Penalized inference of the hematopoietic cell differentiation network via high-dimensional clonal tracking
Tóm tắt
During their lifespan, stem- or progenitor cells have the ability to differentiate into more committed cell lineages. Understanding this process can be key in treating certain diseases. However, up until now only limited information about the cell differentiation process is known. The goal of this paper is to present a statistical framework able to describe the cell differentiation process at the single clone level and to provide a corresponding inferential procedure for parameters estimation and structure reconstruction of the differentiation network. We propose a multidimensional, continuous-time Markov model with density-dependent transition probabilities linear in sub-population sizes and rates. The inferential procedure is based on an iterative calculation of approximated solutions for two systems of ordinary differential equations, describing process moments evolution over time, that are analytically derived from the process’ master equation. Network sparsity is induced by adding a SCAD-based penalization term in the generalized least squares objective function. The methods proposed here have been tested by means of a simulation study and then applied to a data set derived from a gene therapy clinical trial, in order to investigate hematopoiesis in humans, in-vivo. The hematopoietic structure estimated contradicts the classical dichotomy theory of cell differentiation and supports a novel myeloid-based model recently proposed in the literature.
Tài liệu tham khảo
Abkowitz, JL, Linenberger ML, Newton MA, Shelton GH, Ott RL, Guttorp P (1990) Evidence for the maintenance of hematopoiesis in a large animal by the sequential activation of stem-cell clones. Proc Natl Acad Sci 87(22):9062–9066.
Aiuti, A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee PP, Orange JS, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, Naldini L (2013) Lentiviral hematopoietic stem cell gene therapy in patients with wiskott-aldrich syndrome. Science 341(6148). https://doi.org/10.1126/science.1233151. http://arxiv.org/abs/http://www.sciencemag.org/content/341/6148/1233151.full.pdf.
Ambrosi, A, Cattoglio C, Di Serio C (2008) Retroviral integration process in the human genome: is it really non-random? a new statistical approach. PLoS Comput Biol 4(8):1000144.
Bates, D, Maechler M (2015) Matrix: Sparse and Dense Matrix Classes and Methods. R package version 1.2-2. http://CRAN.R-project.org/package=Matrix. Accessed 25 Oct 2019.
Biasco, L, Ambrosi A, Pellin D, Bartholomae C, Brigida I, Roncarolo MG, Di Serio C, von Kalle C, Schmidt M, Aiuti A (2011) Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell. EMBO Mol Med 2(5):1757–4684.
Becker, A, McCulloch E, Till J (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454.
Biasco, L, Pellin D, Scala S, Dionisio F, Basso-Ricci L, Leonardelli L, Scaramuzza S, Baricordi C, Ferrua F, Cicalese MP, et al. (2016) In vivo tracking of human hematopoiesis reveals patterns of clonal dynamics during early and steady-state reconstitution phases. Cell Stem Cell 19:107–119.
Catlin, SN, Abkowitz JL, Guttorp P (2001) Statistical inference in a two-compartment model for hematopoiesis. Biometrics 57(2):546–553.
Fan, J (1997) Comments on wavelets in statistics: a reviews by a. antoniadis. J Ital Stat Assoc 6:131–138.
Fan, J, Li R (2001) Variable selection via nonconcave penalized likelihood and its oracle properties. J Am Stat Assoc 96:1348–1360.
Gardiner, CW (1985) Handbook of Stochastic Methods. Springer, New York.
Gillespie, DT (1977) Exact stochastic simulation of coupled chemical reactions. J Phys Chem 81(25):2340–2361.
Golub, GH, Heath M, Wahba G (1979) Generalized cross-validation as a method for choosing a good ridge parameter. Technometrics 21(2):215–223.
Goyal, S, Kim S, Chen IS, Chou T (2015) Mechanisms of blood homeostasis: lineage tracking and a neutral model of cell populations in rhesus macaques. BMC Biol 13(1):85.
Guennebaud, G, Jacob B, et al. (2010) Eigen v3. http://eigen.tuxfamily.org. Accessed 25 Oct 2019.
IBM (2010) Userś Manual for CPLEX. IBM ILOG CPLEX V12.1. https://public.dhe.ibm.com/software/websphere/ilog/docs/optimization/cplex/ps_usrmancplex.pdf. Accessed 25 Oct 2019.
Kampen, NGV (1981) Stochastic Processes in Physics and Chemistry. North-Holland, Amsterdam.
Kawamoto, H, Ikawa T, Masuda K, Wada H, Katsura Y (2010) A map for lineage restriction of progenitors during hematopoiesis: the essence of the myeloid-based model. Immunol Rev 238(1):23–36.
Kawamoto, H, Wada H, Katsura Y (2010) A revised scheme for developmental pathways of hematopoietic cells: the myeloid-based model. Int Immunol 22(2):65–70.
Marciniak-Czochra, A, Stiehl T (2013) Mathematical models of hematopoietic reconstitution after stem cell transplantation In: Model Based Parameter Estimation, 191–206.. Springer, Berlin.
Naldini, L (2011) Ex vivo gene transfer and correction for cell-based therapies. Nat Rev Genet 12(5):301–15.
Pellin, D, Di Serio C (2016) A novel scan statistics approach for clustering identification and comparison in binary genomic data. BMC Bioinformatics 17(11):320.
Purutcuoglu, V, Wit E (2008) Bayesian inference for the mapk erk pathway by considering the dependency of the kinetic parameters. Bayesian Anal 3(4):851–886.
R Core Team (2015) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna. R Foundation for Statistical Computing. https://www.R-project.org/. Accessed 25 Oct 2019.
Risken, H (1984) The Fokker-Planck Equation. Springer, New York.
Romano, O, Peano C, Tagliazucchi GM, Petiti L, Poletti V, Cocchiarella F, Rizzi E, Severgnini M, Cavazza A, Rossi C, et al (2016) Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment. Sci Rep 6:24724.
Rousseeuw, PJ, Croux C (1993) Alternatives to the median absolute deviation. J Am Stat Assoc 88(424):1273–1283.
Scala, S, Basso-Ricci L, Dionisio F, Pellin D, Giannelli S, Salerio FA, Leonardelli L, Cicalese MP, Ferrua F, Aiuti A, et al (2018) Dynamics of genetically engineered hematopoietic stem and progenitor cells after autologous transplantation in humans. Nat Med 24(11):1683.
Stroustrup, B (1997) The C++ Programming Language. 3rd edn. Addison-Wesley, Boston.
Tibshirany, R (1996) Regression shrinkage and selection via the lasso. J R Stat Soc Ser B 58:267–288.
Wilkinson, DJ (2006) Stochastic Modelling for Systems Biology. Chapman and Hall, London.