Abstract
Independent Component Analysis (ICA) can be used to model gene expression data as an action of a set of statistically independent hidden factors. The ICA analysis with a downstream component analysis was successfully applied to transcriptomic data previously in order to decompose bulk transcriptomic data into interpretable hidden factors. Some of these factors reflect the presence of an immune infiltrate in the tumor environment. However, no foremost studies focused on reproducibility of the ICA-based immune-related signal in the tumor transcriptome. In this work, we use ICA to detect immune signals in six independent transcriptomic datasets. We observe several strongly reproducible immune-related signals when ICA is applied in sufficiently high-dimensional space (close to one hundred). Interestingly, we can interpret these signals as cell-type specific signals reflecting a presence of T-cells, B-cells and myeloid cells, which are of high interest in the field of oncoimmunology. Further quantification of these signals in tumoral transcriptomes has a therapeutic potential.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Swartz, M.A., Iida, N., Roberts, E.W., Sangaletti, S., Wong, M.H., Yull, F.E., Coussens, L.M., DeClerck, Y.A.: Tumor microenvironment complexity: emerging roles in cancer therapy (2012)
Becht, E., Giraldo, N.A., Lacroix, L., Buttard, B., Elarouci, N., Petitprez, F., Selves, J., Laurent-Puig, P., Sautès-Fridman, C., Fridman, W.H., et al.: Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 17(1), 218 (2016)
Newman, A.M., Liu, C.L., Green, M.R., Gentles, A.J., Feng, W., Xu, Y., Hoang, C.D., Diehn, M., Alizadeh, A.A.: Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12(5), 453–457 (2015)
Racle, J., de Jonge, K., Baumgaertner, P., Speiser, D.E., Gfeller, D.: Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data. eLife 6, e26476 (2017)
Roman, T., Xie, L., Schwartz, R.: Automated deconvolution of structured mixtures from heterogeneous tumor genomic data. PLoS Comput. Biol. 13(10), e1005815 (2017)
Gaujoux, R., Seoighe, C.: Semi-supervised nonnegative matrix factorization for gene expression deconvolution: a case study. Infect. Genet. Evol. 12(5), 913–921 (2012)
Brunet, J.P., Tamayo, P., Golub, T.R., Mesirov, J.P.: Metagenes and molecular pattern discovery using matrix factorization. Proc. Natl. Acad. Sci. 101(12), 4164–4169 (2004)
Hyvärinen, A., Oja, E.: Independent component analysis: algorithms and applications. Neural Netw. 13(45), 411–430 (2000)
Zinovyev, A., Kairov, U., Karpenyuk, T., Ramanculov, E.: Blind source separation methods for deconvolution of complex signals in cancer biology. Biochem. Biophys. Res. Commun. 430(3), 1182–1187 (2013)
Teschendorff, A.E., Journée, M., Absil, P.A., Sepulchre, R., Caldas, C.: Elucidating the altered transcriptional programs in breast cancer using independent component analysis. PLoS Comput. Biol. 3(8), 1539–1554 (2007)
Biton, A., Bernard-Pierrot, I., Lou, Y., Krucker, C., Chapeaublanc, E., Rubio-Pérez, C., López-Bigas, N., Kamoun, A., Neuzillet, Y., Gestraud, P., Grieco, L., Rebouissou, S., DeReyniès, A., Benhamou, S., Lebret, T., Southgate, J., Barillot, E., Allory, Y., Zinovyev, A., Radvanyi, F.: Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes. Cell Rep. 9(4), 1235–1245 (2014)
Gorban, A., Kegl, B., Wunch, D., Zinovyev, A.: Principal Manifolds for Data Visualisation and Dimension Reduction. Lecture notes in Computational Science and Engineering, vol. 58, p. 340. Springer, Heidelberg (2008)
Saidi, S.A., Holland, C.M., Kreil, D.P., MacKay, D.J.C., Charnock-Jones, D.S., Print, C.G., Smith, S.K.: Independent component analysis of microarray data in the study of endometrial cancer. Oncogene 23(39), 6677–6683 (2004)
Bang-Berthelsen, C.H., Pedersen, L., Fløyel, T., Hagedorn, P.H., Gylvin, T., Pociot, F.: Independent component and pathway-based analysis of miRNA-regulated gene expression in a model of type 1 diabetes. BMC Genomics 12, 97 (2011)
Kairov, U., Cantini, L., Greco, A., Molkenov, A., Czerwinska, U., Barillot, E., Zinovyev, A.: Determining the optimal number of independent components for reproducible transcriptomic data analysis. BMC Genomics 18(1), 712 (2017)
Weinstein, J.N., Collisson, E.A., Mills, G.B., Shaw, K.R.M., Ozenberger, B.A., Ellrott, K., Shmulevich, I., Sander, C., Stuart, J.M., Network, C.G.A.R., et al.: The cancer genome atlas pan-cancer analysis project. Nat. Genet. 45(10), 1113 (2013)
