Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

Abstract

Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited by the cost and quality of annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels and operating via the automatic discovery of discriminatory features in image tiles. Tiles are grouped into morphologically similar clusters which constitute an atlas of histomorphological phenotypes (HP-Atlas), revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. These properties are maintained in a multi-cancer study.

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Quiros, Adalberto Claudio
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Coudray, Nicolas
Author

Coudray, Nicolas and Juarez, Michelle C. and Criscito, Maressa C. and Claudio Quiros, Adalberto and Wilken, Reason and Jackson Cullison, Stephanie R. and Stevenson, Mary L. and Doudican, Nicole A. and Yuan, Ke and Aquino, Jamie D. and Klufas, Daniel M. and North, Jeffrey P. and Yu, Siegrid S. and Murad, Fadi and Ruiz, Emily and Schmults, Chrysalyne D. and Cardona Machado, Cristian D. and Cañueto, Javier and Choudhary, Anirudh and Hughes, Alysia N. and Stockard, Alyssa and Leibovit-Reiben, Zachary and Mangold, Aaron R. and Tsirigos, Aristotelis and Carucci, John A. (2025) Self supervised artificial intelligence predicts poor outcome from primary cutaneous squamous cell carcinoma at diagnosis. npj Digital Medicine, 8 (1): 105. ISSN 2398-6352

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Yeaton, Anna
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Yang, Xinyu
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Liu, Bojing
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Le, Hortense
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Chiriboga, Luis
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Karimkhan, Afreen
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Narula, Navneet
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Moore, David A.
Author

Frankell, Alexander M. and Dietzen, Michelle and Al Bakir, Maise and Lim, Emilia L. and Karasaki, Takahiro and Ward, Sophia and Veeriah, Selvaraju and Colliver, Emma and Huebner, Ariana and Bunkum, Abigail and Hill, Mark S. and Grigoriadis, Kristiana and Moore, David A. and Black, James R. M. and Liu, Wing Kin and Thol, Kerstin and Pich, Oriol and Watkins, Thomas B. K. and Naceur-Lombardelli, Cristina and Cook, Daniel E. and Salgado, Roberto and Wilson, Gareth A. and Bailey, Chris and Angelova, Mihaela and Bentham, Robert and Martínez-Ruiz, Carlos and Abbosh, Christopher and Nicholson, Andrew G. and Le Quesne, John and Biswas, Dhruva and Rosenthal, Rachel and Puttick, Clare and Hessey, Sonya and Lee, Claudia and Prymas, Paulina and Toncheva, Antonia and Smith, Jon and Xing, Wei and Nicod, Jerome and Price, Gillian and Kerr, Keith M. and Naidu, Babu and Middleton, Gary and Blyth, Kevin G. and Fennell, Dean A. and Forster, Martin D. and Lee, Siow Ming and Falzon, Mary and Hewish, Madeleine and Shackcloth, Michael J. and Lim, Eric and Benafif, Sarah and Russell, Peter and Boleti, Ekaterini and Krebs, Matthew G. and Lester, Jason F. and Papadatos-Pastos, Dionysis and Ahmad, Tanya and Thakrar, Ricky M. and Lawrence, David and Navani, Neal and Janes, Sam M. and Dive, Caroline and Blackhall, Fiona H. and Summers, Yvonne and Cave, Judith and Marafioti, Teresa and Herrero, Javier and Quezada, Sergio A. and Peggs, Karl S. and Schwarz, Roland F. and Van Loo, Peter and Miedema, Daniël M. and Birkbak, Nicolai J. and Hiley, Crispin T. and Hackshaw, Allan and Zaccaria, Simone and TRACERx Consortium and Jamal-Hanjani, Mariam and McGranahan, Nicholas and Swanton, Charles (2024) Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature, 631 (8022): E15. ISSN 1476-4687

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Park, Christopher Y.
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Pass, Harvey
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Moreira, Andre L.
Author

