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Publicações

Publicações por Nuno Fonseca

2013

The Drosophila melanogaster methuselah Gene: A Novel Gene with Ancient Functions

Autores
Araujo, AR; Reis, M; Rocha, H; Aguiar, B; Morales Hojas, R; Macedo Ribeiro, S; Fonseca, NA; Reboiro Jato, D; Reboiro Jato, M; Fdez Riverola, F; Vieira, CP; Vieira, J;

Publicação
PLOS ONE

Abstract
The Drosophila melanogaster G protein-coupled receptor gene, methuselah (mth), has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although mth belongs to a gene subfamily with 16 members in D. melanogaster, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits. Here, we explore the alternative hypothesis that mth is an old gene. Under this hypothesis, in species distantly related to D. melanogaster, there should be a gene with features similar to those of mth. By performing detailed phylogenetic, synteny, protein structure, and gene expression analyses we show that the D. virilis GJ12490 gene is the orthologous of mth in species distantly related to D. melanogaster. We also show that, in D. americana (a species of the virilis group of Drosophila), a common amino acid polymorphism at the GJ12490 orthologous gene is significantly associated with developmental time, size, and lifespan differences. Our results imply that GJ12490 orthologous genes are candidates for developmental time and lifespan differences in Drosophila in general.

2016

Expression Atlas update - an integrated database of gene and protein expression in humans, animals and plants

Autores
Petryszak, R; Keays, M; Tang, YA; Fonseca, NA; Barrera, E; Burdett, T; Füllgrabe, A; Pomer Fuentes, AM; Jupp, S; Koskinen, S; Mannion, O; Huerta, L; Megy, K; Snow, C; Williams, E; Barzine, M; Hastings, E; Weisser, H; Wright, J; Jaiswal, P; Huber, W; Choudhary, J; Parkinson, HE; Brazma, A;

Publicação
Nucleic Acids Research

Abstract
Expression Atlas (http://www.ebi.ac.uk/gxa) provides information about gene and protein expression in animal and plant samples of different cell types, organism parts, developmental stages, diseases and other conditions. It consists of selected microarray and RNA-sequencing studies from Array Express, which have been manually curated, annotated with ontology terms, checked for high quality and processed using standardised analysis methods. Since the last update, Atlas has grown sevenfold (1572 studies as of August 2015), and incorporates baseline expression profiles of tissues from Human Protein Atlas, GTEx and FANTOM5, and of cancer cell lines from ENCODE, CCLE and Genentech projects. Plant studies constitute a quarter of Atlas data. For genes of interest, the user can view baseline expression in tissues, and differential expression for biologically meaningful pairwise comparisons-estimated using consistent methodology across all of Atlas. Our first proteomics study in human tissues is now displayed alongside transcriptomics data in the same tissues. Novel analyses and visualisations include: 'enrichment' in each differential comparison of GO terms, Reactome, Plant Reactome pathways and InterPro domains; hierarchical clustering (by baseline expression) of most variable genes and experimental conditions; and, for a given gene-condition, distribution of baseline expression across biological replicates. © The Author(s) 2015.

2014

AND Parallelism for ILP: The APIS System

Autores
Camacho, R; Ramos, R; Fonseca, NA;

Publicação
INDUCTIVE LOGIC PROGRAMMING: 23RD INTERNATIONAL CONFERENCE

Abstract
Inductive Logic Programming (ILP) is a well known approach to Multi-Relational Data Mining. ILP systems may take a long time for analyzing the data mainly because the search (hypotheses) spaces are often very large and the evaluation of each hypothesis, which involves theorem proving, may be quite time consuming in some domains. To address these efficiency issues of ILP systems we propose the APIS (And ParallelISm for ILP) system that uses results from Logic Programming AND-parallelism. The approach enables the partition of the search space into sub-spaces of two kinds: sub-spaces where clause evaluation requires theorem proving; and sub-spaces where clause evaluation is performed quite efficiently without resorting to a theorem prover. We have also defined a new type of redundancy (Coverage-equivalent redundancy) that enables the prune of significant parts of the search space. The new type of pruning together with the partition of the hypothesis space considerably improved the performance of the APIS system. An empirical evaluation of the APIS system in standard ILP data sets shows considerable speedups without a lost of accuracy of the models constructed.

