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1. Transcriptional signals of transformation in human cancer

Author

Kildisiute, Gerda, Kalyva, Maria, Elmentaite, Rasa, van Dongen, Stijn, Thevanesan, Christine, Piapi, Alice, Ambridge, Kirsty, Prigmore, Elena, Haniffa, Muzlifah, Teichmann, Sarah A., Straathof, Karin, Cortés-Ciriano, Isidro, Behjati, Sam, and Young, Matthew D.

Published
2024
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2. Targetable NOTCH1 rearrangements in reninoma

Author

Treger, Taryn D., Lawrence, John E. G., Anderson, Nathaniel D., Coorens, Tim H. H., Letunovska, Aleksandra, Abby, Emilie, Lee-Six, Henry, Oliver, Thomas R. W., Al-Saadi, Reem, Tullus, Kjell, Morcrette, Guillaume, Hutchinson, J. Ciaran, Rampling, Dyanne, Sebire, Neil, Pritchard-Jones, Kathy, Young, Matthew D., Mitchell, Thomas J., Jones, Philip H., Tran, Maxine, Behjati, Sam, and Chowdhury, Tanzina

Published
2023
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5. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer

Author

Li, Ruoyan, Ferdinand, John R., Loudon, Kevin W., Bowyer, Georgina S., Laidlaw, Sean, Muyas, Francesc, Mamanova, Lira, Neves, Joana B., Bolt, Liam, Fasouli, Eirini S., Lawson, Andrew R.J., Young, Matthew D., Hooks, Yvette, Oliver, Thomas R.W., Butler, Timothy M., Armitage, James N., Aho, Tev, Riddick, Antony C.P., Gnanapragasam, Vincent, Welsh, Sarah J., Meyer, Kerstin B., Warren, Anne Y., Tran, Maxine G.B., Stewart, Grant D., Cortés-Ciriano, Isidro, Behjati, Sam, Clatworthy, Menna R., Campbell, Peter J., Teichmann, Sarah A., and Mitchell, Thomas J.

Published
2022
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6. Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Author

Khabirova, Eleonora, Jardine, Laura, Coorens, Tim H. H., Webb, Simone, Treger, Taryn D., Engelbert, Justin, Porter, Tarryn, Prigmore, Elena, Collord, Grace, Piapi, Alice, Teichmann, Sarah A., Inglott, Sarah, Williams, Owen, Heidenreich, Olaf, Young, Matthew D., Straathof, Karin, Bomken, Simon, Bartram, Jack, Haniffa, Muzlifah, and Behjati, Sam

Published
2022
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7. Clonal diversification and histogenesis of malignant germ cell tumours

Author

Oliver, Thomas R. W., Chappell, Lia, Sanghvi, Rashesh, Deighton, Lauren, Ansari-Pour, Naser, Dentro, Stefan C., Young, Matthew D., Coorens, Tim H. H., Jung, Hyunchul, Butler, Tim, Neville, Matthew D. C., Leongamornlert, Daniel, Sanders, Mathijs A., Hooks, Yvette, Cagan, Alex, Mitchell, Thomas J., Cortes-Ciriano, Isidro, Warren, Anne Y., Wedge, David C., Heer, Rakesh, Coleman, Nicholas, Murray, Matthew J., Campbell, Peter J., Rahbari, Raheleh, and Behjati, Sam

Published
2022
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9. The driver landscape of sporadic chordoma.

Author

Tarpey, Patrick S, Behjati, Sam, Young, Matthew D, Martincorena, Inigo, Alexandrov, Ludmil B, Farndon, Sarah J, Guzzo, Charlotte, Hardy, Claire, Latimer, Calli, Butler, Adam P, Teague, Jon W, Shlien, Adam, Futreal, P Andrew, Shah, Sohrab, Bashashati, Ali, Jamshidi, Farzad, Nielsen, Torsten O, Huntsman, David, Baumhoer, Daniel, Brandner, Sebastian, Wunder, Jay, Dickson, Brendan, Cogswell, Patricia, Sommer, Josh, Phillips, Joanna J, Amary, M Fernanda, Tirabosco, Roberto, Pillay, Nischalan, Yip, Stephen, Stratton, Michael R, Flanagan, Adrienne M, and Campbell, Peter J

Subjects
Cell Line, Tumor, Humans, Chordoma, Bone Neoplasms, T-Box Domain Proteins, Fetal Proteins, Vesicular Transport Proteins, Case-Control Studies, Gene Duplication, Mutation, Polymorphism, Single Nucleotide, Phosphatidylinositol 3-Kinases, Class I Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Polymorphism, Single Nucleotide
Abstract

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

Published
2017

10. Quantification of stochastic fragmentation of self-gravitating discs

Author

Young, Matthew D. and Clarke, Cathie J.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics
Abstract

