Highlights

Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of  the most outstanding publications of the year is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy

  • Pan-Cancer analysis of thousands of tumor genomes to identify cancer drivers (2013)

    López-Bigas, Núria (UPF)

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    Pan-Cancer analysis of thousands of tumor genomes to identify cancer drivers

    Identifying the complete list of genes involved in cancer development has been a major objective of cancer researchers for more than 30 years, as this is a first step towards the development of therapies that effectively and selectively target cancer genes to specifically kill tumour cells. In recent years systematic approaches to the quest for cancer genes have been undertaken. These involve sampling cancer genomes and sequencing most coding exons or the whole genome. Thousands tumour genomes are being sequenced in the world. Most have been generated as part of large projects and consortia, such as the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). When a tumour genome is sequenced, hundreds or even thousands of somatic mutations are detected; therefore, identifying which of those are involved in driving the tumourigenic process is a major challenge. With hundreds of available sequenced tumour genomes of each cancer type, this problem can be approached by identifying signals of positive selection in the pattern of mutations observed per gene across tumours. We have developed a computational approach to detect driver genes by combining multiple signals of positive selection and have applied it to 3,205 tumors from 12 different cancer types from the TCGA Pan-Cancer project (Weinstein et al., Nature Genetics 2013). We have identified 291 high confident cancer driver genes. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumour type. The novel driver candidates complement our current picture of the emergence of these diseases (Tamborero et al., Scientific Reports 2013). In addition we have described IntOGen-mutations, a novel web platform for cancer genomes interpretation, which analyses not only TCGA pan-cancer data but also additional datasets generated by other initiatives such as those included within the ICGC. The resource allows users to identify driver mutations, genes and pathways acting on thousands of tumours from different cancer sites and to analyze newly sequenced tumor genomes and identify relevant mutations by putting them in the context of the accumulated knowledge (Gonzalez-Perez et al., Nature Methods 2013).

  • A new monograph on concentration inequalities (2013)

    Lugosi, Gábor (UPF)

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    A new monograph on concentration inequalities

    Oxford University Press published a new monograph onconcentration inequalities, written by Gábor Lugosi and his co-authors, Stéphane Boucheron and Pascal Massart.Concentration inequalities for functions of independent random variables is an area of probability theory that has witnessed a great revolution in the last few decades, and has applications in a wide variety of areas such as machine learning, statistics, discrete mathematics, and high-dimensional geometry. Roughly speaking, if a function of many independent random variables does not depend too much on any of the variables then it is concentrated in the sense that with high probability, it is close to its expected value. This book offers a host of inequalities to illustrate this rich theory in an accessible way by covering the key developments and applications in the field.The authors describe the interplay between the probabilistic structure (independence) and a variety of tools ranging from functional inequalities to transportation arguments to information theory. Applications to the study of empirical processes, random projections, random matrix theory, and threshold phenomena are also presented.A self-contained introduction to concentration inequalities, it includes a survey of concentration of sums of independent random variables, variance bounds, the entropy method, and the transportation method. Deep connections with isoperimetric problems are revealed whilst special attention is paid to applications to the supremum of empirical processes.

  • Great ape genetic diversity and population history (2013)

    Marquès Bonet, Tomàs (UPF)

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    Great ape genetic diversity and population history

    A new study has, for the first time, sequenced the genomes of a large number of Great apes from across Africa and South-East Asia. The work focused on characterizing as much wild genetic diversity as possible from the worlds rapidly dwindling great ape populations. Great apes are a group of species made up of humans and our closest relatives, chimpanzees, gorillas and orangutans. These species all share a common ancestor about 14-16 million years ago, but chimpanzees, for example diverged from humans much more recently, ~6 million years ago. The study provides one of the most detailed and comprehensive analyses of genetic diversity of wild-born great apes to date—species which are now all considered endangered.                    The researchers found that human genomes show relatively little variation between each other in comparison to most great apes. Few ape species are as shallow as human when it comes to genetic diversity.   The genomes of a pair of orangutans, for example differ at more than 2 out of every 1000 base-pairs, compared to 1 out of every 1000 base-pairs between any two humans.  A few species of great apes, however, were more similar to humans in that they showed a dearth of genetic variation; namely Eastern lowland gorillas, Western chimpanzees and bonobos.  All of these species showed evidence of severe bottlenecks in their ancient history possibly explaining the reduced genetic diversity.            The researchers focused particularly on the comparing the evolutionary history of our closest relatives, chimpanzees, who are dispersed across Africa and classified into four major groups, or, subspecies. An open question among evolutionary biologists has been how these four populations relate to one another. By sequencing multiple individuals from each group, the researchers were able to resolve the phylogenetic relationship among these subspecies distinguishing two genetically distinct groups of chimps. What also became apparent to the researchers was the complexity of the evolutionary history of chimps compared to humans. The patterns of genetic diversity were consistent with extensive gene flow or migration between ancestral populations with sudden expansions in population size followed by crashes.  The basis for these population collapses is unclear but does coincide, in part, with a period of time when human p