Curtis, C., Shah, S.P., Chin, S.F., Turashvili, G., Rueda, O.M., Dunning, M.J., Speed, D., Lynch, A.G., Samarajiwa, S., Yuan, Y., Gräf, S., Ha, G., Haffari, G., Bashashati, A., Russell, R., McKinney, S., Aparicio, S., Brenton, J.D., Ellis, I., Huntsman, D., Pinder, S., Murphy, L., Bardwell, H., Ding, Z., Jones, L., Liu, B., Papatheodorou, I., Sammut, S.J., Wishart, G., Chia, S., Gelmon, K., Speers, C., Watson, P., Blamey, R., Green, A., MacMillan, D., Rakha, E., Gillett, C., Grigoriadis, A., De Rinaldis, E., Tutt, A., Parisien, M., Troup, S., Chan, D., Fielding, C., Maia, A.T., McGuire, S., Osborne, M., Sayalero, S.M., Spiteri, I., Hadfield, J., Bell, L., Chow, K., Gale, N., Kovalik, M., Ng, Y., Prentice, L., Tavaré, S., Markowetz, F., Langerød, A., Provenzano, E., Purushotham, A., Børresen-Dale, A.L., Caldas, C.: The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486(7403), 346–352 (2012)
Guedj, M., Marisa, L., De Reynies, A., Orsetti, B., Schiappa, R., Bibeau, F., MacGrogan, G., Lerebours, F., Finetti, P., Longy, M., Bertheau, P., Bertrand, F., Bonnet, F., Martin, A.L., Feugeas, J.P., Bièche, I., Lehmann-Che, J., Lidereau, R., Birnbaum, D., Bertucci, F., De Thé, H., Theillet, C.: A refined molecular taxonomy of breast cancer. Oncogene 31(9), 1196–1206 (2012)
Bekhouche, I., Finetti, P., Adelaïde, J., Ferrari, A., Tarpin, C., Charafe-Jauffret, E., Charpin, C., Houvenaeghel, G., Jacquemier, J., Bidaut, G., Birnbaum, D., Viens, P., Chaffanet, M., Bertucci, F.: High-resolution comparative genomic hybridization of Inflammatory breast cancer and identification of candidate genes. PLoS ONE 6(2), e16950 (2011)
Wang, Y., Klijn, J.G., Zhang, Y., Sieuwerts, A.M., Look, M.P., Yang, F., Talantov, D., Timmermans, M., Meijer-Van Gelder, M.E., Yu, J., Jatkoe, T., Berns, E.M., Atkins, D., Foekens, J.A.: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365(9460), 671–679 (2005)
Reyal, F., Rouzier, R., Depont-Hazelzet, B., Bollet, M.A., Pierga, J.Y., Alran, S., Salmon, R.J., Fourchotte, V., Vincent-Salomon, A., Sastre-Garau, X., Antoine, M., Uzan, S., Sigal-Zafrani, B., de Rycke, Y.: The molecular subtype classification is a determinant of sentinel node positivity in early breast carcinoma. PLoS ONE 6(5), e20297 (2011)
Himberg, J., Hyvärinen, A.: ICASSO: software for investigating the reliability of ICA estimates by clustering and visualization. In: Neural Networks for Signal Processing - Proceedings of the IEEE Workshop, vol. 2003, pp. 259–268, January 2003
Cantini, L., Calzone, L., Martignetti, L., Rydenfelt, M., Blüthgen, N., Barillot, E., Zinovyev, A.: Classification of gene signatures for their information value and functional redundancy. npj Syst. Biol. Appl. 4(1), 2 (2018)
Wickham, H.: ggplot2 Elegant Graphics for Data Analysis, vol. 35 (2009)
Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Schwikowski, B., Ideker, T.: Cytoscape: a software Environment for integrated models of biomolecular interaction networks. Genome Res. 13(11), 2498–2504 (2003)
Shay, T., Kang, J.: Immunological Genome Project and systems immunology (2013)
Kerdiles, Y.M., Almeida, F.F., Thompson, T., Chopin, M., Vienne, M., Bruhns, P., Huntington, N.D., Raulet, D.H., Nutt, S.L., Belz, G.T., Vivier, E.: Natural-Killer-like B cells display the phenotypic and functional characteristics of conventional B cells. Immunity 47(2), 199–200 (2017)
Schelker, M., Feau, S., Du, J., Ranu, N., Klipp, E., MacBeath, G., Schoeberl, B., Raue, A.: Estimation of immune cell content in tumour tissue using single-cell RNA-seq data. Nature Commun. 8(1), 2032 (2017)
Acknowledgments
We thank Vassili Soumelis for discussions on multidimensionality of biological systems. This work has been funded by INSERM Plan Cancer \(\mathrm {N}\) BIO2014-08 COMET grant under ITMO Cancer BioSys program and by ITMO Cancer (AVIESAN) who provided 3-year PhD grant. We would like to acknowledge as well foundation Bettencourt Schueller and Center for Interdisciplinary Research funding for the training of the PhD student.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this paper
Cite this paper
Czerwinska, U., Cantini, L., Kairov, U., Barillot, E., Zinovyev, A. (2018). Application of Independent Component Analysis to Tumor Transcriptomes Reveals Specific and Reproducible Immune-Related Signals. In: Deville, Y., Gannot, S., Mason, R., Plumbley, M., Ward, D. (eds) Latent Variable Analysis and Signal Separation. LVA/ICA 2018. Lecture Notes in Computer Science(), vol 10891. Springer, Cham. https://doi.org/10.1007/978-3-319-93764-9_46
Download citation
DOI: https://doi.org/10.1007/978-3-319-93764-9_46
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-93763-2
Online ISBN: 978-3-319-93764-9
eBook Packages: Computer ScienceComputer Science (R0)