Using 2D smoothed particle hydrodynamics, we investigate the distribution of wait times between strong shocks in a turbulent, self-gravitating accretion disc. We show the resulting distributions do not depend strongly on the cooling time or resolution of the disc and that they are consistent with the predictions of earlier work (Young & Clarke 2015; Cossins et al. 2009, 2010). We use the distribution of wait times between shocks to estimate the likelihood of stochastic fragmentation by gradual contraction of shear-resistant clumps on the cooling time scale. We conclude that the stochastic fragmentation mechanism (Paardekooper 2012) cannot change the radius at which fragmentation is possible by more than ~20%, restricting direct gravitational collapse as a mechanism for giant planet formation to the outer regions of protoplanetary discs., Comment: Accepted for publication in MNRAS. 6 pages and 3 figures

Published
2015
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11. Binary accretion rates: dependence on temperature and mass-ratio

Author

Young, Matthew D. and Clarke, Cathie J.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies, Astrophysics - High Energy Astrophysical Phenomena
Abstract

We perform a series of 2D smoothed particle hydrodynamics (SPH) simulations of gas accretion onto binaries via a circumbinary disc, for a range of gas temperatures and binary mass ratios ($q$). We show that increasing the gas temperature increases the accretion rate onto the primary for all values of the binary mass ratio: for example, for $q=0.1$ and a fixed binary separation, an increase of normalised sound speed by a factor of $5$ (from our "cold" to "hot" simulations) changes the fraction of the accreted gas that flows on to the primary from $ 10\%$ to $\sim40\%$. We present a simple parametrisation for the average accretion rate of each binary component accurate to within a few percent and argue that this parametrisation (rather than those in the literature based on warmer simulations) is relevant to supermassive black hole accretion and all but the widest stellar binaries. We present trajectories for the growth of $q$ during circumbinary disc accretion and argue that the period distribution of stellar "twin" binaries is strong evidence for the importance of circumbinary accretion. We also show that our parametrisation of binary accretion increases the minimum mass ratio needed for spin alignment of supermassive black holes to $q \sim 0.4$, with potentially important implications for the magnitude of velocity kicks acquired during black hole mergers., Comment: Accepted for publication in MNRAS. 8 pages, 7 figures and 1 table

Published
2015
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12. Dependence of fragmentation in self-gravitating accretion discs on small scale structure

Author

Young, Matthew D. and Clarke, Cathie J.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

We propose a framework for understanding the fragmentation criterion for self-gravitating discs which, in contrast to studies that emphasise the `gravoturbulent' nature of such discs, instead focuses on the properties of their quasi-regular spiral structures. Within this framework there are two evolutionary paths to fragmentation: i) collapse on the free-fall time, which requires that the ratio of cooling time to dynamical time ($\beta$) $< 3$ and ii) quasistatic collapse on the cooling time at a rate that is sufficiently fast that fragments are compact enough to withstand disruption when they encounter spiral features in the disc. We perform 2D grid simulations which demonstrate numerically converged fragmentation at $\beta < 3$ (in good agreement with Paardekooper et al. (2011) and others) and argue that this is a consequence of the fact that such simulations smooth the gravitational force on the scale $H$, the scale height of the disc. Such simulations thus only allow fragmentation via route i) above since they suppress the quasistatic contraction of fragments on scales $< H$; the inability of fragments to contract to significantly smaller scales then renders them susceptible to disruption at the next spiral arm encounter. On the other hand, 3D simulations indeed show fragmentation at higher $\beta$ via route ii). We derive an analytic prediction of fragmentation by route ii) when $\beta \lesssim 12$, based on the requirement that fragments must contract sufficiently to withstand disruption by spiral arms. We also discuss the necessary numerical requirements on both grid based and SPH codes if they are to model fragmentation via route ii)., Comment: Accepted for publication in MNRAS. 8 pages and 2 figures

Published
2015

13. The evolution of the mass ratio of accreting binaries: the role of gas temperature

Author

Young, Matthew D., Baird, Jonathon T., and Clarke, Cathie J.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

We explore an unresolved controversy in the literature about the accuracy of Smoothed Particle Hydrodynamics (SPH) in modeling the accretion of gas onto a binary system, a problem with important applications to the evolution of proto-binaries as well as accreting binary super massive black holes. It has previously been suggested that SPH fails to model the flow of loosely bound material from the secondary to primary Roche lobe and that its general prediction that accretion drives mass ratios upwards is numerically flawed. Here we show with 2D SPH that this flow from secondary to primary Roche lobe is a sensitive function of gas temperature and that this largely explains the conflicting claims in the literature which have hitherto been based on either 'cold' SPH simulations or 'hot' grid based calculations. We present simulations of a specimen 'cold' and 'hot' accretion scenario which are numerically converged and evolved into a steady state. Our analysis of the conservation of the Jacobi integral of accreting particles indicates that our results are not strongly compromised by numerical dissipation. We also explore the low resolution limit and find that simulations where the ratio of SPH smoothing length to disc scale height at the edge of the circumsecondary is less than 1 accurately capture binary accretion rates., Comment: Accepted for publication in MNRAS. 9 pages, 7 figures and 2 tables

