IDEAS home Printed from https://ideas.repec.org/a/bpj/sagmbi/v10y2011i1n3.html
   My bibliography  Save this article

Learning Monotonic Genotype-Phenotype Maps

Author

Listed:
  • Beerenwinkel Niko
  • Knupfer Patrick
  • Tresch Achim

Abstract

Evolutionary escape of pathogens from the selective pressure of immune responses and from medical interventions is driven by the accumulation of mutations. We introduce a statistical model for jointly estimating the dynamics and dependencies among genetic alterations and the associated phenotypic changes. The model integrates conjunctive Bayesian networks, which define a partial order on the occurrences of genetic events, with isotonic regression. The resulting genotype-phenotype map is non-decreasing in the lattice of genotypes. It describes evolutionary escape as a directed process following a phenotypic gradient, such as a monotonic fitness landscape. We present efficient algorithms for parameter estimation and model selection. The model is validated using simulated data and applied to HIV drug resistance data. We find that the effect of many resistance mutations is non-linear and depends on the genetic background in which they occur.

Suggested Citation

  • Beerenwinkel Niko & Knupfer Patrick & Tresch Achim, 2011. "Learning Monotonic Genotype-Phenotype Maps," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 10(1), pages 1-27, January.
    • Handle: RePEc:bpj:sagmbi:v:10:y:2011:i:1:n:3
    DOI: 10.2202/1544-6115.1603
    as

    Download full text from publisher

    File URL: https://doi.org/10.2202/1544-6115.1603
    Download Restriction: For access to full text, subscription to the journal or payment for the individual article is required.
    File URL: https://libkey.io/10.2202/1544-6115.1603?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    References listed on IDEAS

    as
    1. N. Beerenwinkel & S. Sullivant, 2009. "Markov models for accumulating mutations," Biometrika, Biometrika Trust, vol. 96(3), pages 645-661.
    2. Segal Mark R & Barbour Jason D & Grant Robert M, 2004. "Relating HIV-1 Sequence Variation to Replication Capacity via Trees and Forests," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-20, February.
    3. Frank J. Poelwijk & Daniel J. Kiviet & Daniel M. Weinreich & Sander J. Tans, 2007. "Empirical fitness landscapes reveal accessible evolutionary paths," Nature, Nature, vol. 445(7126), pages 383-386, January.
    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. Manhart, Michael & Haldane, Allan & Morozov, Alexandre V., 2012. "A universal scaling law determines time reversibility and steady state of substitutions under selection," Theoretical Population Biology, Elsevier, vol. 82(1), pages 66-76.
    2. Xiang Ge Luo & Jack Kuipers & Niko Beerenwinkel, 2023. "Joint inference of exclusivity patterns and recurrent trajectories from tumor mutation trees," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Hendrik Weisser & André Altmann & Saleta Sierra & Francesca Incardona & Daniel Struck & Anders Sönnerborg & Rolf Kaiser & Maurizio Zazzi & Monika Tschochner & Hauke Walter & Thomas Lengauer, 2010. "Only Slight Impact of Predicted Replicative Capacity for Therapy Response Prediction," PLOS ONE, Public Library of Science, vol. 5(2), pages 1-10, February.
    4. Alicia Sanchez-Gorostiaga & Djordje Bajić & Melisa L Osborne & Juan F Poyatos & Alvaro Sanchez, 2019. "High-order interactions distort the functional landscape of microbial consortia," PLOS Biology, Public Library of Science, vol. 17(12), pages 1-34, December.
    5. Krishnendu Chatterjee & Andreas Pavlogiannis & Ben Adlam & Martin A Nowak, 2014. "The Time Scale of Evolutionary Innovation," PLOS Computational Biology, Public Library of Science, vol. 10(9), pages 1-7, September.
    6. Roger D Kouyos & Gabriel E Leventhal & Trevor Hinkley & Mojgan Haddad & Jeannette M Whitcomb & Christos J Petropoulos & Sebastian Bonhoeffer, 2012. "Exploring the Complexity of the HIV-1 Fitness Landscape," PLOS Genetics, Public Library of Science, vol. 8(3), pages 1-9, March.
    7. Moritz Gerstung & Niko Beerenwinkel, 2010. "Waiting Time Models of Cancer Progression," Mathematical Population Studies, Taylor & Francis Journals, vol. 17(3), pages 115-135.
    8. Sahand Khakabimamaghani & Dujian Ding & Oliver Snow & Martin Ester, 2019. "Uncovering the subtype-specific temporal order of cancer pathway dysregulation," PLOS Computational Biology, Public Library of Science, vol. 15(11), pages 1-19, November.
    9. Gilpin, William & Feldman, Marcus W., 2019. "Cryptic selection forces and dynamic heritability in generalized phenotypic evolution," Theoretical Population Biology, Elsevier, vol. 125(C), pages 20-29.

    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:bpj:sagmbi:v:10:y:2011:i:1:n:3. 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: Peter Golla (email available below). General contact details of provider: https://www.degruyter.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.