Computational Biology

Group Leader:
Crispin Miller

The Computational Biology group is focused on using data-driven approaches from AI and machine learning to develop a better understanding of the processes that underpin tumour growth and development. We are a highly collaborative and interdisciplinary group that integrates computer science, mathematics, bench- and clinical science. A major aspect of our work is the integration of deep-tissue phenotyping datasets captured using our Advanced Technologies – ranging from microscopy, through whole genome-, bulk- and single cell RNA sequencing, spatial transcriptomics, to multiplexed immunofluorescence and hematoxylin and eosin (H&E) stained tissue. These datasets are large enough to use AI and machine learning algorithms that seek to correlate patterns with phenotype. This is allowing us to explore aspects of tumour evolution, and to ask how the regulatory systems that control gene expression are perturbed in tumour cells. One of our goals is to use data to ‘disease position’ our preclinical models of disease against stratified patient cohorts. In this way we can ask how our discovery science datasets capture the heterogeneity of the disease and use our multimodal datasets to identify the best models to represent different patient subsets. Our group is particularly interested in the regulatory pathways that act downstream of transcription, including the processes that regulate protein translation and stability. Other projects in the group focus on uncovering novel regulatory sequences within the genome, and in making use of comparative genomics to help interpret the genome rearrangements that occur in tumour cells. Our research includes the development and finetuning of AI foundation models, and we make extensive use of our local HPC facility as well as national supercomputing resources. We have an internship scheme with STFC DiRAC to support members of the physics and astronomy community interested in bringing their skills to bear upon critical problems in cancer research. The size and complexity of our data require sophisticated approaches to manage, share and compute with them. The Data Science and Data Management Advanced Technology Team is building a FAIR-compliant data platform to support this.

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Lab Reports

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Recent Publications

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Lab Members

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Recent Publications

2026

Raffo-Iraolagoitia XL, McFarlane AJ, Laing S, Corbyn R, Arnott LWG, Fercoq F, McGarry L, Secklehner J, De Donatis M, Mackey JBG, Kruspig B, Wiesheu R, Hsieh YC, Shaw R, Rakovic K, Le Quesne J, Clark G, Nixon C, Miller C, Kirschner K, Bain CC, Murphy DJ, Coffelt SB, Carlin LM. Vγ1 γδ T cells steer airway macrophages toward a profibrotic response in an autochthonous lung cancer mouse model. Sci Adv. 2026;12(10):eadu8802.

Riggio AI, Sweeney K, Shaw R, Lawlor A, Khan A, Ferrari N, Anand J, Galbraith LC, Gilroy K, Bull C, Young AL, Athineos D, Hall H, Ghaffar F, Hughes M, Mitchell CA, Mitchell L, Nixon C, Adams PD, Roberts EW, Miller CJ, Dunne PD, Campbell KJ, Cameron ER, Blyth K. Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis. Br J Cancer. 2026.

2025

Kanellos G, Giacomelli C, Raven A, Vlahov N, Jin H, Herviou P, Malla SB, Nasreddin N, Centeno PP, Alexandrou C, Gilroy K, Baird RL, Pennel K, Munro J, Waldron JA, Hall H, Officer-Jones L, Bryson S, Strathdee D, Lilla S, Zanivan S, Morrison V, Nixon C, Ridgway RA, Miller C, Knight JRP, Campbell AD, Dunne PD, Le Quesne J, Edwards J, Park PJ, Bushell M, Sansom OJ. Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation. Nat Genet. 2025;58:100-115.

Liu D, Young F, Lamb KD, Claudio Quiros A, Pancheva A, Miller CJ, Macdonald C, Robertson DL, Yuan K. PLM-interact: extending protein language models to predict protein-protein interactions. Nat Commun. 2025;16(1):9012.

Müller M, May S, Hall H, Kendall TJ, McGarry L, Blukacz L, Nuciforo S, Georgakopoulou A, Jamieson T, Phinichkusolchit N, Dhayade S, Suzuki T, Huguet-Pradell J, Powley IR, Officer-Jones L, Pennie RL, Esteban-Fabró R, Gris-Oliver A, Pinyol R, Skalka GL, Leslie J, Hoare M, Sprangers J, Malviya G, Mackintosh A, Johnson E, McCain M, Halpin J, Kiourtis C, Nixon C, Clark G, Clark W, Shaw R, Hedley A, Drake TM, Tan EH, Neilson M, Murphy DJ, Lewis DY, Reeves HL, Le Quesne J, Mann DA, Carlin LM, Blyth K, Llovet JM, Heim MH, Sansom OJ, Miller CJ, Bird TG. Human-correlated genetic models identify precision therapy for liver cancer. Nature. 2025.

