Vincent Detours

Computational Biology Group – IRIBHM Jacques E. Dumont – ULB

Research

Thyroid cancer

Our group has profiled the transcriptomes of most thyroid neoplasms, including a recent single nuclei and spatial transcriptomics of papillary and anaplastic thyroid cancer. Current projects include:

  • 3D thyroid histology. What makes a normal thyroid follicular cell cancerous? What specific genomic events or microanatomical changes are necessary and sufficient to set a normal cell on the path to cancer? To better understand the initiation and development of thyroid cancer, one must first study somatic mutations in the histological context of the histologically normal thyroid, then in cancer. This basic research proposal aims at filling this gap by combining the 3D reconstruction of normal and papillary thyroid cancer (PTC) histologies at cellular resolution over cm3 volumes—positions of billions of cells will be determined—with spatially resolved DNA and mRNA profiling of the same samples.
  • Clonal expansion of thyroid parenchymal and mesenchymal cells during thyroid development and cancer progression. This is a collaborative project with the groups of Sabine Costagliola, Mirian Romitti and Maxime Tarabichi at IRIBHM – Jacques E. Dumont. Evidence to date suggests that the embryonic development of the thyroid gland is dependent on the interplay between transcription factors HHEX, NKX-2.1, PAX8 and FOXE1, but is also orchestrated by extrinsic factors such as BMP, FGF, WNT that are secreted by cells supporting the differentiating parenchyma. In a subset of aggressive papillary thyroid cancers (PTC), dedifferentiation and tumoral expansion are associated with stromal fibroblasts proliferation. Thanks to our recently developed in-house human thyroid organoid model, we investigate the interplay of parenchymal and mesenchymal cells during development and cancer progression with assay combining mRNA phenotyping and lineage tracing.

Quantitative pathology atlases

Histology started with the invention of the microscope in the XVIIth century. It yielded fundamental discoveries such as the cellular basis of life. Yet, while microscope technology has massively improved since then, the form of histological structures description has barely evolved across the centuries: it rests on natural language statements that are qualitative and somewhat subjective. As a result, many differential diagnostics tasks in histo-pathology are notoriously unreliable. In addition, researchers lack a principled quantitative and objective framework to properly investigate histological images.

Our group is developed an artificial intelligence-based pipeline that sets histology of a firm quantitative ground. Given a large collection of whole slide images (WSI) it generates an atlas of the morphologies they contain and the quantifications of each morphology in each WSI. Importantly, this pipeline is unsupervised and free of human biases.

Human sexual dimorphism

Sexual dimorphism (SD)—sexual differences beyond genitals—is as widespread as it is diverse across the animal kingdom. Human dimorphic traits include body composition, body size and proportions, breast size, physiology, voice pitch, behavior, etc. Culture is a major force determining contemporary human experience and behavior which may measurably affect SD and certainly shapes its societal perception and scientific observation.

The binary definition of sex has been challenged over the last thirty years. The debate has permeated the mass media. Its impact is clearly being felt, including by a rising number of individuals considering sex change. Beyond socio-cultural aspects, any progress on SD will impact research on the many sex-biased diseases. Nevertheless, much remain to be discovered about SD in most internal organs and across the layers of biological complexity. To the best of our knowledge, no unified quantitative approach to SD has been proposed so far.

We are developing a quantitative measure of SD. It is computable on any high dimensional data which enables it to integrate complex phenotypes, thus avoids any a priori bias about which traits are, or are not, dimorphic.

