Voet Group | Single-cell genomics

Voet Group | Single-cell genomics

Voet Group

Our Research and Approach

We develop methods to determine all classes of genetic variants in the genome of a single cell, as well as the RNA molecules the cell transcribes, to enable the exploration of the genetic differences between cells in a person's body and the relation of this diversity to disease.

The nature and pace of genome mutation in normal and diseased cells is largely unknown. Sequencing the DNA of single cells is a powerful method to study genome mutation in cells, right down to each generation of the cell. It will also enable the dissection and comparison of the genetic content of individual cells in normal organs and diseased tissues, providing insights into how fundamental processes of genome maintenance operate, how these processes may be perturbed in disease, and how somatic mutation may cause disease. Furthermore, single-cell genomics will accelerate our understanding of the genetic diversity that develops in a person's cells over time and its relation to phenotypes and disease development.

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People

Voet, Thierry
Thierry Voet, PhD
Group Leader

Thierry Voet is co-founder and member of the Sanger Institute-EBI Single-Cell Genomics Centre.


Key Projects, Collaborations, Tools & Data

Key tools: We have developed G&T-seq, a method for genome and transcriptome sequencing of the same single cell (Macaulay et al. Nature Methods. 2015 Jun;12(6):519-22). Key collaborative projects: We are partner in two Wellcome Trust Strategic Award projects “Tracing early mammalian lineage decisions by single cell genomics” and “The Homunculus in our Thymus: A Cellular Genomics Approach”.

Research Programmes and Faciltites

Partners and Funders

Internal Partners

Publications

  • Concurrent whole-genome haplotyping and copy-number profiling of single cells.

    Zamani Esteki M, Dimitriadou E, Mateiu L, Melotte C, Van der Aa N et al.

    American journal of human genetics 2015;96;6;894-912

  • Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations.

    Wilson NK, Kent DG, Buettner F, Shehata M, Macaulay IC et al.

    Cell stem cell 2015;16;6;712-24

  • G&T-seq: parallel sequencing of single-cell genomes and transcriptomes.

    Macaulay IC, Haerty W, Kumar P, Li YI, Hu TX et al.

    Nature methods 2015;12;6;519-22

  • SNES makes sense? Single-cell exome sequencing evolves.

    Voet T and Van Loo P

    Genome biology 2015;16;86

  • Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    Cooper CS, Eeles R, Wedge DC, Van Loo P, Gundem G et al.

    Nature genetics 2015;47;4;367-372

  • Spatial and temporal diversity in genomic instability processes defines lung cancer evolution.

    de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC et al.

    Science (New York, N.Y.) 2014;346;6206;251-6

  • Single cell analysis of cancer genomes.

    Van Loo P and Voet T

    Current opinion in genetics & development 2014;24;82-91

  • Single cell segmental aneuploidy detection is compromised by S phase.

    Dimitriadou E, Van der Aa N, Cheng J, Voet T and Vermeesch JR

    Molecular cytogenetics 2014;7;46

  • Single cell genomics: advances and future perspectives.

    Macaulay IC and Voet T

    PLoS genetics 2014;10;1;e1004126

  • Mosaic copy number variation in human neurons.

    McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T et al.

    Science (New York, N.Y.) 2013;342;6158;632-7

  • Single-cell paired-end genome sequencing reveals structural variation per cell cycle.

    Voet T, Kumar P, Van Loo P, Cooke SL, Marshall J et al.

    Nucleic acids research 2013;41;12;6119-38

  • Genome-wide copy number profiling of single cells in S-phase reveals DNA-replication domains.

    Van der Aa N, Cheng J, Mateiu L, Zamani Esteki M, Kumar P et al.

    Nucleic acids research 2013;41;6;e66

  • Next-generation sequencing of disseminated tumor cells.

    Møller EK, Kumar P, Voet T, Peterson A, Van Loo P et al.

    Frontiers in oncology 2013;3;320

  • Preimplantation genetic diagnosis guided by single-cell genomics.

    Van der Aa N, Zamani Esteki M, Vermeesch JR and Voet T

    Genome medicine 2013;5;8;71

  • Alzheimer's disease: A protective mutation.

    De Strooper B and Voet T

    Nature 2012;488;7409;38-9

  • Microarray analysis of copy number variation in single cells.

    Konings P, Vanneste E, Jackmaert S, Ampe M, Verbeke G et al.

    Nature protocols 2012;7;2;281-310

  • Single-cell copy number variation detection.

    Cheng J, Vanneste E, Konings P, Voet T, Vermeesch JR and Moreau Y

    Genome biology 2011;12;8;R80

  • Breakage-fusion-bridge cycles leading to inv dup del occur in human cleavage stage embryos.

    Voet T, Vanneste E, Van der Aa N, Melotte C, Jackmaert S et al.

    Human mutation 2011;32;7;783-93

  • The human cleavage stage embryo is a cradle of chromosomal rearrangements.

    Voet T, Vanneste E and Vermeesch JR

    Cytogenetic and genome research 2011;133;2-4;160-8

  • Chromosome instability is common in human cleavage-stage embryos.

    Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P et al.

    Nature medicine 2009;15;5;577-83

  • Single-Cell (Multi)omics Technologies.

    Chappell L, Russell AJC and Voet T

    Annual review of genomics and human genetics 2018;19;15-41

  • Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures.

    Sozen B, Amadei G, Cox A, Wang R, Na E et al.

    Nature cell biology 2018

  • Early lineage segregation of multipotent embryonic mammary gland progenitors.

    Wuidart A, Sifrim A, Fioramonti M, Matsumura S, Brisebarre A et al.

    Nature cell biology 2018

  • Single-cell sequencing reveals the origin and the order of mutation acquisition in T-cell acute lymphoblastic leukemia.

