IDEAS home Printed from https://ideas.repec.org/a/plo/pcbi00/1004856.html
   My bibliography  Save this article

Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune System

Author

Listed:
  • Yael Steuerman
  • Irit Gat-Viks

Abstract

Sequence variation can affect the physiological state of the immune system. Major experimental efforts targeted at understanding the genetic control of the abundance of immune cell subpopulations. However, these studies are typically focused on a limited number of immune cell types, mainly due to the use of relatively low throughput cell-sorting technologies. Here we present an algorithm that can reveal the genetic basis of inter-individual variation in the abundance of immune cell types using only gene expression and genotyping measurements as input. Our algorithm predicts the abundance of immune cell subpopulations based on the RNA levels of informative marker genes within a complex tissue, and then provides the genetic control on these predicted immune traits as output. A key feature of the approach is the integration of predictions from various sets of marker genes and refinement of these sets to avoid spurious signals. Our evaluation of both synthetic and real biological data shows the significant benefits of the new approach. Our method, VoCAL, is implemented in the freely available R package ComICS.Author Summary: Quantitative trait locus (QTL) studies have identified a plethora of genetic variants that lead to inter-individual variation in the abundance of immune cell subpopulations, both in normal and disease states. Cell sorting is an effective method of monitoring immune cell type quantities; however, owing to the large number of possible immune cell subsets, it can be difficult to apply this method to each cell type over multiple individuals. Recent QTL studies dealt with this difficulty by focusing on an a priori selection of one or a few cell subsets. Here we introduce VoCAL, a deconvolution-based method that utilizes transcriptome data to infer the quantities of immune cell types, and then uses these quantitative traits to uncover the underlying DNA loci. Our results in synthetic data and lung cohorts show that the VoCAL method outperforms other alternatives in revealing the genetic basis of immune physiology.

Suggested Citation

  • Yael Steuerman & Irit Gat-Viks, 2016. "Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune System," PLOS Computational Biology, Public Library of Science, vol. 12(4), pages 1-22, April.
    • Handle: RePEc:plo:pcbi00:1004856
    DOI: 10.1371/journal.pcbi.1004856
    as