Group members

Head: Vincent Detours

Postdoc: Valeriia Guiala

PhD students:

  • Oier Azurmendi Senar (co-supervision with Jean-Luc Van Laethem)
  • Hugo Mantion
  • Diego Serra
  • Zhao Zhang

Publications

  1. Tourneur A., Rodrigues Vitória J., Saiselet M., Craciun L., Larsimont D., Lefort A., Libert F., Maenhaut C., Costagliola S., Tarabichi M., Romitti M., Detours V., (2024), Single nuclei and spatial transcriptomes suggest a stratification of papillary and anaplastic thyroid cancer cells, BioRxiv, 10.1101/2024.02.15.580495
  2. Quiriny M., Rodrigues VitÏŒria J., Saiselet M., Dom G., De Saint Aubain N., Willemse E., Digonnet A., Dequanter D., Rodriguez A., Andry G., Detours V., Maenhaut C., (2024), Description of a New miRNA Signature for the Surgical Management of Thyroid Nodules, Cancers (Basel) 16(24):4214. doi: 10.3390/cancers16244214
  3. Lasolle H., Schiavo A., Tourneur A., Gillotay P., de Faria da Fonseca B., Ceolin L, Monestier O., Aganahi B., Chomette L., Kizys M.M.L., Haenebalcke L., Pieters T., Goossens S., Haigh J., Detours V., Maia A.L.S., Costagliola S., Romitti M., (2024), Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids, Oncogene, 43(3):155-170.
  4. Romitti M., Tourneur A., de Faria da Fonseca B., Doumont G., Gillotay P., Liao X.H., Eski S.E., Van Simaeys G., Chomette L., Lasolle H., Monestier O., Kasprzyk DF, Detours V., Singh S.P., Goldman S., Refetoff S., Costagliola S., (2022), Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism, Nat Commun. 13(1):7057. doi: 10.1038/s41467-022-34776-7.
  5. Tarabichi M., Demetter P., Craciun L., Maenhaut C., Detours V., (2021), Thyroid cancer under the scope of emerging technologies. Mol Cell Endocrinol 541:111491. doi: 10.1016/j.mce.2021.111491.
  6. Boisson A., Noël G., Saiselet M., Rodrigues-Vitória J., Thomas N., Fontsa M.L., Sofronii D., Naveaux C., Duvillier H., Craciun L., Larsimont D., Awada A., Detours V., Willard-Gallo K., Garaud S., (2021). Fluorescent Multiplex Immunohistochemistry Coupled With Other State-Of-The-Art Techniques to Systematically Characterize the Tumor Immune Microenvironment, Front Mol Biosci 8:673042. doi: 10.3389/fmolb.2021.673042.
  7. Gillotay P., Shankar M., Haerlingen B., Sema E., Pozo-Morales M., Garteizgogeascoa I., Reinhardt S., Kränkel A., Bläsche J., Petzold A., Ninov N., Kesavan G., Lange C., Brand M., Lefort A., Libert F., Detours V., Costagliola S., Singh Pal S., (2020), Single-cell transcriptome analysis reveals thyrocyte diversity in the zebrafish thyroid gland. EMBO Rep. Dec 3;21(12):e50612, 10.15252/embr.202050612.
  8. Saiselet M., Rodrigues-Vitória J., Tourneur A., Craciun L., Spinette A., Larsimont D., Andry G., Lundeberg J., Maenhaut C., Detours V., (2020), Transcriptional output, cell types densities and normalization in spatial transcriptomics, Mol. Cell Biol., doi: 10.1093/jmcb/mjaa028
  9. Kyrilli A., Gacquer D., Detours V., Lefort A., Libert F., Twyffels L., Van den Eeckhaute L., Strickaert A., Maenhaut C., De Deken X., Dumont J.E., Miot F., Corvilain B., (2019), Dissecting the role of thyrotropin in the DNA damage response in human thyrocytes after 131I, γ-radiation and H2O2, Clin. Endocrinol. Metab., 10.1210/clinem/dgz185.
