Computational prediction of CRISPR-impaired non-coding regulatory regions

Genome-wide CRISPR screens are becoming more widespread and allow the simultaneous interrogation of thousands of genomic regions. Although recent progress has been made in the analysis of CRISPR screens, it is still an open problem how to interpret CRISPR mutations in non-coding regions of the genome. Most of the tools concentrate on the interpretation of mutations introduced in gene coding regions. We introduce a computational pipeline that uses epigenomic information about regulatory elements for the interpretation of CRISPR mutations in non-coding regions. We illustrate our approach on the analysis of a genome-wide CRISPR screen in hTERT-RPE-1 cells and reveal novel regulatory elements that mediate chemoresistance against doxorubicin in these cells. We infer links to established and to novel chemoresistance genes. Our approach is general and can be applied on any cell type and with different CRISPR enzymes

Fluid history during burial and exhumation of an oil paleo-reservoir (mylonitic metavolcanics, Vendée, France)

International audienc

Fluid history during deep burial and exhumation of an oil-bearing volcanics: Hercynian belt of southern Brittany, France

International audienceIn southern Brittany (France), the Porphyroid nappe, a Variscan tectonic unit made of volcanic pyroclastic deposits that was involved in a low-temperature/high-pressure prograde metamorphic path followed by exhumation and extension, displays evidence for very large and distributed strains achieved through dissolution/crystallization processes. Such distributed strains at low temperature are rather unusual in felsic lithologies. Recent studies have documented that these rocks deformed within a system closed to fluids. This paper presents results of detailed analyses of fluid inclusions and stable isotopes within the deformed metavolcanics and their undeformed counterparts in order to document the fluid history of the tectonic unit. Results show that its initial thermal evolution, likely occurring in a context of basin inversion, involved important open-system alteration, with K-metasomatism (adularization), oil impregnation and hydration. During the subsequent tectonic evolution, the fluids maintained a constant composition in the C-H-O-N system within the Porphyroid nappe and its para-autochthon, being water-rich and containing hydrocarbon components likely related to oil pyrolysis/oxidation. Atoll-like fluid inclusion morphology and rare undisturbed fluid inclusions with steep isochore slopes are consistent (> 750 MPa) with pressures estimated for the peak of metamorphism using mineral solid-solution thermodynamics. Fluid inclusions indicate a sub-isothermal retrograde path (between 420 and 300°C) followed by a high thermal gradient at the end of the retrograde path. Within the underlying para-autochthonous unit, only the late, high-temperature gradient is recorded by fluid inclusions. The sub-isothermal low-grade path suggests fast exhumation of the unit, without thermal relaxation. The high geotherm observed at the end of the P-T path is consistent with the post-thickening extensional collapse and associated intrusion of granites documented in the area. Hydration and heterogeneous oil/water distribution achieved in the early metasomatic evolution of the porous pyroclastic deposits are responsible for subsequent fluid confining in the Porphyroid nappe and for its strongly distributed strain pattern

Fluid history during burial and exhumation of an oil paleo-reservoir (mylonitic metavolcanics, Vendée, France)

International audienc

Six points à retenir sur les déterminants de la "juste" portion [expertise pour Nestlé]

Nestlé a initié une réflexion avec un comité d'experts pluridisciplinaires indépendants pour identifier et comprendre les déterminants de la portion, levier essentiel, mais complexe, pour réguler la prise alimentaire.La synthèse de leurs réflexions s’articule en 6 points clés, soutenus par une analyse de la littérature scientifique, qui sont : • Une portion ni normée, ni injonctive• Une portion réaliste• Une portion personnalisée• Une portion associée à l’hédonisme• Une portion qui intègre les aspects sociaux• Une portion déterminée intuitivemen

Six points à retenir sur les déterminants de la "juste" portion [expertise pour Nestlé]

Nestlé a initié une réflexion avec un comité d'experts pluridisciplinaires indépendants pour identifier et comprendre les déterminants de la portion, levier essentiel, mais complexe, pour réguler la prise alimentaire.La synthèse de leurs réflexions s’articule en 6 points clés, soutenus par une analyse de la littérature scientifique, qui sont : • Une portion ni normée, ni injonctive• Une portion réaliste• Une portion personnalisée• Une portion associée à l’hédonisme• Une portion qui intègre les aspects sociaux• Une portion déterminée intuitivemen

Six points à retenir sur les déterminants de la "juste" portion [expertise pour Nestlé]

Nestlé a initié une réflexion avec un comité d'experts pluridisciplinaires indépendants pour identifier et comprendre les déterminants de la portion, levier essentiel, mais complexe, pour réguler la prise alimentaire.La synthèse de leurs réflexions s’articule en 6 points clés, soutenus par une analyse de la littérature scientifique, qui sont : • Une portion ni normée, ni injonctive• Une portion réaliste• Une portion personnalisée• Une portion associée à l’hédonisme• Une portion qui intègre les aspects sociaux• Une portion déterminée intuitivemen

Bioinformatics analysis quantifies neighborhood preferences of cancer cells in Hodgkin lymphoma

Motivation Hodgkin lymphoma is a tumor of the lymphatic system and represents one of the most frequent lymphoma in the Western world. It is characterized by Hodgkin cells and Reed-Sternberg cells, which exhibit a broad morphological spectrum. The cells are visualized by immunohistochemical staining of tissue sections. In pathology, tissue images are mainly manually evaluated, relying on the expertise and experience of pathologists. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of cancer cells is of great interest. Results Here, we systematically quantified and investigated cancer cell properties and their spatial neighborhood relations by applying statistical analyses to whole slide images of Hodgkin lymphoma and lymphadenitis, which describes a non-cancerous inflammation of the lymph node. We differentiated cells by their morphology and studied the spatial neighborhood relation of more than 400,000 immunohistochemically stained cells. We found that, according to their morphological features, the cells exhibited significant preferences for and aversions to cells of specific profiles as nearest neighbor. We quantified differences between Hodgkin lymphoma and lymphadenitis concerning the neighborhood relations of cells and the sizes of cells. The approach can easily be applied to other cancer types

Bioinformatics analysis of whole slide images reveals significant neighborhood preferences of tumor cells in Hodgkin lymphoma

In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significant favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types

Integrative analysis of epigenetics data identifies gene-specific regulatory elements

Understanding the complexity of transcriptional regulation is a major goal of computational biology. Because experimental linkage of regulatory sites to genes is challenging, computational methods considering epigenomics data have been proposed to create tissue-specific regulatory maps. However, we showed that these approaches are not well suited to account for the variations of the regulatory landscape between cell-types. To overcome these drawbacks, we developed a new method called STITCHIT, that identifies and links putative regulatory sites to genes. Within STITCHIT, we consider the chromatin accessibility signal of all samples jointly to identify regions exhibiting a signal variation related to the expression of a distinct gene. STITCHIT outperforms previous approaches in various validation experiments and was used with a genome-wide CRISPR-Cas9 screen to prioritize novel doxorubicin-resistance genes and their associated non-coding regulatory regions. We believe that our work paves the way for a more refined understanding of transcriptional regulation at the gene-level