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Seminars, events & talks

Thursday, 27th February, 2014, 11:00

Evolutionary Genomics

Are long non-coding RNAs translated?: Ribosome profiling reveals the complexity of eukaryotic proteomes

We have compiled raw sequencing data from ribosome profiling experiments performed in different species (human, mouse, zebrafish, fruit fly, yeast) and used them to assemble transcripts, quantify transcript-ribosome associations, and investigate the coding potential and strength of purifying selection of the putatively translated open reading frames in some long non-coding RNAs. We detected extensive association of lincRNAs with ribosomes, not only observed in mammals but also in the other eukaryotic groups. Surprisingly, some of the lncRNAs show significant sequence similarity to proteins only annotated in Genbank, whereas others show not such similarity but still contain putative short open reading frames. The coding potential of ribosome-associated lncRNAs ORFs, measured using different codon frequency based sequence statistics, is intermediate between intronic ORFs and experimentally validated ORFs. These ORFs are subject to weaker selective constraints than most experimentally validated proteins as inferred from single nucleotide polymorphism densities. Our results suggest that many lncRNAs have coding properties and that this class of genes most likely includes protein-coding genes that are no longer functional as well as genes encoding new, poorly-conserved, peptides.

Speaker: Jorge Ruiz Orera - Evolutionary Genomics, GRIB (IMIM - UPF)

Room Aula-4th floor

Monday, 17th February, 2014, 11:00

Computational Biophysics

Rethinking Binding and Binding Kinetics

Speaker: Jose Duca, Head of Computer-Aided Drug Discovery at Novartis

Room Marie Curie Room

Thursday, 13th February, 2014, 11:00

Computational RNA Biology

Alternative splicing patterns in the Cancer Genome Atlas datasets

Speaker: Endre Sebestyén - Computational Genomics, GRIB (IMIM-UPF)

Room Sala 473.10

Wednesday, 22th January, 2014, 12:00

Integrative Biomedical Informatics

Integrative strategies for biomedical knowledge.

The progress in biomedical research is increasingly hampered by the difficulty of managing and jointly exploiting the huge amount of information that is accumulated and that it is often fragmented into silos. Consequently, the biomedical knowledge discovery can deeply benefit from scientific, technological and organisational advances in the ways that biomedical information is integrated and jointly analysed. Examples of efforts that we are doing in this direction are: 1) the IMI eTOX project, which tries to advance in the in silico prediction of the potential in vivo toxicity of drug candidates by means of information sharing among the pharmaceutical companies and the application of multi-level modelling strategies; 2) DisGeNET, which is a gene-disease database created by integration of gene-disease associations from several resources; 3) the EU-ADR project, which has developed innovative pharmacovigilance strategies by means of joint exploitation of millions of European healthcare records followed by bioinformatics substantiation of the drug-event signals detected; and 4) the recently started IMI EMIF project, which aims to develop a common information framework of patient-level data that will link up and facilitate access to diverse medical and research data sources, opening up new avenues for research.

Speaker: Ferran Sanz, professor of Biostatistics and Biomedical Informatics at Pompeu Fabra University (UPF) and Director of the IMIM-UPF Research Programme on Biomedical Informatics (GRIB).

Room PRBB Auditorium

Thursday, 9th January, 2014, 11:00

GPCR drug discovery

“Analyzing the exome of 7000 tumors to identify cancer drivers and their therapeutical opportunities”

Speaker: Carlota Rubio - Biomedical Genomics, GRIB

Room Aula (473.10)

Monday, 9th December, 2013

Integrative Biomedical Informatics

DisGeNET RDF and its implementation in Open PHACTS

SWAT4LS 2013 – International Semantic Web Applications and Tools for Life Sciences Workshop in Edinburgh (UK)

Speaker: Nuria Queralt - Integrative Biomedical Informatics group (GRIB)

Thursday, 28th November, 2013, 11:00

Computational RNA Biology

"Alteration of alternative splicing and RNA binding proteins across multiple tumors"

Current cancer genomics projects apply high-throughput technologies to discover recurrent genetic variations in patient samples. These efforts are crucial to describe the genetic diversity of cancer and to classify into novel subtypes for improved prognosis and therapeutics. These genome-scale studies focus mostly on the detection of alterations of the DNA and the expression of genes. However, alterations in Alternative Splicing (AS), which hold important signatures that can provide novel prognostic and therapeutical strategies, have not been yet thoroughly characterized. We have used RNA sequencing data from The Cancer Genome Atlas (TCGA) project for hundreds of tumor samples and paired normal tissues to study the splicing changes and differential expression of Splicing Factors (SFs) and RNA binding proteins (RBPs) in 13 different cancer types. We find new proteins and splicing events that are recurrently altered in tumors. Additionally, by using correlations, we detect possible association of RBPs and events, suggesting splicing regulatory modules. Our analysis indicates that different cancers present similar alterations, suggesting a general path for cells towards cancer by concurrent splicing alterations. This analysis provides useful information to elucidate the impact of alternative splicing in the functional dynamics of cell transformation in multiple cancer types and may help uncovering novel therapeutic strategies.

