A statistical framework for joint eQTL analysis in multiple tissues

Mapping expression Quantitative Trait Loci (eQTLs) represents a powerful and widely-adopted approach to identifying putative regulatory variants and linking them to specific genes. Up to now eQTL studies have been conducted in a relatively narrow range of tissues or cell types. However, understanding the biology of organismal phenotypes will involve understanding regulation in multiple tissues, and ongoing studies are collecting eQTL data in dozens of cell types. Here we present a statistical framework for powerfully detecting eQTLs in multiple tissues or cell types (or, more generally, multiple subgroups). The framework explicitly models the potential for each eQTL to be active in some tissues and inactive in others. By modeling the sharing of active eQTLs among tissues this framework increases power to detect eQTLs that are present in more than one tissue compared with "tissue-by-tissue" analyses that examine each tissue separately. Conversely, by modeling the inactivity of eQTLs in some tissues, the framework allows the proportion of eQTLs shared across different tissues to be formally estimated as parameters of a model, addressing the difficulties of accounting for incomplete power when comparing overlaps of eQTLs identified by tissue-by-tissue analyses. Applying our framework to re-analyze data from transformed B cells, T cells and fibroblasts we find that it substantially increases power compared with tissue-by-tissue analysis, identifying 63% more genes with eQTLs (at FDR=0.05). Further the results suggest that, in contrast to previous analyses of the same data, the majority of eQTLs detectable in these data are shared among all three tissues.Comment: Summitted to PLoS Genetic

La théorie de la sélection naturelle présentée par Darwin et Wallace

En cette année Darwin (cent cinquantenaire de la parution de L’Origine des espèces, 1859), les écrits présentés ici, datant d’une année auparavant, aident à comprendre la vision en gestation de Darwin. La théorie de la sélection naturelle y est présentée, notamment à partir des fameux « pinsons de Darwin » ; la comparaison avec l’évolution en géologie est esquissée. Bien qu'ayant proposé une théorie solide de l'origine et de la diversité des espèces, Darwin a posé à ses successeurs quantité de nouvelles questions. Comment mesurer les effets de la sélection, notamment comment changent-ils au cours du temps ainsi qu'en fonction de la taille de la population ? Quels sont les liens entre l'impact des variations (les mutations) et leur taux d'occurrence ? Comment la sélection opère-t-elle à chaque niveau d'organisation d'un système dit « complexe » ? Le XXIe siècle arrivant avec son lot d'innovations technologiques permettra sûrement d'aller encore un peu plus loin dans notre compréhension de ces phénomènes, en suivant la voie ouverte autour de Darwin.In the year marking the 150th anniversary of the publication of The Origin of Species (1859), the texts presented here, dating from the previous year, help us to understand Darwin’s burgeoning vision. The theory of natural selection is presented in these texts, notably via the famous “Darwin’s finches”, while the comparison with geological evolution is sketched out. Though he proposed a sound theory for the origin and diversity of species, Darwin left his successors with countless new questions. How can the effects of selection be measured, namely how do they change over time as well as in relation to population size ? What are the links between the impact of variations (mutations) and their occurrence ratio ? How does selection operate at each level of the organisation of a “complex” system ? The 21st century, with its array of technological innovations, will no doubt enable scientists to advance our understanding of these phenomena a little further, following the path opened up around Darwin

New insights towards breeding for mixed cropping of spring pea and barley to increase yield and yield stability

