VHIO’s Cancer Computational Biology Group leverages large-scale genetic and epigenetic cancer datasets to elucidate the molecular mechanisms underlying tumor initiation, progression, drug resistance and , with the ultimate goal of improving patient outcomes.
Our research focuses on defining the role of chromatin regulatory elements in treatment response and metastatic progression, identifying epigenetic synthetic lethality-based therapeutic options, improving patient stratification through integrative multi-omics analyses, and discovering novel epigenetic biomarkers of therapeutic response. We have previously demonstrated how genetic modifiers of chromatin structure are associated with chemotherapy resistance in breast cancer (Seoane et al. 2019 , and we continue to investigate how epigenetic alterations drive drug resistance and how epigenetic therapies can be leveraged to reactivate tumor suppressor pathways.
In parallel, we develop machine learning approaches for the horizontal and vertical integration of multi-omics datasets to uncover previously unrecognized cancer subgroups, identify predictive biomarkers, and improve the prediction of treatment outcomes and drug response. Additionally, we are advancing epigenetic methodologies to infer past environmental exposures from tumor samples.
The group actively contributes to multiple international collaborative efforts, including The Cancer Genome Atlas, the Human Tumor Atlas Network, Cancer Target Discovery and Development (CTD 2) Network, and, most recently, AURORA (metastatic breast cancer multi-omics cohort), reinforcing its commitment to data-driven discovery and translational impact.
Figure: Integrative workflow for synthetic lethality discovery. The circular diagram illustrates the iterative process of SL identification, combining experimental and computational approaches. The computational half (right side) consists of data integration, computational modeling, prediction refinement, and new hypothesis generation, feeding back into experimental testing. This experimental half (left side) includes screening experiments, data collection & processing, validation and therapeutic design. The results obtained will be the computational method’s input.
- Understand the role of chromatin regulatory elements in treatment response and metastasis.
- Discover new epigenetic biomarkers of drug response.
- Potentiate therapeutic options by combining epigenetic therapies with other agents.
- Discover potential environmental causes of early onset cancer using epigenetic tools.
- Develop clinically actionable machine learning algorithms for prediction and patient stratification.
Group Leader
José Antonio Seoane
Post-Doctoral Fellow
Hubert Bretonniere
Lea Lemler
Silvana Maas
Graduate students
Mary Fariña
María Butjosa
Enric Álvarez,
Juan Rafael Valera
Arnau Llinàs
Xavier Viñas
Laia Ollé
Master’s Student
Núria Montalà
Most relevant scientific publications
- Farina-Morillas M, Ollé-Monràs L, Maas SC, de Rojas-P I, Segura MF, Seoane JA. Epigenetic synthetic lethality as a cancer therapeutic strategy: synergy of experimental and computational approaches. Epigenomics. 2025 Oct;17(15):1069-1081.
- Carra D, Maas SCE, Seoane JA, Alonso-Curbelo D. Exposomal determinants of non-genetic plasticity in tumor initiation. Trends Cancer. 2025 Apr;11(4):295-308.
- Llinas-Bertran A, Butjosa-Espín M, Barberi V, Seoane JA. Multimodal data integration in early-stage breast cancer. Breast. 2025 Apr;80:103892.
- Biagioni C, Fimereli D, Irrthum A, Guerrero-Zotano A, Piccart M, Cameron D, Caballero C, Raimbault A, Martins-Branco D, Romagnoli D, Agostinetto E, Venet D, Llinas-Bertran A, Seoane JA, Zoppoli G, Vivancos A, Vingiani A, Oliveira M, Curigliano G, Crestani T, Sotiriou C, Nili Gal-Yam E, Hilbers FS, Aftimos P, Benelli M. Molecular and clinical analyses of gene fusions identify therapeutic targets in paired primary and metastatic breast cancer from the AURORA program (BIG 14-01). Clin Cancer Res. 2025. doi: 10.1158/1078-0432.CCR-25-2707.
- Llinas-Bertran A, Bellet-Ezquerra M, Seoane JA. Epigenetic Control of Cancer Cell Dormancy and Awakening in Endocrine Therapy Resistance. Cancer Discov. 2024 May 1;14(5):704-706.
- Miera-Maluenda M, Pérez-Torres M, Mañas A, Rubio-San-Simón A, Butjosa-Espín M, Ruiz-Duran P, Seoane JA, Moreno L, Segura MF. Advances in the approaches used to repurpose drugs for neuroblastoma. Expert Opin Drug Discov. 2024 Nov;19(11):1309-1319.