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Le Quesne, John
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Frankell, Alexander M. and Dietzen, Michelle and Al Bakir, Maise and Lim, Emilia L. and Karasaki, Takahiro and Ward, Sophia and Veeriah, Selvaraju and Colliver, Emma and Huebner, Ariana and Bunkum, Abigail and Hill, Mark S. and Grigoriadis, Kristiana and Moore, David A. and Black, James R. M. and Liu, Wing Kin and Thol, Kerstin and Pich, Oriol and Watkins, Thomas B. K. and Naceur-Lombardelli, Cristina and Cook, Daniel E. and Salgado, Roberto and Wilson, Gareth A. and Bailey, Chris and Angelova, Mihaela and Bentham, Robert and Martínez-Ruiz, Carlos and Abbosh, Christopher and Nicholson, Andrew G. and Le Quesne, John and Biswas, Dhruva and Rosenthal, Rachel and Puttick, Clare and Hessey, Sonya and Lee, Claudia and Prymas, Paulina and Toncheva, Antonia and Smith, Jon and Xing, Wei and Nicod, Jerome and Price, Gillian and Kerr, Keith M. and Naidu, Babu and Middleton, Gary and Blyth, Kevin G. and Fennell, Dean A. and Forster, Martin D. and Lee, Siow Ming and Falzon, Mary and Hewish, Madeleine and Shackcloth, Michael J. and Lim, Eric and Benafif, Sarah and Russell, Peter and Boleti, Ekaterini and Krebs, Matthew G. and Lester, Jason F. and Papadatos-Pastos, Dionysis and Ahmad, Tanya and Thakrar, Ricky M. and Lawrence, David and Navani, Neal and Janes, Sam M. and Dive, Caroline and Blackhall, Fiona H. and Summers, Yvonne and Cave, Judith and Marafioti, Teresa and Herrero, Javier and Quezada, Sergio A. and Peggs, Karl S. and Schwarz, Roland F. and Van Loo, Peter and Miedema, Daniël M. and Birkbak, Nicolai J. and Hiley, Crispin T. and Hackshaw, Allan and Zaccaria, Simone and TRACERx Consortium and Jamal-Hanjani, Mariam and McGranahan, Nicholas and Swanton, Charles (2024) Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature, 631 (8022): E15. ISSN 1476-4687

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Tsirigos, Aristotelis
Author

Coudray, Nicolas and Juarez, Michelle C. and Criscito, Maressa C. and Claudio Quiros, Adalberto and Wilken, Reason and Jackson Cullison, Stephanie R. and Stevenson, Mary L. and Doudican, Nicole A. and Yuan, Ke and Aquino, Jamie D. and Klufas, Daniel M. and North, Jeffrey P. and Yu, Siegrid S. and Murad, Fadi and Ruiz, Emily and Schmults, Chrysalyne D. and Cardona Machado, Cristian D. and Cañueto, Javier and Choudhary, Anirudh and Hughes, Alysia N. and Stockard, Alyssa and Leibovit-Reiben, Zachary and Mangold, Aaron R. and Tsirigos, Aristotelis and Carucci, John A. (2025) Self supervised artificial intelligence predicts poor outcome from primary cutaneous squamous cell carcinoma at diagnosis. npj Digital Medicine, 8 (1): 105. ISSN 2398-6352

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Yuan, Ke
Author

Farndale, Lucas and Insall, Robert and Yuan, Ke (2025) TriDeNT: Triple deep network training for privileged knowledge distillation in histopathology. Medical Image Analysis, 102: 103479. ISSN 1361-8415

Ji, Yanni and Cutiongco, Marie F.A. and Jensen, Bjørn Sand and Yuan, Ke (2025) Generating realistic single-cell images from CellProfiler representations. Medical Image Analysis. ISSN 1361-8415 (In Press)

Coudray, Nicolas and Juarez, Michelle C. and Criscito, Maressa C. and Claudio Quiros, Adalberto and Wilken, Reason and Jackson Cullison, Stephanie R. and Stevenson, Mary L. and Doudican, Nicole A. and Yuan, Ke and Aquino, Jamie D. and Klufas, Daniel M. and North, Jeffrey P. and Yu, Siegrid S. and Murad, Fadi and Ruiz, Emily and Schmults, Chrysalyne D. and Cardona Machado, Cristian D. and Cañueto, Javier and Choudhary, Anirudh and Hughes, Alysia N. and Stockard, Alyssa and Leibovit-Reiben, Zachary and Mangold, Aaron R. and Tsirigos, Aristotelis and Carucci, John A. (2025) Self supervised artificial intelligence predicts poor outcome from primary cutaneous squamous cell carcinoma at diagnosis. npj Digital Medicine, 8 (1): 105. ISSN 2398-6352

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