IDEAS home Printed from https://ideas.repec.org/a/plo/pcbi00/1006976.html
   My bibliography  Save this article

Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares

Author

Listed:
  • Yuning Hao
  • Ming Yan
  • Blake R Heath
  • Yu L Lei
  • Yuying Xie

Abstract

Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. We developed a new machine learning tool, Fast And Robust DEconvolution of Expression Profiles (FARDEEP), to enumerate immune cell subsets from whole tumor tissue samples. To reduce noise in the tumor gene expression datasets, FARDEEP utilizes an adaptive least trimmed square to automatically detect and remove outliers before estimating the cell compositions. We show that FARDEEP is less susceptible to outliers and returns a better estimation of coefficients than the existing methods with both numerical simulations and real datasets. FARDEEP provides an estimate related to the absolute quantity of each immune cell subset in addition to relative percentages. Hence, FARDEEP represents a novel robust algorithm to complement the existing toolkit for the characterization of tissue-infiltrating immune cell landscape. The source code for FARDEEP is implemented in R and available for download at https://github.com/YuningHao/FARDEEP.git.Author summary: Rapidly emerging evidence suggests that the tumor immune microenvironment not only predisposes cancer patients to diverse treatment outcomes but also represents a promising source of biomarkers for better patient stratification. Different from the immunohistochemistry-based scoring practice, which focuses on a few selected marker proteins, immune deconvolution pipelines inform a previously untapped method to comprehensively reveal the tumor-infiltrating immune landscape. Recognizing the numerous strengths of existing immune deconvolution algorithms, here we show data outliers, which are inevitable in whole tissue sequencing data sets, substantially skew estimation results. Moreover, an estimate related to the absolute amount of each immune subset offers valuable insight into the nature of the host response in addition to percentage information alone. Thus, we engineered a new immune deconvolution pipeline, coined as Fast and Robust Deconvolution of Expression Profiles (FARDEEP), to automatically detect and remove outliers prior feeding data into the deconvolution algorithm and to provide estimates related to the absolute quantity of each immune subset. Utilizing both synthetic and real data sets, we found that FARDEEP returns superior coefficients and offers a robust tool to reveal the immune landscape of human cancers.

Suggested Citation

  • Yuning Hao & Ming Yan & Blake R Heath & Yu L Lei & Yuying Xie, 2019. "Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares," PLOS Computational Biology, Public Library of Science, vol. 15(5), pages 1-21, May.
  • Handle: RePEc:plo:pcbi00:1006976
    DOI: 10.1371/journal.pcbi.1006976
    as

    Download full text from publisher

    File URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006976
    Download Restriction: no

    File URL: https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006976&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pcbi.1006976?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. She, Yiyuan & Owen, Art B., 2011. "Outlier Detection Using Nonconvex Penalized Regression," Journal of the American Statistical Association, American Statistical Association, vol. 106(494), pages 626-639.
    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.
    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. Umberto Amato & Anestis Antoniadis & Italia De Feis & Irene Gijbels, 2021. "Penalised robust estimators for sparse and high-dimensional linear models," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 30(1), pages 1-48, March.
    2. Wentao Qu & Xianchao Xiu & Huangyue Chen & Lingchen Kong, 2023. "A Survey on High-Dimensional Subspace Clustering," Mathematics, MDPI, vol. 11(2), pages 1-39, January.
    3. Luca Insolia & Ana Kenney & Martina Calovi & Francesca Chiaromonte, 2021. "Robust Variable Selection with Optimality Guarantees for High-Dimensional Logistic Regression," Stats, MDPI, vol. 4(3), pages 1-17, August.
    4. Mishra, Aditya & Müller, Christian L., 2022. "Robust regression with compositional covariates," Computational Statistics & Data Analysis, Elsevier, vol. 165(C).
    5. She, Yiyuan, 2012. "An iterative algorithm for fitting nonconvex penalized generalized linear models with grouped predictors," Computational Statistics & Data Analysis, Elsevier, vol. 56(10), pages 2976-2990.
    6. Kepplinger, David, 2023. "Robust variable selection and estimation via adaptive elastic net S-estimators for linear regression," Computational Statistics & Data Analysis, Elsevier, vol. 183(C).
    7. 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.
    8. Oxana Babecka Kucharcukova & Jan Bruha, 2016. "Nowcasting the Czech Trade Balance," Working Papers 2016/11, Czech National Bank.
    9. Carstensen, Kai & Heinrich, Markus & Reif, Magnus & Wolters, Maik H., 2020. "Predicting ordinary and severe recessions with a three-state Markov-switching dynamic factor model," International Journal of Forecasting, Elsevier, vol. 36(3), pages 829-850.
    10. Hou-Tai Chang & Ping-Huai Wang & Wei-Fang Chen & Chen-Ju Lin, 2022. "Risk Assessment of Early Lung Cancer with LDCT and Health Examinations," IJERPH, MDPI, vol. 19(8), pages 1-12, April.
    11. Margherita Giuzio, 2017. "Genetic algorithm versus classical methods in sparse index tracking," Decisions in Economics and Finance, Springer;Associazione per la Matematica, vol. 40(1), pages 243-256, November.
    12. Nicolaj N. Mühlbach, 2020. "Tree-based Synthetic Control Methods: Consequences of moving the US Embassy," CREATES Research Papers 2020-04, Department of Economics and Business Economics, Aarhus University.
    13. Wang, Qiao & Zhou, Wei & Cheng, Yonggang & Ma, Gang & Chang, Xiaolin & Miao, Yu & Chen, E, 2018. "Regularized moving least-square method and regularized improved interpolating moving least-square method with nonsingular moment matrices," Applied Mathematics and Computation, Elsevier, vol. 325(C), pages 120-145.
    14. Dmitriy Drusvyatskiy & Adrian S. Lewis, 2018. "Error Bounds, Quadratic Growth, and Linear Convergence of Proximal Methods," Mathematics of Operations Research, INFORMS, vol. 43(3), pages 919-948, August.
    15. 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.
    16. Lucian Belascu & Alexandra Horobet & Georgiana Vrinceanu & Consuela Popescu, 2021. "Performance Dissimilarities in European Union Manufacturing: The Effect of Ownership and Technological Intensity," Sustainability, MDPI, vol. 13(18), pages 1-19, September.
    17. Candelon, B. & Hurlin, C. & Tokpavi, S., 2012. "Sampling error and double shrinkage estimation of minimum variance portfolios," Journal of Empirical Finance, Elsevier, vol. 19(4), pages 511-527.
    18. 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.
    19. Andrea Carriero & Todd E. Clark & Massimiliano Marcellino, 2025. "Specification Choices in Quantile Regression for Empirical Macroeconomics," Journal of Applied Econometrics, John Wiley & Sons, Ltd., vol. 40(1), pages 57-73, January.
    20. Kim, Hyun Hak & Swanson, Norman R., 2018. "Mining big data using parsimonious factor, machine learning, variable selection and shrinkage methods," International Journal of Forecasting, Elsevier, vol. 34(2), pages 339-354.

    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:pcbi00:1006976. 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.