  10. Solinas C., Marcoux D., Garaud S., Vitória J.R., Van den Eynden G., de Wind A., De Silva P., Boisson A., Craciun L., Larsimont D., Piccart-Gebhart M., Detours V., t’Kint de Roodenbeke D., Willard-Gallo K. (2019), BRCA gene mutations do not shape the extent and organization of tumor infiltrating lymphocytes in triple negative breast cancer. Cancer Lett. 450:88-97, 10.1016/j.canlet.2019.02.027
  11. Ghaddhab C, Kyrilli A, Driessens N, Van Den Eeckhaute E, Hancisse O, De Deken X, Dumont JE, Detours V, Miot F, Corvilain B. (2019), Factors contributing to the resistance of the thyrocyte to hydrogen peroxide, Mol Cell Endocrinol., 481:62-70, doi: 10.1016/j.mce.2018.11.010
  12. Suzuki I.K., Gacquer D., Van Heurck R., Kumar D., Wojno M., Bilheu A., Herpoel A., Lambert N., Chéron J., Polleux F., Detours V., Vanderhaeghen P., (2018), Human-specific NOTCH2 paralogs expand human cortical neurogenesis through regulation of Delta/Notch interactions. Cell 31;173(6):1370-1384, doi: 10.1016/j.cell.2018.03.067. [Comments on this paper by E. Pennisi Science (2018) doi: 10.1126/science.360.6392.951; Nature May 31st 2018; A. Onela, The Scientist May 31st 2018; etc. News media coverage: New York Times, The Economist, Spiegle, Le Soir, Het Last Neuws, VRT, etc.]
  13. Fimereli D., Fumagalli D., Brown D., Gacquer D., Rothé F., Salgado R., Larsimont D., Sotiriou C., Detours V., (2018), Genomic hotspots but few recurrent fusion genes in breast cancer. Genes Chromosomes Cancer. doi: 10.1002/gcc.22533.
  14. Tarabichi M., Antoniou A., Le Pennec S., Gacquer D., de Saint Aubain N., Craciun L., Cielen T., Laios I., Larsimont D., Andry G., Dumont J.E., Maenhaut C., Detours V., (2018), Distinctive desmoplastic 3D morphology associated with BRAFV600E in papillary thyroid cancers, J Clin Endocrinol Metab. doi:10.1210/jc.2017-02279.
  15. Solinas C., Garaud S., De Silva P., Boisson A., Van den Eynden G., de Wind A., Risso P., Rodrigues Vitória J., Richard F., Migliori E., Noël G., Duvillier H., Craciun L., Veys I., Awada A., Detours V. Larsimont D., Piccart-Gebhart M., Willard-Gallo K., (2017), Immune Checkpoint Molecules on Tumor-Infiltrating Lymphocytes and Their Association with Tertiary Lymphoid Structures in Human Breast Cancer. Front Immunol., doi:10.3389/fimmu.2017.01412.
  16. Tarabichi M. & Detours V. (2016), A research note regarding “Variation in cancer risk among tissues can be explained by the number of stem cell divisions”, F1000 Research, doi:10.12688/f1000research.9448.1
  17. Saiselet M., Pita J.M., Augenlicht A., Dom G., Tarabichi M., Fimereli D., Dumont JE., Detours V., Maenhaut C. (2016), miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers, Oncotarget, doi: 10.18632/oncotarget.9655.
  18. Handkiewicz-Junak D., Swierniak M., Rusinek D., Oczko-Wojciechowska M., Dom G., Maenhaut C., Unger K., Detours V., Bogdanova T., Thomas G., Likhtarov I., Jaksik R., Kowalska M., Chmielik E., Jarzab M., Swierniak A. & Jarzab B., (2016), Gene signature of the post-Chernobyl papillary thyroid cancer, Eur J Nucl Med Mol Imaging, 2016 Jan 26.
  19. Saiselet M., Gacquer D., Spinette A., Craciun L., Decaussin-Petrucci M., Andry G., Detours# & Maenhaut# C., (2015), New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer, BMC Genomics,16:828. doi: 10.1186/s12864-015-2082-3