  • The search for the dark side of the Universe (2013)

    Martínez Pérez, Mario (IFAE)

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    The search for the dark side of the Universe

    After the discovery of the Higgs boson in 2012, the next mission of the LHC, in addition to carry out a detailed study of the new particle, is to put light on the nature of the dark matter in the cosmos, and to determine whether super-symmetry and/or new extra spatial dimensions are realized in nature. Monojet final states (see Figure 1) have been traditionally studied in these contexts.Astronomical observations of galaxies and galaxy clusters have established the existence of an important non-baryonic dark matter (non-luminous) component in the universe. According to the current understanding of cosmology, the dark matter would contribute about 23% of the total mass-energy budget of the universe. The nature of the dark matter remains unknown.  It is now commonly accepted that the dark matter should be made of weakly interacting massive particles  (WIMPs) acting through gravitational or weak interactions. At the LHC, WIMPs could be produced in pairs leaving the experimental devices undetected.  Such events could be identified by the presence of an energetic jet from initial-state radiation, leading again to a monojet signature.   The LHC experiments have a unique sensitivity for dark matter candidates with masses below 4 GeV and are complementary to other dark matter searches. Models with large extra spatial dimensions aim to provide a solution to the mass hierarchy problem (related to the large difference between the electroweak unification scale ~102 GeV and the Planck scale ~1019 GeV) by postulating the presence of n extra dimensions such that the Planck scale in 4+n dimensions becomes naturally close to the electroweak scale.   In these models, gravitons (the hypothesized particle acting as mediator of the gravitational interaction) are produced in association with a jet of hadrons leading to a monojet signature in the final state.The ATLAS collaboration have searched for new phenomena in monojet final states in the 2011 and 2012 data at 7 TeV  and 8 TeV, respectively [1,2]. The data are  in good agreement with the SM predictions (see Figure 2).   The results have been translated into updated exclusion limits on the presence of large extra spatial dimensions and the production of WIMPs, and new limits on gravitino production (the supersymmetric partner of the graviton) resulting in the best lower bound to date on the gravitino mass.

  • Nanoscale metal-organic frameworks and related hollow superstructures built with fast-spray-drying (2013)

    Maspoch Comamala, Daniel (ICN2)

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    Nanoscale metal-organic frameworks and related hollow superstructures built with fast-spray-drying

    Metal-organic frameworks (MOFs) are among the most attractive porous materials today. Their miniaturization to the nanoscale, to yield nanoMOFs, is expected to expand their scope to myriad applications, from drug-delivery to membranes, open up novel avenues to more traditional storage and catalysis applications, and enable creation of sophisticated superstructures. However, methods for reliable nanoscale MOF synthesis, in which the precise patterning of the structure is intimately linked to its functional capacity, have been limited. We have reported and patented the use of spray drying as a versatile, general methodology to confine the crystallization of nanoMOFs and their assembly into hollow MOF superstructures smaller than 5 μm-in-diameter. This strategy conceptually mimics emulsions used by chemists to confine the synthesis of materials, but does not require secondary immiscible solvents or surfactants. We have demonstrated that this process enables shaping of MOFs into hollow superstructures that can subsequently be processed into stable colloids comprising discrete, homogeneous nanoMOFs. We have also showed that our spray-drying strategy can be applied to entrap guest species within the superstructures, thereby providing new routes to capsules, reactors and composite materials.

  • CPEB1 coordinates alternative 3'UTR formation with translational regulation (2013)

    Méndez de la Iglesia, Raúl (IRB Barcelona)
    Valcárcel Juárez, Juan (CRG)

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    CPEB1 coordinates alternative 3'UTR formation with translational regulation

    More than half of mammalian genes generate multiple mRNA isoforms that differ in their 3’ untranslated regions (3’UTRs) and therefore in regulatory sequences; however, the mechanisms coordinating alternative 3’UTR processing for specific mRNA populations remain poorly defined. Here we report that the Cytoplasmic Polyadenylation Element Binding protein 1 (CPEB1), an RNA-binding protein that regulates mRNA translation, also controls alternative 3’UTR processing. CPEB1 shuttles to the nucleus, where it co-localizes with splicing factors and mediates 3’UTR shortening of hundreds of mRNAs, thereby modulating their translation efficiency in the cytoplasm. CPEB1-mediated 3’UTR shortening correlates with cell proliferation and tumorigenesis. CPEB1 binding to pre-mRNAs not only directs the use of alternative polyadenylation sites, but also changes alternative splicing by preventing U2AF65 recruitment. Our results reveal a novel function of CPEB1 in mediating alternative 3' UTR processing, coupled to regulation of mRNA translation.

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