Evolution of new genes
We are investigating the mechanisms by which new genes originate with a special emphasis on genes originated de novo from previously non-coding genomic regions. The research is strongly based on the analysis of transcriptomics and translatomics (RiboSeq) data from related species and individuals. We are examining different model systems, including human cell lines and yeast isolates. Additionally, we are taking advantage of long read transcriptomics technologies to learn about the changes in gene structure and expression across evolutionary time. Research in this area is currently supported by an European Research Council Advanced Grant (NovoGenePop) and a grant from the Spanish Ministry of Science and Innovation (PID2021-122726NB-I00).
Collaborators: Lucas Wange (UPF/IMIM), Tomàs Marqués-Bonet (UPF), Elena Hidalgo (UPF), Xavier Messeguer (UPC), Joseph Schacherer (University of Strasbourg).
Recent publications:
Montañés, J.C., Huertas, M., Messeguer, X., Albà, M.M. (2023). Evolutionary trajectories of new duplicated and putative de novo genes. Molecular Biology and Evolution, 40(5):msad098.
Blevins, W.R., Ruiz-Orera, J., Messeguer, X., Blasco-Moreno, B., Villanueva-Cañas, J-L., Espinar, L., Díez, J., Carey, L.B., Albà, M.M. (2021). Uncovering de novo gene birth in yeast using deep transcriptomics. Nature Communications 12:604.
Ruiz-Orera, J., Albà, M.M. (2019). Translation of small open reading frames: roles in regulation and evolutionary innovation. Trends in Genetics 35: 186-198.
Ruiz-Orera, J., Verdaguer-Grau, P., Villanueva-Cañas, J-l., Messeguer, X., Albà, M.M. (2018). Translation of neutrally evolving peptides provides a basis for de novo gene evolution. Nature Ecology and Evolution 2:890-896.
Villanueva-Cañas, J-L. Ruiz-Orera, J., M.I., Gallo, M., Andreu, D., Albà, M.M. (2017) New genes and functional innovation in mammals. Genome Biology and Evolution 9: 1886–1900.
Ruiz-Orera, J., Hernandez-Rodriguez, J., Chiva, C., Sabidó, E., Kondova, I., Bontrop, R., Marqués-Bonet, T., Albà, M.M (2015) Origins of de novo genes in human and chimpanzee. Plos Genetics, 11 (12), pp. e1005721.
Ruiz-Orera, J., Messeguer, X., Subirana J.A., Albà M.M. (2014) Long non-coding RNAs as a source of new peptides. eLife, 3:e03523.
The neoantigen landscape of cancer cells
We are investigating how the accumulation of mutations during cancer progression, as well as the translation of non-canonical ORFs in cancer-specific transcripts, can result in the production of neoantigens with the capacity to trigger an immune response against the cancer cells. We are also developing machine learning methods to improve the prediction of the response to immunotherapy using extensive whole exome sequencing and transcriptomics data. This research is funded by the BBVA Foundation and the Institute of Health Carlos III (Spanish Government).
Collaborators: Júlia Perera-Bel (IMIM), Robert Castelo (UPF), Joaquim Bellmunt (IMIM/Harvard), Puri Fortes (UNAV).
Recent publications:
Boll, L.*, Perera-Bel, J.*, Rodríguez-Vida, A., Arpí, O., Rovira, A., Juanpere, N., Vázquez, S., Hernández-Llodrà, S., Lloreta, J., Albà, M.M.#, Bellmunt, J.#. (2023) The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer. Scientific Reports 13:15287. *co-first, #co-corresponding
Camarena, M.E., Theunissen, P., Ruiz, M., Ruiz-Orera, J., Calvo-Serra, B., Castelo, R., Castro, C., Sarobe, P., Fortes, P.* , Perera-Bel, J.* , Albà, M.M.* (2024) Non-canonical ORFs are an important source of tumor-specific antigens in a liver cancer meta-cohort. Science Advances 10:eadn3628 *co-corresponding
Boll, L.*, Vázquez, S.*, Camarena, M.E., Castelo, R., Bellmunt, J.#, Perera-Bel, J.#, Albà, M.M.# (2024) Predicting immunotherapy response in advanced bladder cancer: a meta-analysis of six independent cohorts. bioRxiv, April 22 2024. https://www.biorxiv.org/content/10.1101/2024.04.18.589711v1. *co-first, #co-corresponding