Cookies Policy
The website need some cookies and similar means to function. If you permit us, we will use those means to collect data on your visits for aggregated statistics to improve our service. Find out More
Accept Reject
  • Menu
Publications

Publications by Nuno Fonseca

2017

Online resources for PCAWG data exploration, visualization, and discovery

Authors
Goldman, M; Zhang, J; Fonseca, NA; Xiang, Q; Craft, B; Piñeiro-Yáñez, E; O'Connor, B; Bazant, W; Barrera, E; Muñoz, A; Petryszak, R; Füllgrabe, A; Al-Shahrour, F; Keays, M; Haussler, D; Weinstein, J; Huber, W; Valencia, A; Papatheodorou, I; Zhu, J; Ferreti, V; Vazquez, M; PCAWG-12 Working Group,; PCAWG Network,;

Publication

Abstract
The Pan-Cancer Analysis of Whole Genomes (PCAWG) cohort provides a large, uniformly-analyzed, whole-genome dataset. The PCAWG Landing Page (http://docs.icgc.org/pcawg) focuses on four biologist-friendly, publicly-available web tools for exploring this data: The ICGC Data Portal, UCSC Xena, Expression Atlas, and PCAWG-Scout. They enable researchers to dynamically query the complex genomics data, explore tumors' molecular landscapes, and include external information to facilitate interpretation.

2017

Assessing the Gene Regulatory Landscape in 1,188 Human Tumors

Authors
Calabrese, C; Lehmann, K; Urban, L; Liu, F; Erkek, S; Fonseca, N; Kahles, A; Kilpinen-Barrett, LH; Markowski, J; Waszak, S; Korbel, J; Zhang, Z; Brazma, A; Raetsch, G; Schwarz, R; Stegle, O; PCAWG-3,;

Publication

Abstract
Cancer is characterised by somatic genetic variation, but the effect of the majority of non-coding somatic variants and the interface with the germline genome are still unknown. We analysed the whole genome and RNA-seq data from 1,188 human cancer patients as provided by the Pan-cancer Analysis of Whole Genomes (PCAWG) project to map cis expression quantitative trait loci of somatic and germline variation and to uncover the causes of allele-specific expression patterns in human cancers. The availability of the first large-scale dataset with both whole genome and gene expression data enabled us to uncover the effects of the non-coding variation on cancer. In addition to confirming known regulatory effects, we identified novel associations between somatic variation and expression dysregulation, in particular in distal regulatory elements. Finally, we uncovered links between somatic mutational signatures and gene expression changes, including TERT and LMO2, and we explained the inherited risk factors in APOBEC-related mutational processes. This work represents the first large-scale assessment of the effects of both germline and somatic genetic variation on gene expression in cancer and creates a valuable resource cataloguing these effects.

2017

Comprehensive genome and transcriptome analysis reveals genetic basis for gene fusions in cancer

Authors
Fonseca, NA; He, Y; Greger, L; Brazma, A; Zhang, Z; - PCAWG-3,;

Publication

Abstract
Gene fusions are an important class of cancer-driving events with therapeutic and diagnostic values, yet their underlying genetic mechanisms have not been systematically characterized. Here by combining RNA and whole genome DNA sequencing data from 1188 donors across 27 cancer types we obtained a list of 3297 high-confidence tumour-specific gene fusions, 82% of which had structural variant (SV) support and 2372 of which were novel. Such a large collection of RNA and DNA alterations provides the first opportunity to systematically classify the gene fusions at a mechanistic level. While many could be explained by single SVs, numerous fusions involved series of structural rearrangements and thus are composite fusions. We discovered 75 fusions of a novel class of inter-chromosomal composite fusions, termed bridged fusions, in which a third genomic location bridged two different genes. In addition, we identified 522 fusions involving non-coding genes and 157 ORF-retaining fusions, in which the complete open reading frame of one gene was fused to the UTR region of another. Although only a small proportion (5%) of the discovered fusions were recurrent, we found a set of highly recurrent fusion partner genes, which exhibited strong 5' or 3' bias and were significantly enriched for cancer genes. Our findings broaden the view of the gene fusion landscape and reveal the general properties of genetic alterations underlying gene fusions for the first time.

2015

Convergent Evolution at the Gametophytic Self-Incompatibility System in Malus and Prunus

Authors
Aguiar, B; Vieira, J; Cunha, AE; Fonseca, NA; Iezzoni, A; van Nocker, S; Vieira, CP;

Publication
PLOS ONE

Abstract
S-RNase-based gametophytic self-incompatibility (GSI) has evolved once before the split of the Asteridae and Rosidae. This conclusion is based on the phylogenetic history of the S-RNase that determines pistil specificity. In Rosaceae, molecular characterizations of Prunus species, and species from the tribe Pyreae (i.e., Malus, Pyrus, Sorbus) revealed different numbers of genes determining S-pollen specificity. In Prunus only one pistil and pollen gene determine GSI, while in Pyreae there is one pistil but multiple pollen genes, implying different specificity recognition mechanisms. It is thus conceivable that within Rosaceae the genes involved in GSI in the two lineages are not orthologous but possibly paralogous. To address this hypothesis we characterised the S-RNase lineage and S-pollen lineage genes present in the genomes of five Rosaceae species from three genera: M. x domestica (apple, self-incompatible (SI); tribe Pyreae), P. persica (peach, self-compatible (SC); Amygdaleae), P. mume (mei, SI; Amygdaleae), Fragaria vesca (strawberry, SC; Potentilleae), and F. nipponica (mori-ichigo, SI; Potentilleae). Phylogenetic analyses revealed that the Malus and Prunus S-RNase and S-pollen genes belong to distinct gene lineages, and that only Prunus S-RNase and SFB-lineage genes are present in Fragaria. Thus, S-RNase based GSI system of Malus evolved independently from the ancestral system of Rosaceae. Using expression patterns based on RNA-seq data, the ancestral S-RNase lineage gene is inferred to be expressed in pistils only, while the ancestral S-pollen lineage gene is inferred to be expressed in tissues other than pollen.

  • 20
  • 20