  20. Fumagalli F., Gacquer D. Rothé F, Lefort A., Libert F., Brown D., Kheddoumi N., Shlien A., Konopka, T, Salgado R., Larsimont D., Polyak K., Willard-Gallo K., Desmedt C., Piccart M., Abramowicz M., Campbell P.J., Sotiriou S. & Detours V., (2015), Principles Governing A-to-I RNA Editing in the Breast Cancer Transcriptome, Cell Reports, doi:10.1016/j.celrep.2015.09.032. [Comments on this paper by L. Shipman, Rev. Cancer (2015), doi:10.1038/nrc4044 ; Rayon-Estrada et al., Trends in Cancer (2015), doi:10.1016/j.trecan.2015.10.008]
  21. Tarabichi M., Saiselet M., Trésallet C., Hoang C., Larsimont D., Andry G., Maenhaut C. & Detours V., Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer, (2015), Br J Cancer. 112(10):1665-1674.
  22. Fimereli D., Gacquer D., Fumagalli D., Salgado R., Rothé F., Larsimont D., Sotiriou C. & Detours V., (2015), No significant viral transcription detected in whole breast cancer transcriptomes, BMC Cancer 15(1):1176.
  23. Le Pennec S., Konopka T., Gacquer D., Fimereli D., Tarabichi M., Tomás G., Savagner F., Decaussin-Petrucci M., Trésallet C., Andry G., Larsimont D., Detours# & Maenhaut# C., (2015), Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases, Endocr. Relat. Cancer 22(2):205-16.
  24. Fumagalli D., Blanchet-Cohen A., Brown D., Desmedt C., Gacquer D., Michiels S., Rothé F., Majjaj S., Salgado R., Larsimont D., Ignatiadis M., Maetens M., Piccart M. & Detours V., Sotiriou C., Haibe-Kains B., (2014), Transfer of clinically relevant gene expression signatures in breast cancer: from Affymetrix microarray to Illumina RNA-Sequencing technology, BMC Genomics 21;15(1):1008
  25. Versteyhe, Driessens N., Ghaddhab C., Tarabichi M., Hoste C., Dumont J.E., Miot F., Corvilain B. & Detours V., (2013), Comparative analysis of the thyrocytes and T-cells responses to H2O2 and radiation reveals an H2O2-induced antioxidant transcriptional program in thyrocytes, J. Clin. Endocrin. Metab., doi:10.1210/jc.2013-1266.
  26. Tarabichi M., Antoniou A., Saiselet M., Pita J.M., Andry G., Dumont J.E., Detours V. & Maenhaut C., (2013), Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and “swarm intelligence”. Cancer Metastasis Rev. 32(3-4):403-21. doi: 10.1007/s10555-013-9431-y
  27. Fimereli D., Detours V.# & Konopka T., (2013), TriageTools: tools for partitioning and prioritizing analysis of high-throughput sequencing data. Nucleic Acids Res., 41(7):e86. doi: 10.1093/nar/gkt094.
  28. Tarabichi M., Detours V.# & Konopka T., (2012), Piecewise polynomial representations of genomic tracks. PLoS One, 7(11):e48941.
  29. Coletta A., Molter C., Duque R., Steenhoff D., Taminau J., de Schaetzen V., Meganck S., Lazar C., Venet D., Detours V., Nowe A., Bersini H. & Weiss Solis D.Y., (2012), InSilico DB genomic datasets hub: an efficient starting point for analyzing genome-wide studies in GenePattern, Integrative Genomics Viewer, and R/Bioconductor, Genome Biol. 13(11) R104.
  30. Venet D., Detours V. & Bersini H., (2012). A Measure of the Signal-to-Noise Ratio of Microarray, Samples and Studies Using Gene Correlations. PLoS One 7(12): e51013.