Published
2014
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15. Single cell transcriptomics reveals chondrocyte differentiation dynamics in vivo and in vitro

Author

Lawrence, John E G, primary, Woods, Steven, additional, Roberts, Kenny, additional, Sumanaweera, Dinithi N, additional, Balogh, Petra, additional, Predeus, Alexander V, additional, He, Peng, additional, Li, Tong, additional, Polanski, Krzysztof, additional, Prigmore, Elena, additional, Tuck, Elizabeth, additional, Mamanova, Lira, additional, Zhou, Di, additional, Webb, Simone, additional, Jardine, Laura, additional, He, Xiaoling, additional, Barker, Roger A, additional, Haniffa, Muzlifah, additional, Flanagan, Adrienne M, additional, Young, Matthew D, additional, Behjati, Sam, additional, Bayraktar, Omer, additional, Kimber, Susan J, additional, and Teichmann, Sarah, additional

Published
2023
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16. Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours

Author

Custers, Lars, Khabirova, Eleonora, Coorens, Tim H. H., Oliver, Thomas R. W., Calandrini, Camilla, Young, Matthew D., Vieira Braga, Felipe A., Ellis, Peter, Mamanova, Lira, Segers, Heidi, Maat, Arie, Kool, Marcel, Hoving, Eelco W., van den Heuvel-Eibrink, Marry M., Nicholson, James, Straathof, Karin, Hook, Liz, de Krijger, Ronald R., Trayers, Claire, Allinson, Kieren, Behjati, Sam, and Drost, Jarno

Published
2021
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17. Single cell derived mRNA signals across human kidney tumors

Author

Young, Matthew D., Mitchell, Thomas J., Custers, Lars, Margaritis, Thanasis, Morales-Rodriguez, Francisco, Kwakwa, Kwasi, Khabirova, Eleonora, Kildisiute, Gerda, Oliver, Thomas R. W., de Krijger, Ronald R., van den Heuvel-Eibrink, Marry M., Comitani, Federico, Piapi, Alice, Bugallo-Blanco, Eva, Thevanesan, Christine, Burke, Christina, Prigmore, Elena, Ambridge, Kirsty, Roberts, Kenny, Braga, Felipe A. Vieira, Coorens, Tim H. H., Del Valle, Ignacio, Wilbrey-Clark, Anna, Mamanova, Lira, Stewart, Grant D., Gnanapragasam, Vincent J., Rampling, Dyanne, Sebire, Neil, Coleman, Nicholas, Hook, Liz, Warren, Anne, Haniffa, Muzlifah, Kool, Marcel, Pfister, Stefan M., Achermann, John C., He, Xiaoling, Barker, Roger A., Shlien, Adam, Bayraktar, Omer A., Teichmann, Sarah A., Holstege, Frank C., Meyer, Kerstin B., Drost, Jarno, Straathof, Karin, and Behjati, Sam

Published
2021
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18. The interplay of long non-coding RNAs and MYC in cancer

Author

Hamilton, Michael J, Young, Matthew D, Sauer, Silvia, and Martinez, Ernest

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Human Genome, Cancer, Genetics, Biotechnology, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance, lncRNA, MYC, epigenetics, chromatin, transcription, cancer, Zoology, Medical physiology
Abstract

Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are changing how researchers view eukaryotic gene regulation. Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. Investigations exploring the dynamic interactions between lncRNAs and MYC, referred to as the lncRNA-MYC network, have proven to be especially complex. Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer.

Published
2015

19. Reliable estimation of the column density in Smoothed Particle Hydrodynamic simulations

Author

Young, Matthew D., Bertram, Erik, Moeckel, Nick, and Clarke, Cathie J.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

We describe a simple method for estimating the vertical column density in Smoothed Particle Hydrodynamics (SPH) simulations of discs. As in the method of Stamatellos et al. (2007), the column density is estimated using pre-computed local quantities and is then used to estimate the radiative cooling rate. The cooling rate is a quantity of considerable importance, for example, in assessing the probability of disc fragmentation. Our method has three steps: (i) the column density from the particle to the mid plane is estimated using the vertical component of the gravitational acceleration, (ii) the "total surface density" from the mid plane to the surface of the disc is calculated, (iii) the column density from each particle to the surface is calculated from the difference between (i) and (ii). This method is shown to greatly improve the accuracy of column density estimates in disc geometry compared with the method of Stamatellos. On the other hand, although the accuracy of our method is still acceptable in the case of high density fragments formed within discs, we find that the Stamatellos method performs better than our method in this regime. Thus, a hybrid method (where the method is switched in regions of large over-density) may be optimal., Comment: Accepted for publication in MNRAS. 13 pages, 21 figures and 1 table

Published
2012
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20. Pulsar magnetic alignment and the pulsewidth-age relation

Author

Young, Matthew D. T., Chan, Lee S., Burman, Ron R., and Blair, David G.