    De Bie J, Demeyer S, Alberti-Servera L, Geerdens E, Segers H et al.

    Leukemia 2018

  • Identification of the tumour transition states occurring during EMT.

    Pastushenko I, Brisebarre A, Sifrim A, Fioramonti M, Revenco T et al.

    Nature 2018;556;7702;463-468

  • Pluripotent state transitions coordinate morphogenesis in mouse and human embryos.

    Shahbazi MN, Scialdone A, Skorupska N, Weberling A, Recher G et al.

    Nature 2017

  • Accurate and comprehensive analysis of single nucleotide variants and large deletions of the human mitochondrial genome in DNA and single cells.

    Zambelli F, Vancampenhout K, Daneels D, Brown D, Mertens J et al.

    European journal of human genetics : EJHG 2017;25;11;1229-1236

  • Genome stability of bovine in vivo-conceived cleavage-stage embryos is higher compared to in vitro-produced embryos.

    Tšuiko O, Catteeuw M, Zamani Esteki M, Destouni A, Bogado Pascottini O et al.

    Human reproduction (Oxford, England) 2017;32;11;2348-2357

  • Principles guiding embryo selection following genome-wide haplotyping of preimplantation embryos.

    Dimitriadou E, Melotte C, Debrock S, Esteki MZ, Dierickx K et al.

    Human reproduction (Oxford, England) 2017;32;3;687-697

  • Mutational Processes Shaping the Genome in Early Human Embryos.

    Voet T and Vermeesch JR

    Cell 2017;168;5;751-753

  • Single-Cell Multiomics: Multiple Measurements from Single Cells.

    Macaulay IC, Ponting CP and Voet T

    Trends in genetics : TIG 2017;33;2;155-168

  • Genome-wide in vivo screen identifies novel host regulators of metastatic colonization.

    van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H et al.

    Nature 2017;541;7636;233-236

  • Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing.

    Demeulemeester J, Kumar P, Møller EK, Nord S, Wedge DC et al.

    Genome biology 2016;17;1;250

  • Separation and parallel sequencing of the genomes and transcriptomes of single cells using G&T-seq.

    Macaulay IC, Teng MJ, Haerty W, Kumar P, Ponting CP and Voet T

    Nature protocols 2016;11;11;2081-103

  • Zygotes segregate entire parental genomes in distinct blastomere lineages causing cleavage-stage chimerism and mixoploidy.

    Destouni A, Zamani Esteki M, Catteeuw M, Tšuiko O, Dimitriadou E et al.

    Genome research 2016;26;5;567-78

  • Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

    Bolton H, Graham SJ, Van der Aa N, Kumar P, Theunis K et al.

    Nature communications 2016;7;11165

  • Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos.

    Goolam M, Scialdone A, Graham SJL, Macaulay IC, Jedrusik A et al.

    Cell 2016;165;1;61-74

  • Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity.

    Angermueller C, Clark SJ, Lee HJ, Macaulay IC, Teng MJ et al.

    Nature methods 2016;13;3;229-232

  • Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells.

    Macaulay IC, Svensson V, Labalette C, Ferreira L, Hamey F et al.

    Cell reports 2016;14;4;966-977

  • On the identification of low allele frequency mosaic mutations in the brains of Alzheimer's disease patients.

    Sala Frigerio C, Lau P, Troakes C, Deramecourt V, Gele P et al.

    Alzheimer's & dementia : the journal of the Alzheimer's Association 2015;11;11;1265-76

  • Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations.

    Wilson NK, Kent DG, Buettner F, Shehata M, Macaulay IC et al.

    Cell stem cell 2015;16;6;712-24

  • Concurrent whole-genome haplotyping and copy-number profiling of single cells.

    Zamani Esteki M, Dimitriadou E, Mateiu L, Melotte C, Van der Aa N et al.

    American journal of human genetics 2015;96;6;894-912

  • G&T-seq: parallel sequencing of single-cell genomes and transcriptomes.

    Macaulay IC, Haerty W, Kumar P, Li YI, Hu TX et al.

    Nature methods 2015;12;6;519-22

  • SNES makes sense? Single-cell exome sequencing evolves.

    Voet T and Van Loo P

    Genome biology 2015;16;86

  • Spatial and temporal diversity in genomic instability processes defines lung cancer evolution.

    de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC et al.

    Science (New York, N.Y.) 2014;346;6206;251-6

  • Single cell analysis of cancer genomes.

    Van Loo P and Voet T

    Current opinion in genetics & development 2014;24;82-91

  • Single cell genomics: advances and future perspectives.

    Macaulay IC and Voet T

    PLoS genetics 2014;10;1;e1004126

  • Mosaic copy number variation in human neurons.

    McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T et al.

    Science (New York, N.Y.) 2013;342;6158;632-7

  • Single-cell paired-end genome sequencing reveals structural variation per cell cycle.

    Voet T, Kumar P, Van Loo P, Cooke SL, Marshall J et al.

    Nucleic acids research 2013;41;12;6119-38

  • Meander: visually exploring the structural variome using space-filling curves.

    Pavlopoulos GA, Kumar P, Sifrim A, Sakai R, Lin ML et al.

    Nucleic acids research 2013;41;11;e118

  • Next-generation sequencing of disseminated tumor cells.

    Møller EK, Kumar P, Voet T, Peterson A, Van Loo P et al.

    Frontiers in oncology 2013;3;320

  • Preimplantation genetic diagnosis guided by single-cell genomics.

    Van der Aa N, Zamani Esteki M, Vermeesch JR and Voet T

    Genome medicine 2013;5;8;71

  • Next-generation sequencing in breast cancer: first take home messages.

    Desmedt C, Voet T, Sotiriou C and Campbell PJ

    Current opinion in oncology 2012;24;6;597-604