2018
Authors
Ferreira, PG; Munoz Aguirre, M; Reverter, F; Sa Godinho, CPS; Sousa, A; Amadoz, A; Sodaei, R; Hidalgo, MR; Pervouchine, D; Carbonell Caballero, J; Nurtdinov, R; Breschi, A; Amador, R; Oliveira, P; Cubuk, C; Curado, J; Aguet, F; Oliveira, C; Dopazo, J; Sammeth, M; Ardlie, KG; Guigo, R;
Publication
NATURE COMMUNICATIONS
Abstract
Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante-and postmortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.
2018
Authors
Amendola, L; Appleby, S; Avgoustidis, A; Bacon, D; Baker, T; Baldi, M; Bartolo, N; Blanchard, A; Bonvin, C; Borgani, S; Branchini, E; Burrage, C; Camera, S; Carbone, C; Casarini, L; Cropper, M; de Rham, C; Dietrich, JP; Di Porto, C; Durrer, R; Ealet, A; Ferreira, PG; Finelli, F; Garcia Bellido, J; Giannantonio, T; Guzzo, L; Heavens, A; Heisenberg, L; Heymans, C; Hoekstra, H; Hollenstein, L; Holmes, R; Hwang, ZQ; Jahnke, K; Kitching, TD; Koivisto, T; Kunz, M; La Vacca, G; Linder, E; March, M; Marra, V; Martins, C; Majerotto, E; Markovic, D; Marsh, D; Marulli, F; Massey, R; Mellier, Y; Montanari, F; Mota, DF; Nunes, NJ; Percival, W; Pettorino, V; Porciani, C; Quercellini, C; Read, J; Rinaldi, M; Sapone, D; Sawicki, I; Scaramella, R; Skordis, C; Simpson, F; Taylor, A; Thomas, S; Trotta, R; Verde, L; Vernizzi, F; Vollmer, A; Wang, Y; Weller, J; Zlosnik, T;
Publication
LIVING REVIEWS IN RELATIVITY
Abstract
Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015-2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid's Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
2021
Authors
Baptista, D; Ferreira, PG; Rocha, M;
Publication
BRIEFINGS IN BIOINFORMATICS
Abstract
2020
Authors
Sousa, A; Ferreira, M; Oliveira, C; Ferreira, PG;
Publication
FRONTIERS IN GENETICS
Abstract
Cancer has an important and considerable gender differential susceptibility confirmed by several epidemiological studies. Gastric (GC) and thyroid cancer (TC) are examples of malignancies with a higher incidence in males and females, respectively. Beyond environmental predisposing factors, it is expected that gender-specific gene deregulation contributes to this differential incidence. We performed a detailed characterization of the transcriptomic differences between genders in normal and tumor tissues from stomach and thyroid using Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) data. We found hundreds of sex-biased genes (SBGs). Most of the SBGs shared by normal and tumor belong to sexual chromosomes, while the normal and tumor-specific tend to be found in the autosomes. Expression of several cancer-associated genes is also found to differ between sexes in both types of tissue. Thousands of differentially expressed genes (DEGs) between paired tumor-normal tissues were identified in GC and TC. For both cancers, in the most susceptible gender, the DEGs were mostly under-expressed in the tumor tissue, with an enrichment for tumor-suppressor genes (TSGs). Moreover, we found gene networks preferentially associated to males in GC and to females in TC and correlated with cancer histological subtypes. Our results shed light on the molecular differences and commonalities between genders and provide novel insights in the differential risk underlying these cancers.
2020
Authors
The GTEx Consortium; Dias Ferreira, PG;
Publication
Science
Abstract
2020
Authors
Teles, SP; Oliveira, P; Ferreira, M; Carvalho, J; Ferreira, P; Oliveira, C;
Publication
CANCERS
Abstract
Gastric Cancer (GC) is one of the most common and deadliest types of cancer in the world. To improve GC prognosis, increasing efforts are being made to develop new targeted therapies. Although FGFR2 genetic amplification and protein overexpression in GC have been targeted in clinical trials, so far no improvement in patient overall survival has been found. To address this issue, we studied genetic and epigenetic events affecting FGFR2 and its splicing regulator ESRP1 in GC that could be used as new therapeutic targets or predictive biomarkers. We performed copy number variation (CNV), DNA methylation, and RNA expression analyses of FGFR2/ESRP1 across several cohorts. We discovered that both genes were frequently amplified and demethylated in GC, resulting in increased ESRP1 expression and of a specific FGFR2 isoform: FGFR2-IIIb. We also showed that ESRP1 amplification in GC correlated with a significant decreased expression of FGFR2-IIIc, an alternative FGFR2 splicing isoform. Furthermore, when we performed a survival analysis, we observed that patients harboring diffuse-type tumors with low FGFR2-IIIc expression revealed a better overall survival than patients with FGFR2-IIIc high-expressing diffuse tumors. Our results encourage further studies on the role of ESRP1 in GC and support FGFR2-IIIc as a relevant biomarker in GC.
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