Speaker: Eduardo Eyras - Computacional Genomics group of GRIB (IMIM - UPF)

Room Aula (473.10)

Thursday, 24th October, 2013, 11:00

GPCR drug discovery

“Identification of cancer drivers across tumor types”

Thousands of tumor genomes/exomes are being sequenced as part of the International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas (TCGA) and other initiatives. This opens the possibility to have, for the first time, a comprehensive picture of mutations, genes and pathways involved in the cancer phenotype across tumor types.

We have developed computational methods able to identify signals of positive selection in the pattern of tumor somatic mutations, which point to genes and pathways directly involved in the development of the tumors.

We have applied these approaches to 3025 tumors from 12 different cancer types of the TCGA Pan-Cancer project, identifying 291 high-confidence cancer driver genes acting on those tumors (Tamborero et al 2013).

We have also developed IntOGen-mutations (http://www.intogen.org/mutations), a novel web platform for cancer genomes interpretations, which analyses not only TCGA pan-cancer data but all mutation data from ICGC and other initiatives. The resource allows users to identify driver mutations, genes and pathways acting on more than 6000 tumors originated in 17 different cancer sites and to analyze newly sequence tumor genomes.

Among the novel cancer drivers identified there are chromatin regulatory factors and splicing factors, which are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment.

In my talk I will summarize all these recent findings.

References:

Tamborero et al., Comprehensive identification of mutations cancer driver genes across 12 tumor types. Scientific Reports 2013. 3:2650 doi:10.1038/srep02650

Gonzalez-Perez et al., IntOGen-mutations identifies cancer drivers across tumor types. Nature Methods 2013 doi:10.1038/nmeth.2642

Gonzalez-Perez et al., The mutational landscape of chromatin regulatory factors across 4623 tumor types. Genome Biology 2013 4(9):r106

Speaker: Núria López-Bigas, Biomedical Genomics, GRIB

Room Ramon y Cajal Room

Thursday, 26th September, 2013, 11:00

Evolutionary Genomics

Gut microbiotas in evolutionary studies: insights from cichlid fishes

With the advent of HT sequencing technologies we have just begun unveiling the genetic and functional diversity of gut microbial consortia, as well as their role in animal evolution. How does the gut microbiota evolve along the host lineages? Can the microbiota be considered as an inherited trait? And if so, is the microbiota a simple mirror or also a driver of the host evolution?

Both diet and host phylogeny are shown as crucial predictors of microbiota features, while the relative contribution of these two factors in recapitulating microbial communities relationships is currently under debate. Therefore closely related species that show a large differentiation of feeding habits represent an especially interesting system to investigate microbiota dynamics in response to concurrent host legacy constraints and selective pressures for rapid adaptation to different diet.

We are currently exploring specificity and dynamics of the gut microbiota in East African Cichlid fishes, which represent a large group of closely related species that underwent a spectacular dietary niche radiation. We recently profiled the gut microbiota of a young tribe of cichlids from lake Tanganyika that transitioned from a generalist feeding to a highly specialized diet primarily based on scales. How did the gut microbiota respond to such diet transition?

Speaker: Laura Baldo - Evolutionary Genomics. Biomedical Informatics, GRIB (IMIM - UPF)

Room Aula (473.10)

Wednesday, 18th September, 2013, 16:30

Integrative Biomedical Informatics

Unfolding diversity: Modeling promiscuity and toxicity in the metabolic space and beyond.

The development of in silico whole-cell model organisms is helping to build the interface between high-throughput biological data and predictive biology. I will present the work of our group based on metabolic circuits to design and optimize biological devices for production, sensing and regulation [1], introducing proof-of-concept applications of such devices for smart therapeutics and synthetic biology. Our approach is formally described through graph balance analysis, providing a methodology that can be used to study diverse coupling mechanisms such as promiscuous interactions [2] or toxicity pathways [3]. The integration of pathway information with whole-cell models might ultimately unveil unexpected synergistic effects originated from system perturbations.

[1] Carbonell P., Planson A.G., Fichera D., Faulon J.L. A retrosynthetic biology approach to metabolic pathway design for therapeutic production. BMC Systems Biology, 5:122, 2011.

[2] Carbonell P., Faulon J.L., Molecular signatures-based prediction of enzyme promiscuity. Bioinformatics, 26(16):2012-2019, 2010.

[3] Planson A.G., Carbonell P., Paillard E., Pollet N., Faulon J.L. Compound toxicity screening and structure-activity relationship modeling in Escherichia coli. Biotechnology and Bioengineering, 109:846-850, 2012.

Speaker: Pablo Carbonell, Institute of Systems and Synthetic Biology (iSSB), Univ. Evry, CNRS, Evry, France.

Room Charles Darwin (PRBB)



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