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Nuno Morais Lab

Disease Transcriptomics

Nuno Morais Lab

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Nuno Barbosa-Morais

Group Leader

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Disease Transcriptomics

We are computational biologists applying bioinformatics approaches, particularly those involving the analysis of high-throughput genomic and transcriptomic data, to fundamental questions in biomedical research. We have a long-term interest in the systems-level transcriptional regulation underlying mammalian cell specification, often perturbed in disease. We aim to understand how RNA-level (transcription initiation, splicing, etc.) changes in (mostly) human tissues increase proneness to ageing-related diseases, namely cancer, and influence therapeutic responses. We are particularly interested in understanding the transcriptional mechanisms of human cells’ response to stress and unveiling their molecular signatures. We thereby aim to identify molecular targets for functional exploration in vitro and in vivo. We also combine molecular and clinical information for the unveiling of novel candidate prognostic factors and therapeutic targets. Along the way, we develop some tools for assisting non-computational scientists in their analyses of transcriptomic data.

Funders

RNA (de)regulation in human disease

The roles and respective molecular signatures of tumour-infiltrating myeloid cells in breast cancer at the single-cell level;
The phenotypic spectrum and therapeutic potential of macrophages in human diseases;
Common and specific transcriptomic markers of different types of cell stress and senescence and their regulation;
Intron retention a functional tuner of transcription in development and senescence;
Evolution of regulation and functionality of dual coding CDKN2A – implications in development, physiology, senescence, and cancer;
Transcriptional signatures of genotoxic stress resistance in colorectal cancer;
Circadian disruption in a submarine crew – the health impact of alternating shift work in low-light and confined environments.

Bioinformatics tools for the analysis of RNA-seq data

Graphical applications for alternative splicing quantification and analysis from RNA-seq data;
Identification of candidate causal genetic and chemical perturbations from differential gene expression data;
Web applications for assisting non-computational scientists in their analyses of single-cell RNA-seq data.

2024/2027: BIOMICS – Fostering Excellent Research, Training and Innovation in Biomedical Data Science; European Comission, Twinning GA 101159926

A. L. Schneider*, R. Martins-Silva*, A. Kaizeler*, N. Saraiva-Agostinho, N. L. Barbosa-Morais (2024). voyAGEr, free web interface for the analysis of age-related gene expression alterations in human tissues. eLife 12: RP88623. (*co-first authors).

M. Ascensão-Ferreira*, R. Martins-Silva*, N. Saraiva-Agostinho, N. L. Barbosa-Morais (2024). betAS: intuitive analysis and visualization of differential alternative splicing using beta distributions. RNA 30(4): 337–353. (*co-first authors).

M. C. Bordone, N. L. Barbosa-Morais (2020). Unraveling targetable systemic and cell-type-specific molecular phenotypes of Alzheimer’s and Parkinson’s brains with digital cytometry. Frontiers in Neuroscience 14: 607215.

O. M. Rathore, R. D. Silva, M. Ascensão-Ferreira, R. Matos, C. Carvalho, B. Marques, M. N. Tiago, P. Prudêncio, R. P. Andrade, J. Y. Roignant, N. L. Barbosa-Morais+, R. G. Martinho+ (2020). NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning. RNA 26(12): 1935–1956. (+corresponding authors).

N. Saraiva-Agostinho, N. L. Barbosa-Morais (2020). Interactive alternative splicing analysis of human stem cells using psichomics. Methods in Molecular Biology 2117: 179–205.

C. Godinho-Silva, R. G. Domingues, M. Rendas, B. Raposo, H. Ribeiro, J. A. da Silva, A. Vieira, R. M. Costa, N. L. Barbosa-Morais, T. Carvalho, H. Veiga-Fernandes (2019). Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis. Nature 574(7777): 254–258.

J. Munkley+, L. Ling, S. R. G. Krishnan, G. Hysenaj, E. Scott, C. Dalgliesh, H. Z. Oo, T. M. Maia, K. Cheung, I. Ehrmann, K. E. Livermore, H. Zielinska, O. Thompson, B. Knight, P. McCullagh, J. McGrath, M. Crundwell, L. W. Harries, M. Daugaard, S. Cockell, N. L. Barbosa-Morais+, S. Oltean+, D. J. Elliott+ (2019). Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer. eLife 8: e47678. doi: 10.7554/eLife.47678. (+corresponding authors).

B. P. de Almeida, A. F. Vieira, J. Paredes, M. Bettencourt-Dias, N. L. Barbosa-Morais (2019). Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome. PLoS Computational Biology 15(3): e1006832.

N. Saraiva-Agostinho, N. L. Barbosa-Morais (2019). psichomics: graphical application for alternative splicing quantification and analysis. Nucleic Acids Research 47(2): e7.

L. M. Gallego-Paez, M. C. Bordone, A. C. Leote, N. Saraiva-Agostinho, M. Ascensão-Ferreira, N. L. Barbosa-Morais (2017). Alternative splicing: the pledge, the turn and the prestige – The key role of alternative splicing in human biological systems. Human Genetics 136(9): 1015–1042.

Find a complete list of publications here.

2024: University of Lisbon / Caixa Geral de Depósitos Scientific Award in Biomedical Sciences.

2024: João Lobo Antunes Merit PhD Thesis Award [Nuno Agostinho].

2020-2026: FCT Scientific Employment Stimulus – Assistant Researcher.

2019: 1st prize, Young ICSA Poster Award, International Cell Senescence Association conference 2019 (Athens, Greece) [Mariana Ferreira].

2017: AstraZeneca Innovate Competition – Translational Research [Mariana Ferreira].

2015-2021: EMBO (European Molecular Biology Organization) Installation Grant.

2015-2019: FCT Investigator Starting Grant.

Disease Transcriptomics @ GIMM: https://imm.medicina.ulisboa.pt/group/distrans/

Disease Transcriptomics Lab @ Bluesky: https://bsky.app/profile/nmoraislab.bsky.social

BIOMICS – Fostering Excellent Research, Training and Innovation in Biomedical Data Science:
https://biomics.gimm.pt/

BIOMICS @ Bluesky: https://bsky.app/profile/biomics-twinning.bsky.social