Introduction to data in cancer
The Cancer Computational Biology group leverage epi(genetic) cancer datasets in order to discover the molecular mechanism related with cancer initiation, progression, drug resistance and metastasis in order to improve patient perspectives.
We have shown how the genes that modify the chromatin structure are associated with chemotherapy resistance in breast cancer (Nature Medicine, 2019). We are interested in understanding how these epigenetic modifications affect drug resistance and how epigenetic drugs can be used to target tumor suppressor genes.
We are also interested in machine learning based integration of multi-omic datasets in order to discover new cancer subgroups and biomarkers, and prediction of outcome and drug response.
We have participated in multiple international consortiums including The Cancer Genome Atlas, Human Tumor Atlas Network, Cancer Target Discovery and Development and recently and recently AURORA (Metastatic breast cancer multi-omic cohort)
- Understand the role of chromatin regulatory elements in drug response and metastasis
- Discover new epigenetic synthetic lethality based therapeutic options
- Patient stratification using multi-omic analysis
- Discover new epigenetic biomarkers of drug response
José Antonio Seoane
Mª José Fariña
- 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
- 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
- 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.
- Cancer Computational Biology Lab at VHIO starts at May 2021
- Jose A. Seoane starts his Ramon y Cajal grant
- Jose A. Seoane receives a grant from the Ministerio de Ciencia e Innovación to explore epigenetic synthetic lethality mechanism
- Joins to AURORA metastatic breast cancer consortium
- José Liñares received his PhD in December
Chromatin regulatory genes, including chromatin and histone modifiers, are key players in cancer development. As an example, members of SWI/SNF complex have a mutation frequency (as a complex) ~20%, similar to TP53. Our main research line is the integration of several layers of (epi) genetic data obtained from TCGA, ICGC, GENIE, MSK-Impact, ENCODE, ROADMAP and others in order to discover how these chromatin regulatory genes modify the processes of grow, invasion, drug resistance and metastasis. Examples of this research are the discovery of how chromatin regulatory genes modify the sensitivity to anthracyclines in early stage breast cancer (Nature Medicine 2019). The development of a gene expression signature using this set of genes will allow to identify which woman will benefit of this therapy. This has very important implications: first, 6 months of adjuvant anthracycline-based chemotherapy reduces the annual breast cancer death rate by 38% for women younger than 50 years and 20% for women aged 50 to 69 years, so the identification of the woman resistant to this therapy could boost these percentages, and second, anthracyclines are highly toxic (related with cardiotoxicity and risk of secondary malignancies), so the identification of resistant women will avoid to expose these women to serious secondary effects.
In breast cancer we also found, in collaboration with Howard Chang lab, two mechanism of dysregulation of a SWF/SNF member BCL11A in breast cancer. It was reported that this gene was frequently copy number amplified in a subset of basal breast cancer. Using TCGA ATAC-Seq data we found that there is also high accessibility in several enhancer in basal breast cancer. But, using methylation data, we found that luminal breast cancer has hypermethylation in the promoter of BCL11A, which epigenetically silence the gene expression. Both alterations are associated with worst outcome.
We also found a hypermethylation in the promoter of BAZ2B, member of ISWI complex, which also reduce the expression. This event increase the expression of genes related with metastatic pathways and reduce expression in PRC2 genes. Methylation on this gene is associated with Stage IV and worse outcome (co-first author manuscript in preparation).
This group is supported by CaixaResearch