Pompeu Fabra University

About: Pompeu Fabra University is a education organization based out in Barcelona, Spain. It is known for research contribution in the topics: Population & Context (language use). The organization has 8093 authors who have published 23570 publications receiving 858431 citations. The organization is also known as: Universitat Pompeu Fabra & UPF.

Amphioxus functional genomics and the origins of vertebrate gene regulation

Abstract: Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that-in vertebrates-over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.

A Pan-cancer Landscape of Interactions between Solid Tumors and Infiltrating Immune Cell Populations

Abstract: Purpose: Throughout their development, tumors are challenged by the immune system, and they acquire features to evade its surveillance A systematic view of these traits, which shed light on how tumors respond to immunotherapies, is still lackingExperimental Design: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers We then clustered tumors with similar infiltration pattern to define immunophenotypes Finally, we identified genomic and transcriptomic traits associated to these immunophenotypes across cancer typesResults: In highly cytotoxic immunophenotypes, we found tumors with low clonal heterogeneity enriched for alterations of genes involved in epigenetic regulation, ubiquitin-mediated proteolysis, antigen presentation, and cell-cell communication, which may drive resistance in combination with the ectopic expression of negative immune checkpoints Tumors with immunophenotypes of intermediate cytotoxicity are characterized by an upregulation of processes involved in neighboring tissue invasion and remodeling that may foster the recruitment of immunosuppressive cells Tumors with poorly cytotoxic immunophenotype tend to be of more advanced stages and bear a greater burden of copy number alterations and frequent alterations of cell cycle, hedgehog, β-catenin, and TGFβ pathways, which may cause immune depletionConclusions: We provide a comprehensive landscape of the characteristics of solid tumors that may influence (or be influenced by) the characteristics of their immune infiltrate These results may help interpret the response of solid tumors to immunotherapies and guide the development of novel drug combination strategies Clin Cancer Res; 24(15); 3717-28 ©2018 AACR

High trans-ethnic replicability of GWAS results implies common causal variants.

Abstract: Genome-wide association studies (GWAS) have detected many disease associations. However, the reported variants tend to explain small fractions of risk, and there are doubts about issues such as the portability of findings over different ethnic groups or the relative roles of rare versus common variants in the genetic architecture of complex disease. Studying the degree of sharing of disease-associated variants across populations can help in solving these issues. We present a comprehensive survey of GWAS replicability across 28 diseases. Most loci and SNPs discovered in Europeans for these conditions have been extensively replicated using peoples of European and East Asian ancestry, while the replication with individuals of African ancestry is much less common. We found a strong and significant correlation of Odds Ratios across Europeans and East Asians, indicating that underlying causal variants are common and shared between the two ancestries. Moreover, SNPs that failed to replicate in East Asians map into genomic regions where Linkage Disequilibrium patterns differ significantly between populations. Finally, we observed that GWAS with larger sample sizes have detected variants with weaker effects rather than with lower frequencies. Our results indicate that most GWAS results are due to common variants. In addition, the sharing of disease alleles and the high correlation in their effect sizes suggest that most of the underlying causal variants are shared between Europeans and East Asians and that they tend to map close to the associated marker SNPs.

Origins and Divergence of the Roma (Gypsies)

Abstract: The identification of a growing number of novel Mendelian disorders and private mutations in the Roma (Gypsies) points to their unique genetic heritage. Linguistic evidence suggests that they are of diverse Indian origins. Their social structure within Europe resembles that of the jatis of India, where the endogamous group, often defined by profession, is the primary unit. Genetic studies have reported dramatic differences in the frequencies of mutations and neutral polymorphisms in different Romani populations. However, these studies have not resolved ambiguities regarding the origins and relatedness of Romani populations. In this study, we examine the genetic structure of 14 well-defined Romani populations. Y-chromosome and mtDNA markers of different mutability were analyzed in a total of 275 individuals. Asian Y-chromosome haplogroup VI-68, defined by a mutation at the M82 locus, was present in all 14 populations and accounted for 44.8% of Romani Y chromosomes. Asian mtDNA-haplogroup M was also identified in all Romani populations and accounted for 26.5% of female lineages in the sample. Limited diversity within these two haplogroups, measured by the variation at eight short-tandem-repeat loci for the Y chromosome, and sequencing of the HVS1 for the mtDNA are consistent with a small group of founders splitting from a single ethnic population in the Indian subcontinent. Principal-components analysis and analysis of molecular variance indicate that genetic structure in extant endogamous Romani populations has been shaped by genetic drift and differential admixture and correlates with the migrational history of the Roma in Europe. By contrast, social organization and professional group divisions appear to be the product of a more recent restitution of the caste system of India.

Moment inequalities for functions of independent random variables

Abstract: A general method for obtaining moment inequalities for functions of independent random variables is presented It is a generalization of the entropy method which has been used to derive concentration inequalities for such functions [Boucheron, Lugosi and Massart Ann Probab 31 (2003) 1583-1614], and is based on a generalized tensorization inequality due to Latala and Oleszkiewicz [Lecture Notes in Math, 1745 (2000) 147-168] The new inequalities prove to be a versatile tool in a wide range of applications We illustrate the power of the method by showing how it can be used to effortlessly re-derive classical inequalities including Rosenthal and Kahane-Khinchine-type inequalities for sums of independent random variables, moment inequalities for suprema of empirical processes and moment inequalities for Rademacher chaos and U-statistics Some of these corollaries are apparently new In particular, we generalize Talagrand's exponential inequality for Rademacher chaos of order 2 to any order We also discuss applications for other complex functions of independent random variables, such as suprema of Boolean polynomials which include, as special cases, subgraph counting problems in random graphs