    Download full text from publisher

    File URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004856
    Download Restriction: no
    File URL: https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004856&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pcbi.1004856?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. Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2010. "Regularization Paths for Generalized Linear Models via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i01).
    2. Hui Zou & Trevor Hastie, 2005. "Addendum: Regularization and variable selection via the elastic net," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 67(5), pages 768-768, November.
    3. Hui Zou & Trevor Hastie, 2005. "Regularization and variable selection via the elastic net," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 67(2), pages 301-320, April.
    4. Ting Gong & Nicole Hartmann & Isaac S Kohane & Volker Brinkmann & Frank Staedtler & Martin Letzkus & Sandrine Bongiovanni & Joseph D Szustakowski, 2011. "Optimal Deconvolution of Transcriptional Profiling Data Using Quadratic Programming with Application to Complex Clinical Blood Samples," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-11, November.
    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. Tutz, Gerhard & Pößnecker, Wolfgang & Uhlmann, Lorenz, 2015. "Variable selection in general multinomial logit models," Computational Statistics & Data Analysis, Elsevier, vol. 82(C), pages 207-222.
    2. Mkhadri, Abdallah & Ouhourane, Mohamed, 2013. "An extended variable inclusion and shrinkage algorithm for correlated variables," Computational Statistics & Data Analysis, Elsevier, vol. 57(1), pages 631-644.
    3. Susan Athey & Guido W. Imbens & Stefan Wager, 2018. "Approximate residual balancing: debiased inference of average treatment effects in high dimensions," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 80(4), pages 597-623, September.
    4. Chuliá, Helena & Garrón, Ignacio & Uribe, Jorge M., 2024. "Daily growth at risk: Financial or real drivers? The answer is not always the same," International Journal of Forecasting, Elsevier, vol. 40(2), pages 762-776.
    5. Christopher J Greenwood & George J Youssef & Primrose Letcher & Jacqui A Macdonald & Lauryn J Hagg & Ann Sanson & Jenn Mcintosh & Delyse M Hutchinson & John W Toumbourou & Matthew Fuller-Tyszkiewicz &, 2020. "A comparison of penalised regression methods for informing the selection of predictive markers," PLOS ONE, Public Library of Science, vol. 15(11), pages 1-14, November.
    6. Immanuel Bayer & Philip Groth & Sebastian Schneckener, 2013. "Prediction Errors in Learning Drug Response from Gene Expression Data – Influence of Labeling, Sample Size, and Machine Learning Algorithm," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-13, July.
    7. Mostafa Rezaei & Ivor Cribben & Michele Samorani, 2021. "A clustering-based feature selection method for automatically generated relational attributes," Annals of Operations Research, Springer, vol. 303(1), pages 233-263, August.
    8. Gustavo A. Alonso-Silverio & Víctor Francisco-García & Iris P. Guzmán-Guzmán & Elías Ventura-Molina & Antonio Alarcón-Paredes, 2021. "Toward Non-Invasive Estimation of Blood Glucose Concentration: A Comparative Performance," Mathematics, MDPI, vol. 9(20), pages 1-13, October.
    9. Christopher Kath & Florian Ziel, 2018. "The value of forecasts: Quantifying the economic gains of accurate quarter-hourly electricity price forecasts," Papers 1811.08604, arXiv.org.
    10. Karim Barigou & Stéphane Loisel & Yahia Salhi, 2020. "Parsimonious Predictive Mortality Modeling by Regularization and Cross-Validation with and without Covid-Type Effect," Risks, MDPI, vol. 9(1), pages 1-18, December.
    11. Gurgul Henryk & Machno Artur, 2017. "Trade Pattern on Warsaw Stock Exchange and Prediction of Number of Trades," Statistics in Transition New Series, Statistics Poland, vol. 18(1), pages 91-114, March.
    12. Michael Funke & Kadri Männasoo & Helery Tasane, 2023. "Regional Economic Impacts of the Øresund Cross-Border Fixed Link: Cui Bono?," CESifo Working Paper Series 10557, CESifo.
    13. Camila Epprecht & Dominique Guegan & Álvaro Veiga & Joel Correa da Rosa, 2017. "Variable selection and forecasting via automated methods for linear models: LASSO/adaLASSO and Autometrics," Post-Print halshs-00917797, HAL.
    14. Zichen Zhang & Ye Eun Bae & Jonathan R. Bradley & Lang Wu & Chong Wu, 2022. "SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Štefan Lyócsa & Petra Vašaničová & Branka Hadji Misheva & Marko Dávid Vateha, 2022. "Default or profit scoring credit systems? Evidence from European and US peer-to-peer lending markets," Financial Innovation, Springer;Southwestern University of Finance and Economics, vol. 8(1), pages 1-21, December.
    16. Peter Bühlmann & Jacopo Mandozzi, 2014. "High-dimensional variable screening and bias in subsequent inference, with an empirical comparison," Computational Statistics, Springer, vol. 29(3), pages 407-430, June.
    17. Peter Martey Addo & Dominique Guegan & Bertrand Hassani, 2018. "Credit Risk Analysis Using Machine and Deep Learning Models," Risks, MDPI, vol. 6(2), pages 1-20, April.
    18. Capanu, Marinela & Giurcanu, Mihai & Begg, Colin B. & Gönen, Mithat, 2023. "Subsampling based variable selection for generalized linear models," Computational Statistics & Data Analysis, Elsevier, vol. 184(C).
    19. Abhinav Kaushik & Diane Dunham & Xiaorui Han & Evan Do & Sandra Andorf & Sheena Gupta & Andrea Fernandes & Laurie Elizabeth Kost & Sayantani B. Sindher & Wong Yu & Mindy Tsai & Robert Tibshirani & Sco, 2022. "CD8+ T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Tomáš Plíhal, 2021. "Scheduled macroeconomic news announcements and Forex volatility forecasting," Journal of Forecasting, John Wiley & Sons, Ltd., vol. 40(8), pages 1379-1397, December.

    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:plo:pcbi00:1004856. 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: ploscompbiol (email available below). General contact details of provider: https://journals.plos.org/ploscompbiol/ .

    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.