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

Using pulsewidth data for 872 isolated radio pulsars we test the hypothesis that pulsars evolve through a progressive narrowing of the emission cone combined with progressive alignment of the spin and magnetic axes. The new data provide strong evidence for the alignment over a time-scale of about 1 Myr with a log standard deviation of around 0.8 across the observed population. This time-scale is shorter than the time-scale of about 10 Myr found by previous authors, but the log standard deviation is larger. The results are inconsistent with models based on magnetic field decay alone or monotonic counter-alignment to orthogonal rotation. The best fits are obtained for a braking index parameter n_gamma approximately equal to 2.3, consistent the mean of the six measured values, but based on a much larger sample of young pulsars. The least-squares fitted models are used to predict the mean inclination angle between the spin and magnetic axes as a function of log characteristic age. Comparing these predictions to existing estimates it is found that the model in which pulsars are born with a random angle of inclination gives the best fit to the data. Plots of the mean beaming fraction as a function of characteristic age are presented using the best-fitting model parameters., Comment: 13 pages, 11 figures, Accepted for publication in MNRAS

Published
2009
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21. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors

Author

Anderson, Nathaniel D., de Borja, Richard, Young, Matthew D., Fuligni, Fabio, Rosic, Andrej, Roberts, Nicola D., Hajjar, Simon, Layeghifard, Mehdi, Novokmet, Ana, Kowalski, Paul E., Anaka, Matthew, Davidson, Scott, Zarrei, Mehdi, Said, Badr Id, Schreiner, L. Christine, Marchand, Remi, Sitter, Joseph, Gokgoz, Nalan, Brunga, Ledia, Graham, Garrett T., Fullam, Anthony, Pillay, Nischalan, Toretsky, Jeffrey A., Yoshida, Akihiko, Shibata, Tatsuhiro, Metzler, Markus, Somers, Gino R., Scherer, Stephen W., Flanagan, Adrienne M., Campbell, Peter J., Schiffman, Joshua D., Shago, Mary, Alexandrov, Ludmil B., Wunder, Jay S., Andrulis, Irene L., Malkin, David, Behjati, Sam, and Shlien, Adam

Published
2018

22. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors

Author

Young, Matthew D., Mitchell, Thomas J., Braga, Felipe A. Vieira, Tran, Maxine G. B., Stewart, Benjamin J., Ferdinand, John R., Collord, Grace, Botting, Rachel A., Popescu, Dorin-Mirel, Loudon, Kevin W., Vento-Tormo, Roser, Stephenson, Emily, Cagan, Alex, Farndon, Sarah J., Del Castillo Velasco-Herrera, Martin, Guzzo, Charlotte, Richoz, Nathan, Mamanova, Lira, Aho, Tevita, Armitage, James N., Riddick, Antony C. P., Mushtaq, Imran, Farrell, Stephen, Rampling, Dyanne, Nicholson, James, Filby, Andrew, Burge, Johanna, Lisgo, Steven, Maxwell, Patrick H., Lindsay, Susan, Warren, Anne Y., Stewart, Grant D., Sebire, Neil, Coleman, Nicholas, Haniffa, Muzlifah, Teichmann, Sarah A., Clatworthy, Menna, and Behjati, Sam

Published
2018

24. A Resonant-Mode Model of Pulsar Radio Emission

Author

Young, Matthew D. T.

Subjects
Astrophysics
Abstract

It is argued that the polar gap and flux tube in the pulsar magnetosphere act as a resonant cavity/waveguide system which is excited by oscillations in the primary beam current and accelerating potential. The modes will be converted, probably scattered, to produce radio beams in the frequency range of those observed., Comment: 4 pages, 1 figure. To appear in "Young Neutron Stars and Their Environments" (IAU Symposium 218, ASP Conference Proceedings), eds F. Camilo and B. M. Gaensler