Raven A, Gilroy K, Jin H, Waldron JA, Leslie H, Munro J, Hall H, Ridgway RA, Ford CA, Gulhan DC, Vlahov N, Mills ML, Hartley A, Anderson E, Bryson S, Sphyris N, Müller M, May S, Cadden B, Nixon C, Waddell SH, Guest R, Boulter L, Barker N, Clevers H, Zhu H, Ivaska J, Strathdee D, Miller CJ, Jamieson NB, Bushell M, Park PJ, Bird TG, Sansom OJ. Hepatic zonation determines tumorigenic potential of mutant β-catenin. Nature. 2025;649:739-748.

White M, Mills ML, Millett LM, Gilroy K, Hong Y, Zeiger LB, Simpson RJ, Corry SM, Ligeza A, Lannagan TRM, Susanti S, Ridgway RA, Yazgili AS, Grzesiak L, Amirkhah R, Ford CA, Vlahov N, Tovell H, Officer-Jones L, Ficken C, Pennie R, Najumudeen AK, Raven A, Nasreddin N, Chauhan E, Papanastasiou AS, Nixon C, Morrison V, Jackstadt R, Graham JS, Miller CJ, Ross SJ, Barry ST, Pavet V, Wilson RH, Le Quesne J, Dunne PD, Tejpar S, Leedham S, Campbell AD, Sansom OJ. MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistance. Nature. 2025.

2024

Liu D, Young F, Lamb KD, Claudio Quiros A, Pancheva A, Miller C, Macdonald C, Robertson DL, Yuan K. PLM-interact: extending protein language models to predict protein-protein interactions. bioRxiv. 2024:2024.2011.2005.622169.

Malla SB, Byrne RM, Lafarge MW, Corry SM, Fisher NC, Tsantoulis PK, Mills ML, Ridgway RA, Lannagan TRM, Najumudeen AK, Gilroy KL, Amirkhah R, Maguire SL, Mulholland EJ, Belnoue-Davis HL, Grassi E, Viviani M, Rogan E, Redmond KL, Sakhnevych S, McCooey AJ, Bull C, Hoey E, Sinevici N, Hall H, Ahmaderaghi B, Domingo E, Blake A, Richman SD, Isella C, Miller C, Bertotti A, Trusolino L, Loughrey MB, Kerr EM, Tejpar S, Maughan TS, Lawler M, Campbell AD, Leedham SJ, Koelzer VH, Sansom OJ, Dunne PD. Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer. Nature Genetics. 2024.

Wiesheu R, Edwards SC, Hedley A, Hall H, Tosolini M, Fares da Silva MGF, Sumaria N, Castenmiller SM, Wardak L, Optaczy Y, Lynn A, Hill DG, Hayes AJ, Hay J, Kilbey A, Shaw R, Whyte D, Walsh PJ, Michie AM, Graham GJ, Manoharan A, Halsey C, Blyth K, Wolkers MC, Miller C, Pennington DJ, Jones GW, Fournie JJ, Bekiaris V, Coffelt SB. IL-27 maintains cytotoxic Ly6C(+) γδ T cells that arise from immature precursors. Embo j. 2024.

2023

Edwards SC, Hedley A, Hoevenaar WHM, Wiesheu R, Glauner T, Kilbey A, Shaw R, Boufea K, Batada N, Hatano S, Yoshikai Y, Blyth K, Miller C, Kirschner K, Coffelt SB. PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing γδ T cells. J Exp Med. 2023;220:e20211431.

Laing S, Kruspig B, Shaw R, Officer-Jones L, Edwards S, McKinven D, Hsieh Y-C, Powley I, Brady N, Pennie R, Kwan R, Lima A, Myrta S, Periyasamy M, Dye IC, Nixon C, Clark G, Junttila MR, Maddalo D, Miller C, Ali S, Fuchter MJ, Nickles D, Kirschner K, Brown RB, Quesne JL, Strathdee D, Coffelt SB, Roberts E, Murphy DJ. ERBB signalling contributes to immune evasion in KRAS-driven lung adenocarcinoma. bioRxiv. 2023:2023.2007.2024.550274.

Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.

Raffo-Iraolagoitia XL, McFarlane AJ, Kruspig B, Fercoq F, Secklehner J, Donatis MD, Mackey JBG, Wiesheu R, Laing S, Hsieh Y-C, Shaw R, Corbyn R, Nixon C, Miller C, Kirschner K, Bain CC, Murphy DJ, Coffelt SB, Carlin LM. γδ T cells impair airway macrophage differentiation in lung adenocarcinoma. bioRxiv. 2023:2023.2009.2014.557344.

Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.

2022

Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.

Kay EJ, Paterson K, Riero-Domingo C, Sumpton D, Däbritz JHM, Tardito S, Boldrini C, Hernandez-Fernaud JR, Athineos D, Dhayade S, Stepanova E, Gjerga E, Neilson LJ, Lilla S, Hedley A, Koulouras G, McGregor G, Jamieson C, Johson RM, Park M, Kirschner K, Miller C, Kamphorst JJ, Loayza-Puch F, Saez-Rodriguez J, Mazzone M, Blyth K, Zagoni M, Zanivan S. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism. 2022;4(6):693-710.

Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.

2021

Edwards SC, Hedley A, Hoevenaar WHM, Glauner T, Wiesheu R, Kilbey A, Shaw R, Boufea K, Batada N, Blyth K, Miller C, Kirschner K, Coffelt SB. Single-cell analysis uncovers differential regulation of lung γδ T cell subsets by the co-inhibitory molecules, PD-1 and TIM-3. bioRxiv. 2021.

Tsim S, Alexander L, Kelly C, Shaw A, Hinsley S, Clark S, Evison M, Holme J, Cameron EJ, Sharma D, Wright A, Grundy S, Grieve D, Ionescu A, Breen DP, Paramasivam E, Psallidas I, Mukherjee D, Chetty M, Cox G, Hart-Thomas A, Naseer R, Edwards J, Daneshvar C, Panchal R, Munavvar M, Ostroff R, Alexander L, Hall H, Neilson M, Miller C, McCormick C, Thomson F, Chalmers AJ, Maskell NA, Blyth KG. Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases. J Thorac Oncol. 2021;16:1705-1717.

2020

Humphrey S, Kerr A, Rattray M, Dive C, Miller CJ. A model of k-mer surprisal to quantify local sequence information content surrounding splice regions. PeerJ. 2020;8:e10063.

2019

Lallo A, Gulati S, Schenk MW, Khandelwal G, Berglund UW, Pateras IS, Chester CPE, Pham TM, Kalderen C, Frese KK, Gorgoulis VG, Miller C, Blackhall F, Helleday T, Dive C. Ex Vivo Culture of Cells Derived From Circulating Tumour Cell Xenograft to support Small Cell Lung Cancer Research and Experimental Therapeutics. Br J Pharmacol. 2019;176:436-50.

Rothwell DG, Ayub M, Cook N, Thistlethwaite F, Carter L, Dean E, Smith N, Villa S, Dransfield J, Clipson A, White D, Nessa K, Ferdous S, Howell M, Gupta A, Kilerci B, Mohan S, Frese K, Gulati S, Miller C, Jordan A, Eaton H, Hickson N, O’Brien C, Graham D, Kelly C, Aruketty S, Metcalf R, Chiramel J, Tinsley N, Vickers AJ, Kurup R, Frost H, Stevenson J, Southam S, Landers D, Wallace A, Marais R, Hughes AM, Brady G, Dive C, Krebs MG. Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nature Medicine 2019;25:738-43.

2018

Bennett L, Howell M, Memon D, Smowton C, Zhou C, Miller C. Mutation pattern analysis reveals polygenic mini-drivers associated with relapse after surgery in lung adenocarcinoma. Scientific Reports 2018;8:14830.

Hudson AM, Stephenson NL, Li C, Trotter E, Fletcher AJ, Katona G, Bieniasz-Krzywiec P, Howell M, Wirth C, Furney S, Miller CJ, Brognard J. Truncation- and motif-based pan-cancer analysis reveals tumorsuppressing kinases. Science Signaling 2018;11:526.

