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 & Gene. The organization has 8093 authors who have published 23570 publications receiving 858431 citations. The organization is also known as: Universitat Pompeu Fabra & UPF.

Assessment of transcript reconstruction methods for RNA-seq

Abstract: We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from RNA-seq data. Our results show that most algorithms are able to identify discrete transcript components with high success rates but that assembly of complete isoform structures poses a major challenge even when all constituent elements are identified. Expression-level estimates also varied widely across methods, even when based on similar transcript models. Consequently, the complexity of higher eukaryotic genomes imposes severe limitations on transcript recall and splice product discrimination that are likely to remain limiting factors for the analysis of current-generation RNA-seq data.

Towards complete and error-free genome assemblies of all vertebrate species

Abstract: High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

Discourse and Context: A Sociocognitive Approach

Abstract: Preface Acknowledgements 1. Towards a theory of context 2. Context and language 3. Context and cognition 4. Context and discourse 5. Conclusions References Subject index Author index.

Ongoing Cortical Activity at Rest: Criticality, Multistability, and Ghost Attractors

Abstract: The ongoing activity of the brain at rest, i.e., under no stimulation and in absence of any task, is astonishingly highly structured into spatiotemporal patterns. These spatiotemporal patterns, called resting state networks, display low-frequency characteristics (<0.1 Hz) observed typically in the BOLD-fMRI signal of human subjects. We aim here to understand the origins of resting state activity through modeling via a global spiking attractor network of the brain. This approach offers a realistic mechanistic model at the level of each single brain area based on spiking neurons and realistic AMPA, NMDA, and GABA synapses. Integrating the biologically realistic diffusion tensor imaging/diffusion spectrum imaging-based neuroanatomical connectivity into the brain model, the resultant emerging resting state functional connectivity of the brain network fits quantitatively best the experimentally observed functional connectivity in humans when the brain network operates at the edge of instability. Under these conditions, the slow fluctuating (<0.1 Hz) resting state networks emerge as structured noise fluctuations around a stable low firing activity equilibrium state in the presence of latent "ghost" multistable attractors. The multistable attractor landscape defines a functionally meaningful dynamic repertoire of the brain network that is inherently present in the neuroanatomical connectivity.

DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Abstract: Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.