Published
2003

25. Decoding human fetal liver haematopoiesis

Author

Popescu, Dorin-Mirel, Botting, Rachel A., Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, Calderbank, Emily F., Polanski, Krzysztof, Goh, Issac, Efremova, Mirjana, Acres, Meghan, Maunder, Daniel, Vegh, Peter, Gitton, Yorick, Park, Jong-Eun, Vento-Tormo, Roser, Miao, Zhichao, Dixon, David, Rowell, Rachel, McDonald, David, Fletcher, James, Poyner, Elizabeth, Reynolds, Gary, Mather, Michael, Moldovan, Corina, Mamanova, Lira, Greig, Frankie, Young, Matthew D., Meyer, Kerstin B., Lisgo, Steven, Bacardit, Jaume, Fuller, Andrew, Millar, Ben, Innes, Barbara, Lindsay, Susan, Stubbington, Michael J. T., Kowalczyk, Monika S., Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L., Slyper, Michal, Rozenblatt-Rosen, Orit, Filby, Andrew, Carey, Peter, Villani, Alexandra-Chloé, Roy, Anindita, Regev, Aviv, Chédotal, Alain, Roberts, Irene, Göttgens, Berthold, Behjati, Sam, Laurenti, Elisa, Teichmann, Sarah A., and Haniffa, Muzlifah

Published
2019
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27. An integrated single-cell analysis of human adrenal cortex development

Author

del Valle, Ignacio, primary, Young, Matthew D., additional, Kildisiute, Gerda, additional, Ogunbiyi, Olumide K., additional, Buonocore, Federica, additional, Simcock, Ian C., additional, Khabirova, Eleonora, additional, Crespo, Berta, additional, Moreno, Nadjeda, additional, Brooks, Tony, additional, Niola, Paola, additional, Swarbrick, Katherine, additional, Suntharalingham, Jenifer P., additional, McGlacken-Byrne, Sinead M., additional, Arthurs, Owen J., additional, Behjati, Sam, additional, and Achermann, John C., additional

Published
2023
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29. Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Author

Penkava, Frank, Velasco-Herrera, Martin Del Castillo, Young, Matthew D., Yager, Nicole, Nwosu, Lilian N., Pratt, Arthur G., Lara, Alicia Lledo, Guzzo, Charlotte, Maroof, Ash, Mamanova, Lira, Cole, Suzanne, Efremova, Mirjana, Simone, Davide, Filer, Andrew, Brown, Chrysothemis C., Croxford, Andrew L., Isaacs, John D., Teichmann, Sarah, Bowness, Paul, Behjati, Sam, and Hussein Al-Mossawi, M.

Published
2020
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30. Intra-tumour diversification in colorectal cancer at the single-cell level

Author

Roerink, Sophie F., Sasaki, Nobuo, Lee-Six, Henry, Young, Matthew D., Alexandrov, Ludmil B., Behjati, Sam, Mitchell, Thomas J., Grossmann, Sebastian, Lightfoot, Howard, Egan, David A., Pronk, Apollo, Smakman, Niels, van Gorp, Joost, Anderson, Elizabeth, Gamble, Stephen J., Alder, Chris, van de Wetering, Marc, Campbell, Peter J., Stratton, Michael R., and Clevers, Hans

Published
2018
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31. Mesenchymal Stem Cells (MSCs) Treatment Alleviates Smoke Inhalation and Burn-Induced Acute Respiratory Distress Syndrome (ARDS) by Inhibiting HMGB1-TLR4 Signal

Author

Yang, Zhangsheng, primary, Thorpe, Catherine R., additional, Cancio, Tomas S., additional, Willis, Robert P., additional, Snook, John K., additional, Necsoiu, Corina, additional, Meyer, Andrew D., additional, Cap, Andrew P., additional, Cancio, Leopoldo C., additional, Batchinsky, Andriy I., additional, Salinas, Jose, additional, and Young, Matthew D., additional

Published
2023
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32. The pathophysiology of bilateral and multifocal Wilms tumors: What we can learn from the study of predisposition syndromes

Author

Child Health, Cancer, Genetica Klinische Genetica, Welter, Nils, Brzezinski, Jack, Treece, Amy, Chintagumpala, Murali, Young, Matthew D, Perotti, Daniela, Kieran, Kathleen, Jongmans, Marjolijn C J, Murphy, Andrew J, Child Health, Cancer, Genetica Klinische Genetica, Welter, Nils, Brzezinski, Jack, Treece, Amy, Chintagumpala, Murali, Young, Matthew D, Perotti, Daniela, Kieran, Kathleen, Jongmans, Marjolijn C J, and Murphy, Andrew J

Published
2023

33. A cell atlas of human adrenal cortex development and disease

Author

del Valle, Ignacio, primary, Young, Matthew D, additional, Kildisiute, Gerda, additional, Ogunbiyi, Olumide K, additional, Buonocore, Federica, additional, Simcock, Ian C, additional, Khabirova, Eleonora, additional, Crespo, Berta, additional, Moreno, Nadjeda, additional, Brooks, Tony, additional, Niola, Paola, additional, Swarbrick, Katherine, additional, Suntharalingham, Jenifer P, additional, McGlacken-Byrne, Sinead M, additional, Arthurs, Owen J, additional, Behjati, Sam, additional, and Achermann, John C, additional