Kim CS, Mohan S, Ayub M, Rothwell DG, Dive C, Brady G, Miller C. In silico error correction improves cfDNA mutation calling. Bioinformatics 2018;35:2380-2385.

Lallo A, Frese KK, Morrow C, Szczepaniak Sloane R, Gulati S, Schenk MW, Trapani F, Simms N, Galvin M, Brown S, Hodgkinson CL, Priest L, Hughes AM, Lai Z, Cadogan EB, Khandelwal G, Simpson KL, Miller C, Blackhall FH, O’Connor MJ, Dive C. The combination of the PARP inhibitor olaparib and the Wee1 inhibitor AZD1775 as a new therapeutic option for small cell lung cancer. Clinical Cancer Research 2018;24:5153-64.

Torres-Ayuso P, Sahoo S, Ashton G, An E, Simms N, Galvin M, Leong HS, Frese KK, Simpson K, Cook N, Hughes A, Miller CJ, Marais R, Dive C, Krebs MG, Brognard J. Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations: a case report for a cancer of unknown primary origin. Genomic Medicine 2018;3:15.

2017

Carter L, Rothwell D, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F, Li Y, Burt DJ, Antonello J, Morrow CJ, Hodgkinson C, Morris K, Priest L, Carter M, Miller C, Hughes A, Blackhall F, Dive C, Brady G. Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Nature Medicine 2017;23:114-9.

Chiu A, Ayub M, Dive C, Brady G, Miller C. twoddpcr: an R/Bioconductor package and Shiny app for Droplet Digital PCR analysis. Bioinformatics 2017;33:2743-5.

Khandelwal G, Girotti MR, Smowton C, Taylor S, Wirth C, Dynowski M, Frese KK, Brady G, Dive C, Marais R, Miller C. Next-generation sequencing analysis and algorithms for PDX and CDX models. Molecular Cancer Research 2017;15:1012-6.

Smowton C, Balla A, Antoniades D, Miller C, Pallis G, Dikaiakos MD, Xing W. A cost-effective approach to improving performance of big genomic data analyses in clouds. Future Generation Computer Systems 2017;67:368-81.

2016

Williamson SC, Metcalf RL, Trapani F, Mohan S, Antonello J, Abbott B, Leong HS, Chester C, Simms N, Polanski R, Nonaka D, Priest L, Fusi A, Carlsson F, Carlsson A, Hendrix MJC, Seftor REB, Seftor EA, Rothwell DG, Hughes A, Hicks J, Miller C, Kuhn P, Brady G, Simpson KL, Blackhall FH, Dive C. Vasculogenic mimicry in small cell lung cancer. Nature Communications 2016;7:13322.

Carter LR, Rothwell DG, Leong H, Li Y, Burt DJ, Antonello J, Hodgkinson C, Morris K, Franklin L, Miller CJ, Blackhall F, Dive C, Brady G. Investigating chemoresistance in small cell lung cancer through the molecular profiling of single circulating tumour cells. Cancer Research 2016;76:3155.

Tape CJ, Ling S, Dimitriadi M, McMahon KM, Worboys JD, Leong HS, Norrie IC, Miller CJ, Poulogiannis G, Lauffenburger DA, Jørgensen C. Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation. Cell 2016;165:910-20.

Marusiak A, Stephenson N, Baik H, Trotter E, Li Y, Blyth K, Mason S, Chapman P, Puto LA, Read JA, Brassington C, Pollard HK, Phillips C, Green I, Overman R, Collier M, Testoni E, Miller C, Hunter T, Sansom OJ, Brognard J. Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis. Cancer Res. 2016;76:724-35.

Draper J, Sroczynska P, Tsoulaki O, Leong HS, Fadlullah MZH, Miller C, Kouskoff V, Lacaud G. RUNX1B Expression Is Highly Heterogeneous and Distinguishes Megakaryocytic and Erythroid Lineage Fate in Adult Mouse Hematopoiesis. PLoS Genetics 2016;12:e1005814.

Memon D, Dawson K, Smowton C, Xing W, Dive C, Miller C. Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response. Genomic Medicine 2016;1:16020.

Group Leader

A middle-aged man with short, light-coloured hair smiles warmly at the camera. He is wearing a black jumper over a white collared shirt, and the background is plain and light-coloured.

Crispin Miller*