  31. Dom G., Tarabichi M., Unger K., Thomas G., Oczko-Wojciechowska M., Bogdanova T., Jarzab B., Dumont J.E., Detours V. & Maenhaut C., (2012), A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas. J. Cancer, doi:10.1038/bjc.2012.302.
  32. Tomás G., Tarabichi M., Gacquer D., Hébrant A., Dom G., Dumont J.E., Keutgen X., Fahey T.J. 3rd, Maenhaut C. & Detours V., (2012), A general method to derive robust organ-specific gene expression-based differentiation indices: application to thyroid cancer diagnostic, Oncogene, Jan 23. doi:10.1038/onc.2011.626.
  33. Detours V., (2011), Confounded Cancer Markers, The Scientist, December 7th
  34. Venet D., Dumont J.E. & Detours V., (2011), Most Random Gene Expression Signatures are Significantly Associated with Breast Cancer Outcome, PLoS Computational Biology 7(10), e1002240. [Comments on this paper by Ng et al. (2012), Breast Cancer Res. 14, p313-5 and Jordan B. (2012) Bioassay 34(9), p730-3].
  35. Lambert N., Lambot M.A., Bilheu A., Albert V., Englert Y., Libert F., Noel J.C., Sotiriou C., Holloway A.K., Pollard K.S., Detours V. & Vanderhaeghen P. (2011), Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of evolution, PLoS One 6(3), e17753.
  36. Maenhaut C., Detours V., Dom G., Handkiewicz-Junak D., Oczko-Wojciechowska M. & Jarzab B. (2011), Gene Expression Profiles of Radiation-induced Thyroid Cancers, Oncol. 23(4), p282-8.
  37. van Staveren*, C.G., Weiss Solís*, D.Y., Hébrant, A., Detours, V., Dumont, J.E. & Maenhaut, C., (2009), Human cancer cell lines: Experimental models for cancer cells in situ? For cancer stem cells? BBA Cancer 1795(2), 92-103.
  38. Detours, V., Versteyhe, S., Dumont J. E. & Maenhaut C., (2008), Gene Expression Profiles of Post-Chernobyl Thyroid Cancers, Op. in Endocrinol., Metabolism and Diabetes 15, p440-5.
  39. Burniat, A., Jin, L., Detours, V., Driessens, N., Goffard, J.C., Santoro, M., Rothstein, J., Dumont, J.E., Miot, F. & Corvilain B., (2008), Gene Expression in RET/PTC3 and E7 Transgenic Mouse Thyroids: RET/PTC3 but not E7 Tumors are Partial and Transient Models of Human Papillary Thyroid Cancers. Endocrinology 149, p5107-17.
  40. Detours, V., Delys, L., Libert, F., Weiss Solís, D., Bogdanova, T., Dumont, J. E., Franc, B., Thomas, G. & Maenhaut, C., (2007), Genome-wide Gene Expression Profiling Suggests Distinct Radiation Susceptibilities in Sporadic and Post-Chernobyl Papillary Thyroid Cancers, British J. Cancer 97, 818-25.
  41. van Staveren* W.C., Weiss Solís* D.Y., Delys L., Duprez L., Andry G., Franc B., Thomas G., Libert F., Dumont J.E., Detours V., Maenhaut C., (2007), Human thyroid tumor cell lines derived from different tumor types present a common dedifferentiated phenotype, Cancer Res. 67(17):8113-20.
  42. Delys*, L., Detours*, V., Franc, B., Thomas, G., Bogdanova, Tronko, M., T., Libert, F., Dumont, J. E.  & Maenhaut, C., (2007), Gene expression and the biological phenotype of papillary thyroid carcinomas, Oncogene 26(57), 7894-903.
  43. Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE, (2007), Roles of hydrogen peroxide in thyroid physiology and disease, J Clin Endocrinol Metab. 92(10), 3764-73.
