Ouverture des données de la recherche. Guide d'analyse du cadre juridique en France

Avec le soutien du Comité pour la science ouverte (Ministère de l’Enseignement supérieur, de la Recherche et de l’Innovation)The guide on the opening of research data (or Open Data) is intended to support the employees of educational institutions and research organisations in adopting a reasonable approach to opening research data. It is the result of the study of an inter-organisation working group led by the National Institute for Agricultural Research (INRA). It is not an exhaustive guide and is intended to for information purposes alone. It attempts to answer the most common questions such employees may be faced with such as whether it is a voluntary approach or is imposed by regulations and whether it corresponds with their institution's own objectives. The legal framework is cited if it exists. However, the readers are made aware that the legal landscape on this subject is continually shifting and that they need to refer their institution's Open Data policy.Le guide sur l’ouverture des données de recherche (ou Open Data) a pour vocation d’accompagner les agents des établissements concernés (établissements d’enseignement et organismes de recherche) dans une démarche d’ouverture raisonnée des données de recherche. Il est issu des réflexions d’un groupe de travail inter-organismes animé par l’INRA. Il ne prétend pas à l’exhaustivité ; il est fourni uniquement à titre d’information. Il tente de répondre aux questions les plus courantes auxquelles ils pourront être confrontés que cette démarche soit volontaire et réponde aux objectifs de l’établissement ou qu’elle soit imposée par la réglementation. Le cadre légal est cité, lorsqu’il existe. L’attention du lecteur est toutefois attirée sur le paysage très mouvant du droit sur ce sujet et sur la nécessité de se référer à la politique de son établissement en matière d’Open Data

Recommandations sur l'analyse automatique de documents : acquisition, gestion, exploration

The recommendations concern written documents under copyright regardless of their genre and nature. Their aim is to inform public research actors about good practices in text mining in the context of the French 'Digital Republic' Law dated October 7th 2016 and the European directive on copyright in the digital single market dated March 26th 2019. These cover the acquisition and sharing of documents, the use of management, exploration or analysis software, the use of results and the dissemination of document extracts.Les recommandations concernent les documents protégés par un droit d’auteur, c’est-à-dire les documents écrits, quels que soient leurs genres et leur nature. Elles sont destinées à renseigner les acteurs de la recherche publique sur les bonnes pratiques en matière de fouille de texte, à la suite de l’adoption de la loi française « Pour une République Numérique » du 7 octobre 2016 et de la directive européenne sur le droit d’auteur dans le marché unique numérique du 26 mars 2019. Elles portent sur l’acquisition et le partage des documents, l’utilisation de logiciels de gestion, d’exploration ou d’analyse, l’exploitation des résultats et la diffusion d’extraits de documents

Telomere length is key to hepatocellular carcinoma diversity and telomerase addiction is an actionable therapeutic target

International audienceBackground & Aims: Telomerase activation is the earliest event in hepatocellular carcinoma (HCC) development. Thus, we aimed to elucidate the role of telomere length maintenance during liver carcinogenesis.Methods: Telomere length was measured in the tumor and non-tumor liver tissues of 1,502 patients (978 with HCC) and integrated with TERT alterations and expression, as well as clinical and molecular (analyzed by genome, exome, targeted and/or RNA-sequencing) features of HCC. The preclinical efficacy of anti-TERT antisense oligonucleotides (ASO) was assessed in vitro in 26 cell lines and in vivo in a xenograft mouse model.Results: Aging, liver fibrosis, male sex and excessive alcohol consumption were independent determinants of liver telomere attrition. HCC that developed in livers with long telomeres frequently had wild-type TERT with progenitor features and BAP1 mutations. In contrast, HCC that developed on livers with short telomeres were enriched in the non-proliferative HCC class and frequently had somatic TERT promoter mutations. In HCCs, telomere length is stabilized in a narrow biological range around 5.7 kb, similar to non-tumor livers, by various mechanisms that activate TERT expression. Long telomeres are characteristic of very aggressive HCCs, associated with the G3 transcriptomic subclass, TP53 alterations and poor prognosis. In HCC cell lines, TERT silencing with ASO was efficient in highly proliferative and poorly differentiated cells. Treatment for 3 to 16 weeks induced cell proliferation arrest in 12 cell lines through telomere shortening, DNA damage and activation of apoptosis. The therapeutic effect was also obtained in a xenograft mouse model.Conclusions: Telomere maintenance in HCC carcinogenesis is diverse, and is associated with tumor progression and aggressiveness. The efficacy of anti-TERT ASO treatment in cell lines revealed the oncogenic addiction to TERT in HCC, providing a preclinical rationale for anti-TERT ASO treatment in HCC clinical trials.Lay summary: Telomeres are repeated DNA sequences that protect chromosomes and naturally shorten in most adult cells because of the inactivation of the TERT gene, coding for the telomerase enzyme. Here we show that telomere attrition in the liver, modulated by aging, sex, fibrosis and alcohol, associates with specific clinical and molecular features of hepatocellular carcinoma, the most frequent primary liver cancer. We also show that liver cancer is dependent on TERT reactivation and telomere maintenance, which could be targeted through a novel therapeutic approach called antisense oligonucleotides

Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation

International audienceBACKGROUND & AIMS: Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.METHODS: We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.RESULTS: Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.CONCLUSIONS: Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p