Published
2022
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35. Transcriptional signals of dedifferentiation in human cancer

Author

Kildisiute, Gerda, primary, Kalyva, Maria, additional, Elmentaite, Rasa, additional, van Dongen, Stijn, additional, Thevanesan, Christine, additional, Piapi, Alice, additional, Ambridge, Kirsty, additional, Prigmore, Elena, additional, Haniffa, Muzlifah, additional, Teichmann, Sarah A., additional, Straathof, Karin, additional, Cortés-Ciriano, Isidro, additional, Behjati, Sam, additional, and Young, Matthew D., additional

Published
2022
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38. An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Author

Collord, Grace, Tarpey, Patrick, Kurbatova, Natalja, Martincorena, Inigo, Moran, Sebastian, Castro, Manuel, Nagy, Tibor, Bignell, Graham, Maura, Francesco, Young, Matthew D., Berna, Jorge, Tubio, Jose M. C., McMurran, Chris E., Young, Adam M. H., Sanders, Mathijs, Noorani, Imran, Price, Stephen J., Watts, Colin, Leipnitz, Elke, Kirsch, Matthias, Schackert, Gabriele, Pearson, Danita, Devadass, Abel, Ram, Zvi, Collins, V. Peter, Allinson, Kieren, Jenkinson, Michael D., Zakaria, Rasheed, Syed, Khaja, Hanemann, C. Oliver, Dunn, Jemma, McDermott, Michael W., Kirollos, Ramez W., Vassiliou, George S., Esteller, Manel, Behjati, Sam, Brazma, Alvis, Santarius, Thomas, and McDermott, Ultan

Published
2018
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39. ATRT-10. Single-cell transcriptional profiling of ATRTs reveals heterogeneous signatures of tumor and non-malignant cell populations

Author

Blanco-Carmona, Enrique, primary, Büllesbach, Annette, additional, Federico, Aniello, additional, Liu, Ilon, additional, Young, Matthew D, additional, Kildisuite, Gerda, additional, Behjati, Sam, additional, Vibhakar, Rajeev, additional, Donson, Andrew, additional, Foreman, Nicholas, additional, Hovestadt, Volker, additional, Shaw, McKenzie, additional, Chi, Susan, additional, Frühwald, Michael, additional, Drost, Jarno, additional, Korshunov, Andrey, additional, Hasselblatt, Martin, additional, Pfister, Stefan M, additional, Jäger, Natalie, additional, Johann, Pascal, additional, Filbin, Mariella, additional, and Kool, Marcel, additional

Published
2022
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40. Clonal diversification and histogenesis of malignant germ cell tumours

Author

Oliver, Thomas R.W., Chappell, Lia, Sanghvi, Rashesh, Deighton, Lauren, Ansari-Pour, Naser, Dentro, Stefan C., Young, Matthew D., Coorens, Tim H.H., Jung, Hyunchul, Butler, Tim, Neville, Matthew D.C., Leongamornlert, Daniel, Sanders, Mathijs A., Hooks, Yvette, Cagan, Alex, Mitchell, Thomas J., Cortes-Ciriano, Isidro, Warren, Anne Y., Wedge, David C., Heer, Rakesh, Coleman, Nicholas, Murray, Matthew J., Campbell, Peter J., Rahbari, Raheleh, Behjati, Sam, Oliver, Thomas R.W., Chappell, Lia, Sanghvi, Rashesh, Deighton, Lauren, Ansari-Pour, Naser, Dentro, Stefan C., Young, Matthew D., Coorens, Tim H.H., Jung, Hyunchul, Butler, Tim, Neville, Matthew D.C., Leongamornlert, Daniel, Sanders, Mathijs A., Hooks, Yvette, Cagan, Alex, Mitchell, Thomas J., Cortes-Ciriano, Isidro, Warren, Anne Y., Wedge, David C., Heer, Rakesh, Coleman, Nicholas, Murray, Matthew J., Campbell, Peter J., Rahbari, Raheleh, and Behjati, Sam

Abstract

Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we study the relationship of histogenesis and clonal diversification in GCTs by analysing the genomes and transcriptomes of 547 microdissected histological units. We find no correlation between genomic and histological heterogeneity. However, we identify unifying features including the retention of fetal developmental transcripts across tissues, expression changes on chromosome 12p, and a conserved somatic evolutionary sequence of whole genome duplication followed by clonal diversification. While this pattern is preserved across all GCTs, the developmental timing of the duplication varies between prepubertal and postpubertal cases. In addition, tumours of younger children exhibit distinct substitution signatures which may lend themselves as potential biomarkers for risk stratification. Our findings portray the extensive diversification of GCT tissues and genetic subclones as randomly distributed, while identifying overarching transcriptional and genomic features.