Mixed cropping (MC) is a key strategy to harness agriculture for climate-change. Breeding adapted genotypes can unleash the full potential of MC, both in terms of yield potential and yield stability. To achieve this goal, concepts from both breeding and ecology have to be fused in order to develop a suitable methodology for breeding for MC. In order to advance the field of breeding for MC, we evaluated yield and trait data of pure stands (PS) and mixed stands (MS) of pea (P. sativum L.) and barley (H. vulgare L.) as a legume-cereal model system. Twenty-eight pea and seven barley lines, representing European breeding material, were grown in an incomplete factorial design at two organically managed sites across two years. The general mixing ability (GMA) of pea for total mixture yield was predominant as specific mixing ability (SMA) was absent, facilitating future breeding and seed marketing efforts. The most promising pea cultivar ‘Volt’ resulted in an average total mixture yield increase of 11% (+0.43 t/ha) in MC compared to the average, while the cultivar ’Florida’ led to a yield decrease of − 31% (−1.23 t/ha), highlighting the importance of the choice of the genotype in MS. The analysis of separated MS yields allowed to investigate the underlying mechanistic principles in genotypes’ contribution to MS yields and we revealed the major role of producer (Pr) effects in this context. The correlation between Pr effects and GMA revealed that GMA can be maximized by selecting for high Pr effects. Early vigor, onset of flowering, shoot biomass and stipule length were identified as key traits for indirect selection for high GMA in pea accounting for up to 17% of the identified variation in total mixture yield. PS yields were moderately correlated with mixture yields (r = 0.52, P = 0.013) and can serve as an additional selection criterion. Discrepancies between correlations with PS and MS yields can be exploited to identify unique MS traits that confer niche complementarity in MS. By this method we identified stipule size as such a key trait for increasing GMA of pea. Pea genotype mixtures have a stabilizing effect also in MC systems and exhibited considerably less genotype × year and genotype × location interaction than single genotypes. Our findings close existing knowledge gaps towards breeding for MC and pave the way to develop improved genotypes for diversified cropping systems as a strategy for sustainable intensification and climate change adaptation

Twenty Tips for High-School Students Engaging in Research with Scientists

Ten high-school students from Catalunya and two neuroscientists from the Netherlandsstarted a research collaboration in 2012 investigating how colors may influence learningabilities. This research question was defined and developed solely by the students, withresearchers joining the project later through the guidance of a facilitator and a teacher. Thisrather radical approach to “citizen-science” involved research collaborations on citizen-generatedquestions and was extremely rewarding for both parties involved. It providedskills, empowered participants, and enhanced the social relevance of science while allowinginteractions that might have never happened otherwise. But the process was alsochallenging,which motivated the team of 10 students to propose “Twenty Tips” for otherstudents interested in embarking on a similar journey. In the spirit of all research within thisproject, this article was a collaborative effort between the participants and thus departsstructurally from other scientific articles

The epigenomic landscape of African rainforest hunter-gatherers and farmers

International audienceThe genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation—particularly that correlated with historical lifestyle—shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time

TriAnnot: A Versatile and High Performance Pipeline for the Automated Annotation of Plant Genomes

In support of the international effort to obtain a reference sequence of the bread wheat genome and to provide plant communities dealing with large and complex genomes with a versatile, easy-to-use online automated tool for annotation, we have developed the TriAnnot pipeline. Its modular architecture allows for the annotation and masking of transposable elements, the structural, and functional annotation of protein-coding genes with an evidence-based quality indexing, and the identification of conserved non-coding sequences and molecular markers. The TriAnnot pipeline is parallelized on a 712 CPU computing cluster that can run a 1-Gb sequence annotation in less than 5 days. It is accessible through a web interface for small scale analyses or through a server for large scale annotations. The performance of TriAnnot was evaluated in terms of sensitivity, specificity, and general fitness using curated reference sequence sets from rice and wheat. In less than 8 h, TriAnnot was able to predict more than 83% of the 3,748 CDS from rice chromosome 1 with a fitness of 67.4%. On a set of 12 reference Mb-sized contigs from wheat chromosome 3B, TriAnnot predicted and annotated 93.3% of the genes among which 54% were perfectly identified in accordance with the reference annotation. It also allowed the curation of 12 genes based on new biological evidences, increasing the percentage of perfect gene prediction to 63%. TriAnnot systematically showed a higher fitness than other annotation pipelines that are not improved for wheat. As it is easily adaptable to the annotation of other plant genomes, TriAnnot should become a useful resource for the annotation of large and complex genomes in the future

Evaluer la sélection génomique au sein de croisements bi-parentaux d’espèces pérennes fruitières génotypés par séquençage : point d’étape du projet FruitSelGen

Poste

Considering Transposable Element Diversification in De Novo Annotation Approaches

