Research Lab

Computational Multi-Omics

29685

Lab Members

Research Interests

Our mission is to understand the (epi)genome biology and its impact on pathological conditions using computational multi-omics approaches. Such methods rely on the statistical analysis and integration of big data (high-throughput sequencing, microarrays, proteomics, high-throughput screening) and clinical/phenotypic data.

The regulation of (epi)genome and transcriptome networks is a crucial component of a healthy cell, but it is relatively unknown the molecular mechanisms underlying its misregulation in diseases: from cancer to age-related disorders. We have been deciphering pathological conditions through multiomics approaches, identifying molecular events to be further used as biomarkers and therapeutic targets.

Research Highlights

Unveiling the complexity of cell biology and underlying disregulation of diseases by deciphering multi-omics data

Through muti-omics profiling of a prospective cohort of 136 colorectal tumor biopsies we unveiled that mutational and chromosomal instability concertedly shape genetic and microenvironmental tumor heterogeneity (Sobral et al 2022, Communications Biology). Moreover, we demonstrated that tumor heterogeneity can be a prognostic marker of tumor relapse, where clonal diversity driven by large copy number alterations favors metastatic potential and multiple events of metastatic seeding. Overall, our findings unveiled that clonal diversity can influence microenvironment heterogeneity, differing across colorectal tumor subtypes and influencing tumor evolution and metastasis progression.

Representative Projects

"The cell of origin of PDAC: novel opportunities for the early diagnosis and treatment of PDAC" - La Caixa, Total Funding 1M€. Unit Funding: 150.000 €. Ana Rita Grosso (PI) (2023-2026)
"Dissecting the molecular mechanisms of X-chromosome inactivation using human embryonic stem cells" - FCT-MTES, Total Funding 250.000€. Unit Funding 107.000€. Ana Rita Grosso (co-PI) (2022-2025)
“Decoding pseudogene transcriptional regulation during cell differentiation” – FCT-MCTES, Total and Unit Funding: € 50,000. Ana Rita Grosso (PI) (2015-2019)
“Targeting Intra-Tumor heterogeneity as a promising therapeutic strategy for cancer”, FCT-MTES, Total and Unit Funding € 239,478. Ana Rita Grosso, (PI) (2018-2022)

Selected Publications

Raposo, AC; Caldas, P; Jeremias, J; Arez, M; Mateus, FC; Barbosa, P; Sousa-Luís, R; Agua, F; Oxley, D; Mupo, A; Eckersley-Maslin, M; Casanova, M; Grosso, AR; da Rocha, ST. 2025. Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation. Stem Cell Reports, 20, DOI: 10.1016/j.stemcr.2025.102472

Kraft, M; Schoofs, H; Petkova, M; Andrade, J; Grosso, AR; Benedito, R; De Roo, AK; Boon, LM; Vikkula, M; Kapp, FG; Hägerling, R; Potente, M; Mäkinen, T. 2025. Angiopoietin-TIE2 feedforward circuit promotes PIK3CA-driven venous malformations. NATURE CARDIOVASCULAR RESEARCH, DOI: 10.1038/s44161-025-00655-9

Mafalda Soares; Inês Saraiva Wemans; Paulo Caldas; Simão Teixeira da Rocha; Ana Rita Grosso. 2025. X-linked transcriptome dysregulation across immune cells in systemic lupus erythematosus. Biology of Sex Differences, DOI: 10.1186/s13293-025-00750-3

Dantas, T; Abreu, CMC; De-Castro, MJG; Grosso, AR; Valente, JD; Xavier, GD. 2024. 25 de Abril Sempre! Portuguese Science and the 50th anniversary of the Carnation Revolution. Communications Biology, 7, DOI: 10.1038/s42003-024-06229-y

Gonçalves, C; Cabral, IM; de Matos, APA; Grosso, AR; Costa, PM. 2024. Transcriptome profiling of the posterior salivary glands of the cuttlefish <i>Sepia officinalis</i> from the Portuguese West coast. Frontiers in Marine Science, 11, DOI: 10.3389/fmars.2024.1362824