Published
2022

42. Clonal diversification and histogenesis of malignant germ cell tumours

Author

Oliver, Thomas R. W., primary, Chappell, Lia, additional, Sanghvi, Rashesh, additional, Deighton, Lauren, additional, Ansari-Pour, Naser, additional, Dentro, Stefan C., additional, Young, Matthew D., additional, Coorens, Tim H. H., additional, Jung, Hyunchul, additional, Butler, Tim, additional, Neville, Matthew D. C., additional, Leongamornlert, Daniel, additional, Sanders, Mathijs, additional, Hooks, Yvette, additional, Cagan, Alex, additional, Mitchell, Thomas J., additional, Cortes-Ciriano, Isidro, additional, Warren, Anne Y., additional, Wedge, David C., additional, Heer, Rakesh, additional, Coleman, Nicholas, additional, Murray, Matthew J., additional, Campbell, Peter J., additional, Rahbari, Raheleh, additional, and Behjati, Sam, additional

Published
2022
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43. Single cell mRNA signals reveal a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Author

Khabirova, Eleonora, primary, Jardine, Laura, additional, Coorens, Tim H. H., additional, Webb, Simone, additional, Treger, Taryn D., additional, Englebert, Justin, additional, Porter, Tarryn, additional, Prigmore, Elena, additional, Collord, Grace, additional, Piapi, Alice, additional, Teichmann, Sarah, additional, Inglott, Sarah, additional, Williams, Owen, additional, Heidenreich, Olaf, additional, Young, Matthew D., additional, Straathof, Karin, additional, Bomken, Simon, additional, Bartram, Jack, additional, Haniffa, Muzlifah, additional, and Behjati, Sam, additional

Published
2021
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45. Multi-regional characterisation of renal cell carcinoma and microenvironment at single cell resolution

Author

Li, Ruoyan, primary, Ferdinand, John R., additional, Loudon, Kevin W., additional, Bowyer, Georgina S., additional, Mamanova, Lira, additional, Neves, Joana B., additional, Bolt, Liam, additional, Fasouli, Eirini S., additional, Lawson, Andrew R. J., additional, Young, Matthew D., additional, Hooks, Yvette, additional, Oliver, Thomas R. W., additional, Butler, Timothy M., additional, Armitage, James N., additional, Aho, Tev, additional, Riddick, Antony C. P., additional, Gnanapragasam, Vincent, additional, Welsh, Sarah J., additional, Meyer, Kerstin B., additional, Warren, Anne Y., additional, Tran, Maxine G. B., additional, Stewart, Grant D., additional, Behjati, Sam, additional, Clatworthy, Menna R., additional, Campbell, Peter J., additional, Teichmann, Sarah A., additional, and Mitchell, Thomas J., additional

Published
2021
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46. Inherent mosaicism and extensive mutation of human placentas

Author

Coorens, Tim H H, primary, Oliver, Thomas R W, additional, Sanghvi, Rashesh, additional, Sovio, Ulla, additional, Cook, Emma, additional, Vento-Tormo, Roser, additional, Haniffa, Muzlifah, additional, Young, Matthew D, additional, Rahbari, Raheleh, additional, Sebire, Neil, additional, Campbell, Peter J, additional, Charnock-Jones, D Stephen, additional, Smith, Gordon CS, additional, and Behjati, Sam, additional

Published
2021
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47. Inherent Mosaicism and Extensive Mutation of Human Placentas

Author

Coorens, Tim H. H., primary, Oliver, Thomas R. W., additional, Sanghvi, Rashesh, additional, Sovio, Ulla, additional, Cook, Emma, additional, Vento-Tormo, Roser, additional, Haniffa, Muzlifah, additional, Young, Matthew D., additional, Rahbari, Raheleh, additional, Sebire, Neil, additional, Campbell, Peter J., additional, Charnock-Jones, D. Stephen, additional, Smith, Gordon C. S., additional, and Behjati, Sam, additional

Published
2021
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48. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Author

Afd Pharmaceutics, Pharmaceutics, Kildisiute, Gerda, Kholosy, Waleed M, Young, Matthew D, Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R, Pacyna, Clarissa N, Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M, Langenberg-Ververgaert, Karin P S, Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C P, Tas, Michelle L, Wijnen, Marc H W A, van Noesel, Max M, Del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C, Haniffa, Muzlifah, Teichmann, Sarah A, Rampling, Dyanne, Sebire, Neil J, He, Xiaoling, de Krijger, Ronald R, Barker, Roger A, Meyer, Kerstin B, Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J, Behjati, Sam, Afd Pharmaceutics, Pharmaceutics, Kildisiute, Gerda, Kholosy, Waleed M, Young, Matthew D, Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R, Pacyna, Clarissa N, Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M, Langenberg-Ververgaert, Karin P S, Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C P, Tas, Michelle L, Wijnen, Marc H W A, van Noesel, Max M, Del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C, Haniffa, Muzlifah, Teichmann, Sarah A, Rampling, Dyanne, Sebire, Neil J, He, Xiaoling, de Krijger, Ronald R, Barker, Roger A, Meyer, Kerstin B, Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J, and Behjati, Sam