Transposable elements (TEs) are mobile, repetitive DNA sequences that are almost ubiquitous in prokaryotic and eukaryotic genomes. They have a large impact on genome structure, function and evolution. With the recent development of high-throughput sequencing methods, many genome sequences have become available, making possible comparative studies of TE dynamics at an unprecedented scale. Several methods have been proposed for the de novo identification of TEs in sequenced genomes. Most begin with the detection of genomic repeats, but the subsequent steps for defining TE families differ. High-quality TE annotations are available for the Drosophila melanogaster and Arabidopsis thaliana genome sequences, providing a solid basis for the benchmarking of such methods. We compared the performance of specific algorithms for the clustering of interspersed repeats and found that only a particular combination of algorithms detected TE families with good recovery of the reference sequences. We then applied a new procedure for reconciling the different clustering results and classifying TE sequences. The whole approach was implemented in a pipeline using the REPET package. Finally, we show that our combined approach highlights the dynamics of well defined TE families by making it possible to identify structural variations among their copies. This approach makes it possible to annotate TE families and to study their diversification in a single analysis, improving our understanding of TE dynamics at the whole-genome scale and for diverse species

Caring about reproducibility in scientific research

UMR AGAP équipe DAAV Diversité, adaptation et amélioration de la vign

L'annotation des éléments transposables par la compréhension de leur diversification

mention "très honorable avec félicitations"Tout organisme vivant est le produit d'interactions complexes entre son génome et son environnement, interactions caractérisées par des échanges de matière et d'énergie indispensables à la survie de l'organisme et la transmission de son génome. Depuis la découverte dans les années 1910 que le chromosome est le support de l'information génétique, les biologistes étudient les génomes afin de décrypter les mécanismes et processus à l’œuvre dans le développement des organismes et l'évolution des populations. Grâce aux améliorations technologiques des dernières décennies, plusieurs génomes ont été entièrement séquencés, leur nombre s'accroissant rapidement, mais ils sont loin d'être décryptés pour autant. En effet, certains de leurs composants, les éléments transposables, sont encore mal compris, bien qu'ils aient été détectés chez quasiment toutes les espèces étudiées, et qu'ils puissent représenter jusqu'à 90% du contenu total de leurs génomes. Les éléments transposables sont des fragments du génome possédant la particularité d'être mobiles. Ils ont donc un impact majeur sur la structure des génomes mais également sur l'expression des gènes avoisinants, notamment via des mécanismes épigénétiques. Leur évolution est aussi particulière étant donné qu'ils ont une transmission verticale non-mendélienne et que de nombreux cas de transferts horizontaux ont été mis en évidence. Mais, à part dans le cas de certains organismes modèles pour lesquels nous disposons de séquences de référence, l'annotation des éléments transposables représente souvent un goulot d'étranglement dans l'analyse des séquences génomiques. A cela s'ajoute le fait que les études de génomique comparée montrent que les génomes sont bien plus dynamiques qu'on ne le croyait, en particulier ceux des plantes, ce qui complique d'autant l'annotation précise des éléments transposables. Pendant mes travaux de thèse, j'ai commencé par comparer les programmes informatiques existants utilisés dans les approches d'annotation de novo des éléments transposables. Pour cela, j'ai mis au point un protocole de test sur les génomes de Drosophila melanogaster et Arabidopsis thaliana. Ceci m'a permis de proposer une approche de novo combinant plusieurs outils, capable ainsi de reconstruire automatiquement un grand nombre de séquences de référence. De plus, j'ai pu montrer que notre approche mettait en évidence les variations structurales au sein de familles bien connues, notamment en distinguant des variants structuraux appartenant à une même famille d'éléments transposables, reflétant ainsi la diversification de ces familles au cours de leur évolution. Cette approche a été implémentée dans une suite d'outils (REPET) rendant possible l'analyse des éléments transposables de nombreux génomes de plantes, insectes, champignons et autres. Ces travaux ont abouti à une feuille de route décrivant de manière pratique comment annoter le contenu en éléments transposables de tout génome nouvellement séquencé. Par conséquent, de nombreuses questions concernant l'impact de ces éléments sur l'évolution de la structure des génomes peuvent maintenant être abordées chez différents génomes plus ou moins proches. Je propose également plusieurs pistes de recherche, notamment la simulation des données nécessaires à l'amélioration des algorithmes de détection, démarche complémentaire de la modélisation de la dynamique des éléments transposables