Biology subjects

Gonzalez-Perez, A.

Publications and source records attributed to Gonzalez-Perez, A..

4 recordsLinked to original sources

bioRxiv2018

Genome Wide Meta-Analysis identifies new loci associated with cardiac phenotypes and uncovers a common genetic signature shared by heart function and Alzheimer’s disease

AimsEchocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures of heart structure and functions have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with indicators of human cardiac function. This study started with the aim to investigate the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function.\n\nMethods and resultsGenome wide data from different studies were obtained from public repositories. After quality control and imputation, association analyses confirm the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimers disease (AD). We further explored this unexpected observation which was confirmed by genetic correlation analyses.\n\nConclusionsOur findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimers disease.

genetics↗

bioRxiv2017

Discovery and characterization of coding and non-coding driver mutations in more than 2,500 whole cancer genomes

Discovery of cancer drivers has traditionally focused on the identification of protein-coding genes. Here we present a comprehensive analysis of putative cancer driver mutations in both protein-coding and non-coding genomic regions across >2,500 whole cancer genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We developed a statistically rigorous strategy for combining significance levels from multiple driver discovery methods and demonstrate that the integrated results overcome limitations of individual methods. We combined this strategy with careful filtering and applied it to protein-coding genes, promoters, untranslated regions (UTRs), distal enhancers and non-coding RNAs. These analyses redefine the landscape of non-coding driver mutations in cancer genomes, confirming a few previously reported elements and raising doubts about others, while identifying novel candidate elements across 27 cancer types. Novel recurrent events were found in the promoters or 5UTRs of TP53, RFTN1, RNF34, and MTG2, in the 3UTRs of NFKBIZ and TOB1, and in the non-coding RNA RMRP. We provide evidence that the previously reported non-coding RNAs NEAT1 and MALAT1 may be subject to a localized mutational process. Perhaps the most striking finding is the relative paucity of point mutations driving cancer in non-coding genes and regulatory elements. Though we have limited power to discover infrequent non-coding drivers in individual cohorts, combined analysis of promoters of known cancer genes show little excess of mutations beyond TERT.

genomics↗

bioRxiv2017

A pan-cancer landscape of interactions between solid tumors and infiltrating immune cell populations

Throughout their development, tumors are challenged by the immune system and acquire features to evade its surveillance. A systematic view of these traits is still lacking. Here, we identify genomic and transcriptomic traits associated to the immune-phenotype of 9,403 tumors of 29 solid cancers. In highly cytotoxic immune-phenotypes we found tumors with low clonal heterogeneity enriched by alterations of genes involved in epigenetic regulation, ubiquitin mediated proteolysis, antigen-presentation and cell-cell communication, which may drive resistance. Tumors with immune-phenotypes with mid cytotoxicity present an over-activation of processes involved in invasion and remodeling of neighboring tissues that may foster the recruitment of immune-suppressive cells. Tumors with poor cytotoxic immune-phenotype tend to be of more advanced stages and present frequent alterations in cell cycle, hedgehog, beta-catenin and TGF-beta pathways, which may drive the immune depletion. These results may be exploited to develop novel combinatorial targeting strategies involving immunotherapies.

bioinformatics↗

bioRxiv2017

Cancer Genome Interpreter Annotates The Biological And Clinical Relevance Of Tumor Alterations

While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Most of the alterations observed in tumors, including those in well-known cancer genes, are of uncertain significance. Moreover, the information on tumor genomic alterations shaping the response to existing therapies is fragmented across the literature and several specialized resources. Here we present the Cancer Genome Interpreter (http://www.cancergenomeinterpreter.org), an open access tool that we have implemented to annotate genomic alterations and interpret their possible role in tumorigenesis and in the response to anti-cancer therapies.

cancer biology↗