- Salahudeen AA, Seoane JA, Yuki K, Mah AT, Smith AR, Kolahi K, De la O SM, Hart DJ, Ding J, Ma Z, Barkal SA, Shukla ND, Zhang CH, Cantrell MA, Batish A, Usui T, Root DE, Hahn WC, Curtis C, Kuo CJ. Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis. Cell Rep. 2023 Nov 28;42(11):113355.
- Kaiser AM, Gatto A, Hanson KJ, Zhao RL, Raj N, Ozawa MG, Seoane JA, Bieging-Rolett KT, Wang M, Li I, Trope WL, Liou DZ, Shrager JB, Plevritis SK, Newman AM, Van Rechem C, Attardi LD. p53 governs an AT1 differentiation programme in lung cancer suppression. Nature. 2023 Jul;619(7971):851-859.
- Strand SH, Rivero-Gutiérrez B, Houlahan KE, Seoane JA, King LM, Risom T, Simpson LA, Vennam S, Khan A, Cisneros L, Hardman T, Harmon B, Couch F, Gallagher K, Kilgore M, Wei S, DeMichele A, King T, McAuliffe PF, Nangia J, Lee J, Tseng J, Storniolo AM, Thompson AM, Gupta GP, Burns R, Veis DJ, DeSchryver K, Zhu C, Matusiak M, Wang J, Zhu SX, Tappenden J, Ding DY, Zhang D, Luo J, Jiang S, Varma S, Anderson L, Straub C, Srivastava S, Curtis C, Tibshirani R, Angelo RM, Hall A, Owzar K, Polyak K, Maley C, Marks JR, Colditz GA, Hwang ES, West RB. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts. Cancer Cell . 2022 Dec 12;40(12):1521-1536.e7.
- Nobre AR, Dalla E, Yang J, Huang X, Wullkopf L, Risson E, Razghandi P, Anton ML, Zheng W, Seoane JA, Curtis C, Kenigsberg E, Wang J, Aguirre-Ghiso JA. ZFP281 drives a mesenchymal-like dormancy program in early disseminated breast cancer cells that prevents metastatic outgrowth in the lung. Nat Cancer . 2022 Oct;3(10):1165-1180.
- Raj N, Wang M, Seoane JA, Zhao RL, Kaiser AM, Moonie NA, Demeter J, Boutelle AM, Kerr CH, Mulligan AS, Moffatt C, Zeng SX, Lu H, Barna M, Curtis C, Chang HY, Jackson PK, Attardi LD. The Mettl3 epitranscriptomic writer amplifies p53 stress responses. Mol Cell . 2022 Jul 7;82(13):2370-2384.e10.
- Liñares-Blanco J, Fernandez-Lozano C, Seoane JA, López-Campos G. Machine Learning Based Microbiome Signature to Predict Inflammatory Bowel Disease Subtypes. Front Microbiol . 2022 May 17;13:872671..
- DCIS genomic signatures define biology and correlate with clinical outcome: a Human Tumor Atlas Network (HTAN) analysis of TBCRC 038 and RAHBT cohorts
Siri H Strand, Belén Rivero-Gutiérrez, Kathleen E Houlahan, Jose A Seoane, Lorraine King, …,Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R Marks, Graham A Colditz, E Shelley Hwang, Robert B West
bioRxiv, Jun 2021
10.1101/2021.06.16.448585 - CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities
Kyuho Han, Sarah E Pierce, Amy Li, Kaitlyn Spees, Grace R Anderson, Jose A Seoane, Yuan-Hung Lo, Michael Dubreuil, Micah Olivas, Roarke A Kamber, Michael Wainberg, Kaja Kostyrko, Marcus R Kelly, Maryam Yousefi, Scott W Simpkins, David Yao, Keonil Lee, Calvin J Kuo, Peter K Jackson, Alejandro Sweet-Cordero, Anshul Kundaje, Andrew J Gentles, Christina Curtis, Monte M Winslow, Michael C Bassik
Nature, 580(7801):136-141, April. 2020 - Convergent mutations in tissue-specific regulatory regions reveal novel cancer drivers
Nasa Sinnott-Armstrong, Jose A Seoane, Jonathan K Pritchard, Christina Curtis, Michael P Snyder
BioRxiv, Nov. 2020 - Chromatin regulators mediate anthracycline sensitivity in breast cancer
Jose A Seoane, Jacob G Kirkland, Jennifer L Caswell-Jin, Gerald R Crabtree, Christina Curtis
Nature medicine, 25(11):1721-1727, Nov. 2019 - Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups
Oscar M Rueda, Stephen-John Sammut, Jose A Seoane, Suet-Feung Chin, Jennifer L Caswell-Jin, Maurizio Callari, Rajbir Batra, Bernard Pereira, Alejandra Bruna, H Raza Ali, Elena Provenzano, Bin Liu, Michelle Parisien, Cheryl Gillett, Steven McKinney, Andrew R Green, Leigh Murphy, Arnie Purushotham, Ian O Ellis, Paul D Pharoah, Cristina Rueda, Samuel Aparicio, Carlos Caldas, Christina Curtis
Nature, 567(7748):399-404, Mar. 2019 - Assessment of ERBB2/HER2 status in HER2-equivocal breast cancers by FISH and 2013/2014 ASCO-CAP guidelines
Michael F Press, Jose A Seoane, Christina Curtis, Emmanuel Quinaux, Roberta Guzman, Guido Sauter, Wolfgang Eiermann, John R Mackey, Nicholas Robert, Tadeusz Pienkowski, John Crown, Miguel Martin, Vicente Valero, Valerie Bee, Yanling Ma, Ivonne Villalobos, Dennis J Slamon
JAMA oncology, 5(3):366-375, Mar. 2019 - The chromatin accessibility landscape of primary human cancers
M Ryan Corces, Jeffrey M Granja, Shadi Shams, Bryan H Louie, Jose A Seoane, Wanding Zhou, Tiago C Silva, Clarice Groeneveld, Christopher K Wong, Seung Woo Cho, Ansuman T Satpathy, Maxwell R Mumbach, Katherine A Hoadley, A Gordon Robertson, Nathan C Sheffield, Ina Felau, Mauro AA Castro, Benjamin P Berman, Louis M Staudt, Jean C Zenklusen, Peter W Laird, Christina Curtis, William J Greenleaf, Howard Y Chang
Science, 362(6413), Oct. 2018 - Canonical correlation analysis for gene-based pleiotropy discovery
Jose A Seoane, Colin Campbell, Ian NM Day, Juan P Casas, Tom R Gaunt
PLoS Computational Biology, 10(10), Oct. 2014 - A pathway-based data integration framework for prediction of disease progression
Jose A Seoane, Ian NM Day, Tom R Gaunt, Colin Campbell
Bioinformatics, 30(6):838-845, Mar. 2014
- Characterizing Heterogeneous Regulatory prOgraMs in ER+ breast cancer (CHROME). Funded by: Agencia Estatal de Investigación – Ministerio de Ciencia e Innovación. Reference: PID2024-162678OB-I00. Execution period: 01/09/2025 – 31/08/2028. PI: José Antonio Seoane
- Targeting synthetic lethality in Chromatin Regulatory Genes for gastrointestinal cancer treatment. Ref PID2020-115097RA-I00.
Agencia Estatal de Investigación. 9/2021-8/2025. PI: Jose A. Seoane
- Ramon y Cajal Grant.
Agencia Estatal de Investigación. 2021-2025 - Epigenetic differences associated with hormone treatment resistant breast cancer heterogeneity Fundación FERO. 2022-2024
- Identificación in Silico de Respuesta a fármacos especifica de metastasis
Entidad Financiadora: MCIN/AEI/10.13039/501100011033Ref: CNS2022-135424Periodo de Ejecución: 01/09/2023 – 31/12/2026. PI: Jose Antonio Seoane
Grant funded by the European Union NextGenerationEU/Plan de Recuperación, Transformación y Resilencia (PRTR) - TACTIC: Explorando soluciones a los retos de salud mediante ciencia disruptiva, terapias avanzadas y medicina de sistemas. Programa FORTALECE ISCIII REF: FORT23/00034. 2024-2027
- Our group was awarded a LAB AECC grant by the Scientific Foundation of the Spanish Association Against Cancer (Asociación Española Contra el Cáncer – AECC), to study the subtypes of BRAF mutant colorectal cancer (CRC).
- In 2025, we welcomed Xavi Viñas and Núria Montalà to our team.
- Silvana Maas presented our exposome work at the American Association for Cancer Research (AACR) Special Conference in Cancer Research: The Rise in Early-Onset Cancers— Knowledge Gats and Research Opportunities, 10 – 13 December, Montreal, Canada, and the European Association for Cancer Research (EACR) – Mark Foundation Joint Conference: The Rise of Early-Onset Cancers – Biology, Causes and Detection, 11 – 13 November, Bergamo, Italy.
This group is supported by CaixaResearch
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