Published
2021

49. Single cell derived mRNA signals across human kidney tumors

Author

Groep Holstege, Pathologie Pathologen staf, Speerpunt, Zorg en O&O, Child Health, CMM Groep Burgering, Cancer, Young, Matthew D., Mitchell, Thomas J., Custers, Lars, Margaritis, Thanasis, Morales-Rodriguez, Francisco, Kwakwa, Kwasi, Khabirova, Eleonora, Kildisiute, Gerda, Oliver, Thomas R.W., de Krijger, Ronald R., van den Heuvel-Eibrink, Marry M., Comitani, Federico, Piapi, Alice, Bugallo-Blanco, Eva, Thevanesan, Christine, Burke, Christina, Prigmore, Elena, Ambridge, Kirsty, Roberts, Kenny, Braga, Felipe A.Vieira, Coorens, Tim H.H., Del Valle, Ignacio, Wilbrey-Clark, Anna, Mamanova, Lira, Stewart, Grant D., Gnanapragasam, Vincent J., Rampling, Dyanne, Sebire, Neil, Coleman, Nicholas, Hook, Liz, Warren, Anne, Haniffa, Muzlifah, Kool, Marcel, Pfister, Stefan M., Achermann, John C., He, Xiaoling, Barker, Roger A., Shlien, Adam, Bayraktar, Omer A., Teichmann, Sarah A., Holstege, Frank C., Meyer, Kerstin B., Drost, Jarno, Straathof, Karin, Behjati, Sam, Groep Holstege, Pathologie Pathologen staf, Speerpunt, Zorg en O&O, Child Health, CMM Groep Burgering, Cancer, Young, Matthew D., Mitchell, Thomas J., Custers, Lars, Margaritis, Thanasis, Morales-Rodriguez, Francisco, Kwakwa, Kwasi, Khabirova, Eleonora, Kildisiute, Gerda, Oliver, Thomas R.W., de Krijger, Ronald R., van den Heuvel-Eibrink, Marry M., Comitani, Federico, Piapi, Alice, Bugallo-Blanco, Eva, Thevanesan, Christine, Burke, Christina, Prigmore, Elena, Ambridge, Kirsty, Roberts, Kenny, Braga, Felipe A.Vieira, Coorens, Tim H.H., Del Valle, Ignacio, Wilbrey-Clark, Anna, Mamanova, Lira, Stewart, Grant D., Gnanapragasam, Vincent J., Rampling, Dyanne, Sebire, Neil, Coleman, Nicholas, Hook, Liz, Warren, Anne, Haniffa, Muzlifah, Kool, Marcel, Pfister, Stefan M., Achermann, John C., He, Xiaoling, Barker, Roger A., Shlien, Adam, Bayraktar, Omer A., Teichmann, Sarah A., Holstege, Frank C., Meyer, Kerstin B., Drost, Jarno, Straathof, Karin, and Behjati, Sam

Published
2021

50. Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours

Author

PMC Medisch specialisten, Cancer, Neurochirurgen, Speerpunt, Zorg en O&O, Child Health, Pathologie Pathologen staf, Custers, Lars, Khabirova, Eleonora, Coorens, Tim H.H., Oliver, Thomas R.W., Calandrini, Camilla, Young, Matthew D., Vieira Braga, Felipe A., Ellis, Peter, Mamanova, Lira, Segers, Heidi, Maat, Arie, Kool, Marcel, Hoving, Eelco W., van den Heuvel-Eibrink, Marry M., Nicholson, James, Straathof, Karin, Hook, Liz, de Krijger, Ronald R., Trayers, Claire, Allinson, Kieren, Behjati, Sam, Drost, Jarno, PMC Medisch specialisten, Cancer, Neurochirurgen, Speerpunt, Zorg en O&O, Child Health, Pathologie Pathologen staf, Custers, Lars, Khabirova, Eleonora, Coorens, Tim H.H., Oliver, Thomas R.W., Calandrini, Camilla, Young, Matthew D., Vieira Braga, Felipe A., Ellis, Peter, Mamanova, Lira, Segers, Heidi, Maat, Arie, Kool, Marcel, Hoving, Eelco W., van den Heuvel-Eibrink, Marry M., Nicholson, James, Straathof, Karin, Hook, Liz, de Krijger, Ronald R., Trayers, Claire, Allinson, Kieren, Behjati, Sam, and Drost, Jarno

Published
2021

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