael J. Brusco & Douglas Steinley & Ashley L. Watts, 2022. "Disentangling relationships in symptom networks using matrix permutation methods," Psychometrika, Springer;The Psychometric Society, vol. 87(1), pages 133-155, March.
    12. Sangsung Park & Sunghae Jun, 2020. "Patent Keyword Analysis of Disaster Artificial Intelligence Using Bayesian Network Modeling and Factor Analysis," Sustainability, MDPI, vol. 12(2), pages 1-11, January.
    13. Fasil Tekola-Ayele & Xuehuo Zeng & Suvo Chatterjee & Marion Ouidir & Corina Lesseur & Ke Hao & Jia Chen & Markos Tesfaye & Carmen J. Marsit & Tsegaselassie Workalemahu & Ronald Wapner, 2022. "Placental multi-omics integration identifies candidate functional genes for birthweight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. Federica Cugnata & Silvia Salini & Elena Siletti, 2021. "Deepening Well-Being Evaluation with Different Data Sources: A Bayesian Networks Approach," IJERPH, MDPI, vol. 18(15), pages 1-10, July.
    15. Bibartiu, Otto & Dürr, Frank & Rothermel, Kurt & Ottenwälder, Beate & Grau, Andreas, 2021. "Scalable k-out-of-n models for dependability analysis with Bayesian networks," Reliability Engineering and System Safety, Elsevier, vol. 210(C).
    16. Lingfei Wang, 2021. "Single-cell normalization and association testing unifying CRISPR screen and gene co-expression analyses with Normalisr," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    17. Bruce G. Marcot & Anca M. Hanea, 2021. "What is an optimal value of k in k-fold cross-validation in discrete Bayesian network analysis?," Computational Statistics, Springer, vol. 36(3), pages 2009-2031, September.
    18. Ryan G. Lim & Osama Al-Dalahmah & Jie Wu & Maxwell P. Gold & Jack C. Reidling & Guomei Tang & Miriam Adam & David K. Dansu & Hye-Jin Park & Patrizia Casaccia & Ricardo Miramontes & Andrea M. Reyes-Ort, 2022. "Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    19. Robert Stojnic & Audrey Qiuyan Fu & Boris Adryan, 2012. "A Graphical Modelling Approach to the Dissection of Highly Correlated Transcription Factor Binding Site Profiles," PLOS Computational Biology, Public Library of Science, vol. 8(11), pages 1-13, November.
    20. Yi Tan & Prakash P. Shenoy & Ben Sherwood & Catherine Shenoy & Melinda Gaddy & Mary E. Oehlert, 2024. "Bayesian Network Models for PTSD Screening in Veterans," INFORMS Journal on Computing, INFORMS, vol. 36(2), pages 495-509, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-42405-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.