  44. van Staveren, C. G., Detours, V., Dumont, J. E., & Maenhaut, C., (2006), Negative feedbacks in normal cell growth and their suppression in tumorigenesis. Cell Cycle 5, 571-572.
  45. van Staveren, C. G., Weiss, D., Delys, L., Venet, D., Cappello, M., Andry, G., Dumont, J. E., Libert, F., Detours, V., & Maenhaut, C., (2006), Gene Expression in TSH-treated Human Thyrocytes and Autonomous Adenomas: Suppression of Negative Feedbacks in Tumorigenesis, Nat. Acad. Sci. USA 103, 413–418.
  46. Detours, V., Dumont, J. E., & Maenhaut, C., (2006), Systems Biology, Cell Specificity and Physiology, in Theories in Medicine, Paton R. & McNamara L. Eds. Elsevier.
  47. Wattel, S., Mircescu, H., Venet, D., Burniat, A., Franc, B., Frank, S., Andry, G., Van Sande, J., Rocmans, P., Dumont, J. E., Detours, V. & Maenhaut, C., (2005), Gene Expression in Thyroid Autonomous Adenomas Provides Insight on their Physiopathology, Oncogene 24, 6902-16.
  48. Detours, V., Wattel, S., Venet, D., Hutsebaut, N., Bogdanova, T., Tronko, M. D., Dumont, J. E., Franc, B., Thomas, G. & Maenhaut, C., (2005), Absence of a Specific Radiation Signature in Post-Chernobyl Thyroid Cancers, British J. Cancer 92, 1545-1552.
  49. Detours, V., Dumont, J. E., Bersini, H., & Maenhaut, C., (2003). Integration and Cross-Validation of High-Throughput Gene Expression Data: Comparing Heterogenous Data Sets, FEBS Lett. 546, 98-102.
  50. Yusim, K., Kesmir, C., Addo, M. M., Altfeld, M., Gaschen, B., Chigaev, A., Detours, V. & Korber, B. T., (2002), Clustering Patterns of CTL Epitopes in HIV-1 Proteins Reveal Imprints of Immune Evasion on HIV-1 Global Variation, Virology, 76(17), 8757-8768.
  51. Kesmir, C. Nussbaum, N. K., Shild, H., Detours, V., Brunak, S., (2002), Prediction of Proteasome Clivage Motifs by Neural Networks, Protein Engeneering, 15(4), 287-296.
  52. Korber, B. T., Gaschen, B., Yusim, K., Thakallapally, R., Kesmir, C. & Detours, V., (2001), Evolutionary and Immunological Implications of Contemporary HIV-1 Variation, Med. Bull., 58, 19-42.
  53. Detours, V. & Perelson, A. S., (2000), The Paradox of Alloreactivity and Self MHC Restriction: Quantitative Analysis and Statistics, Nat. Acad. Sci. USA, 97, 8479-8483.
  54. Detours, V., Mehr, R., & Perelson, A. S., (2000), Deriving Quantitative Constraints Under Which T Cell Selection Operates from Data on the Mature T Cell Repertoire, Immunol. 164, 121-128.
  55. Detours, V., Mehr, R., & Perelson, A. S., (1999) A Quantitative Theory of Affinity-Driven T Cell Repertoire Selection, theor. Biol. 200, 389-403.
  56. Detours, V., & Perelson, A. S., (1999), Explaining High Alloreactivity as a Quantitative Consequence of Affinity-Driven T Cell Selection, Nat. Acad. Sci. USA 96, 5153-5158.
  57. Detours, V., Sulzer, B., & Perelson A. S., (1996), Size and Connectivity of the Idiotypic Network are Independent of the Discreteness of the Affinity Distribution, theor. Biol. 183, 408-416.
  58. Bersini, H., & Detours, V. #, (1994), Asynchrony Induces Stability in Cellular Automata Based Models, in Proceedings of the Fourth Conference on Artificial Life, Brooks, R. A., Maes, P., Eds. MIT Press.
  59. Detours,V. #, Bersini, H., Stewart, J., Varela, F. J., (1994), Development of Idiotypic Network in Shape Space, theor. Biol. 170, 401-414.