2018

Expression Atlas: gene and protein expression across multiple studies and organisms

Autores
Papatheodorou, I; Fonseca, NA; Keays, M; Tang, YA; Barrera, E; Bazant, W; Burke, M; Füllgrabe, A; Pomer Fuentes, AM; George, N; Huerta, L; Koskinen, S; Mohammed, S; Geniza, MJ; Preece, J; Jaiswal, P; Jarnuczak, A; Huber, W; Stegle, O; Vizcaíno, JA; Brazma, A; Petryszak, R;

Publicação
Nucleic Acids Research

Abstract
Expression Atlas (http://www.ebi.ac.uk/gxa) is an added value database that provides information about gene and protein expression in different species and contexts, such as tissue, developmental stage, disease or cell type. The available public and controlled access data sets from different sources are curated and re-analysed using standardized, open source pipelines and made available for queries, download and visualization. As of August 2017, Expression Atlas holds data from 3,126 studies across 33 different species, including 731 from plants. Data from large-scale RNA sequencing studies including Blueprint, PCAWG, ENCODE, GTEx and HipSci can be visualized next to each other. In Expression Atlas, users can query genes or gene-sets of interest and explore their expression across or within species, tissues, developmental stages in a constitutive or differential context, representing the effects of diseases, conditions or experimental interventions. All processed data matrices are available for direct download in tab-delimited format or as R-data. In addition to the web interface, data sets can now be searched and downloaded through the Expression Atlas R package. Novel features and visualizations include the on-the-fly analysis of gene set overlaps and the option to view gene co-expression in experiments investigating constitutive gene expression across tissues or other conditions. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

2014

Expression Atlas update-a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments

Autores
Petryszak, R; Burdett, T; Fiorelli, B; Fonseca, NA; Gonzalez Porta, M; Hastings, E; Huber, W; Jupp, S; Keays, M; Kryvych, N; McMurry, J; Marioni, JC; Malone, J; Megy, K; Rustici, G; Tang, AY; Taubert, J; Williams, E; Mannion, O; Parkinson, HE; Brazma, A;

Publicação
NUCLEIC ACIDS RESEARCH

Abstract
Expression Atlas (http://www.ebi.ac.uk/gxa) is a value-added database providing information about gene, protein and splice variant expression in different cell types, organism parts, developmental stages, diseases and other biological and experimental conditions. The database consists of selected high-quality microarray and RNA-sequencing experiments from ArrayExpress that have been manually curated, annotated with Experimental Factor Ontology terms and processed using standardized microarray and RNA-sequencing analysis methods. The new version of Expression Atlas introduces the concept of 'baseline' expression, i.e. gene and splice variant abundance levels in healthy or untreated conditions, such as tissues or cell types. Differential gene expression data benefit from an in-depth curation of experimental intent, resulting in biologically meaningful 'contrasts', i.e. instances of differential pairwise comparisons between two sets of biological replicates. Other novel aspects of Expression Atlas are its strict quality control of raw experimental data, up-to-date RNA-sequencing analysis methods, expression data at the level of gene sets, as well as genes and a more powerful search interface designed to maximize the biological value provided to the user.

2013

Patterns of evolution at the gametophytic self-incompatibility Sorbus aucuparia (Pyrinae) S pollen genes support the non-self recognition by multiple factors model

Autores
Aguiar, B; Vieira, J; Cunha, AE; Fonseca, NA; Reboiro Jato, D; Reboiro Jato, M; Fdez Riverola, F; Raspe, O; Vieira, CP;

Publicação
JOURNAL OF EXPERIMENTAL BOTANY

Abstract
S-RNase-based gametophytic self-incompatibility evolved once before the split of the Asteridae and Rosidae. In Prunus (tribe Amygdaloideae of Rosaceae), the self-incompatibility S-pollen is a single F-box gene that presents the expected evolutionary signatures. In Malus and Pyrus (subtribe Pyrinae of Rosaceae), however, clusters of F-box genes (called SFBBs) have been described that are expressed in pollen only and are linked to the S-RNase gene. Although polymorphic, SFBB genes present levels of diversity lower than those of the S-RNase gene. They have been suggested as putative S-pollen genes, in a system of non-self recognition by multiple factors. Subsets of allelic products of the different SFBB genes interact with non-self S-RNases, marking them for degradation, and allowing compatible pollinations. This study performed a detailed characterization of SFBB genes in Sorbus aucuparia (Pyrinae) to address three predictions of the non-self recognition by multiple factors model. As predicted, the number of SFBB genes was large to account for the many S-RNase specificities. Secondly, like the S-RNase gene, the SFBB genes were old. Thirdly, amino acids under positive selectionuthose that could be involved in specificity determinationuwere identified when intra-haplotype SFBB genes were analysed using codon models. Overall, the findings reported here support the non-self recognition by multiple factors model.

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