Centre Hospitalier Universitaire de Brest, French Institute of Health and Medical Research
Recent publications
Three macrocyclic tacn (1,4,7-triazacyclononane) derivatives containing one, two and three 2-methylpyridine pendant arms no1py , no2py and no3py , compared to the linear diamine tpen (N,N,N’,N’-Tetrakis(2-methylpyridinyl)-ethylenediamine) known for its capacity to induce...
Background Autosomal dominant polycystic kidney disease (ADPKD) is a common, inherited nephropathy often resulting in kidney failure. It is genetically heterogeneous; along with the major genes, PKD1 and PKD2 , at least 8 others have been suggested. ALG8 pathogenic variants have been associated with autosomal dominant polycystic liver disease and implicated in ADPKD, while ALG9 has been suggested as an ADPKD gene, but details of the phenotypes and penetrance are unclear. Methods We screened >3900 families with cystic kidneys and/or livers using global approaches to detect ALG8 or ALG9 pathogenic variants. In addition, population cohorts with sequence data (Genomics England 100kGP (100kGP), UK Biobank (UKBB), and Mayo Clinic Biobank (MCBB)), were screened for ALG8 / ALG9 pathogenic variants. Results Multicenter screening of individuals with polycystic kidney and/or liver disease identified 51 (1.3%) ALG8 (7 multiplex) and 23 (0.6%) ALG9 (5 multiplex) families; frequencies that were ∼10x and ∼24x greater than non-polycystic kidney disease (PKD) controls. Analysis of individuals with PKD phenotypes in 100kGP, UKBB, and MCBB identified 9 ALG8 (0.39%) and 9 ALG9 (0.39%) families, an enriched frequency over controls. Two individuals had PKD1 and ALG8 pathogenic changes. Eighty-nine percent of individuals with ALG8 mutations with imaging in the entire MCBB had kidney cysts (56%, >10 cysts), with greater median kidney and liver cyst numbers than controls. For ALG9, 78% had kidney cysts (27%, >10 cysts). Individuals with ALG8 mutations typically had mild cystic kidneys with limited enlargement. Liver cysts were common (71%) with enlarged livers (>2L) found in 11/62 patients although surgical intervention was rare. The ALG9 kidney phenotype was also of mild cystic kidneys but enlarged livers were rare; for both genes chronic kidney disease or kidney failure were rare. Conclusions ALG8 and ALG9 are defined as cystic kidney/liver genes but with limited penetrance for lower eGFR.
Introduction Fine motor skill (FMS) development during childhood is essential to many learning processes, especially in school. FMS impairment can have a major impact on children’s quality of life. Developing effective and engaging rehabilitation solutions to train FMS that engage children in the abundant practice required for motor learning can be challenging. Virtual reality (VR) is a promising intervention option offering engaging FMS training tasks and environments that align with evidence-based motor learning principles. Other potential advantages of VR for rehabilitation include accessibility for home-based use and adaptability to individual needs. The objective of this scoping review is to map the extent, range and nature of VR applications focused on FMS training in paediatric rehabilitation, including hardware, software and interventional parameters. Methods and analysis We are following methodological guidelines for scoping review conduct and reporting from the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews recommendations. We will search four databases (Pubmed, Web of Science, PsycInfo and Scopus) for articles that meet inclusion criteria defined by the Population, Concept, Context method; specifically studies focused on development or evaluation of immersive or non-immersive VR applications to deliver FMS training in paediatric rehabilitation. Different populations of children with FMS impairments will be included (such as children with cerebral palsy, children with developmental coordination disorder or attention deficit hyperactivity disorder). The first search took place in December 2023, and a second is planned for February 2025. One reviewer will complete title, abstract and full paper screening, with consultation by a second reviewer in case of uncertainty. A data extraction framework will be tested by two reviewers on five randomly selected studies to ensure inter-rater reliability, and one reviewer will complete data extraction. Quantitative and qualitative extraction will follow JBI guideline recommendations. Results will be presented in a descriptive and tabular format, including a narrative summary. Results will enhance understanding of the potential of FMS training in VR and inform subsequent directions for research and clinical practice. Ethics and dissemination Data for this review will be collected from the published literature. Ethical approval is not required. We will present our findings at scientific conferences and submit this review to a peer-reviewed journal for publication.
Issues Dentists can play a key role in screening for psychoactive substances use. This systematic review aimed to identify the knowledge, attitudes and practices of dentists related to screening for use of psychoactive substances and the facilitating factors and barriers. Approach According to Preferred Reporting Items for Systematic reviews and Meta‐Analyses, four databases were searched until July 2024 to identify reports relating to screening for substance use by dentists. Search terms used key words relating to knowledge, attitudes or practices concerning the screening of tobacco, alcohol or any other substance use. Key Findings Twenty reports met the inclusion criteria for this review. In practice, dentists were more likely to identify tobacco use than alcohol or other substance use. Although the screening for tobacco was widely performed by dentists, the proposal of interventions was less frequent. Despite the opinion of many dentists that screening is part of their professional role, particularly tobacco, their knowledge of how to identify and intervene seemed low. Lack of knowledge or training were identified as barriers. Implications Identification of these factors should encourage greater diffusion of recommended tools for screening and development of initial and continuing training for dentists. These factors should convince decision‐makers to help dentists to identify referral solutions, in particular coordinated care pathways, and to consider the acceptability and feasibility of the screening tools available to dentists. Conclusion Tobacco use was more frequently identified than was other substances, screening was always more frequent than interventions, and lack of training proved to be the main barriers to screening. Education and training in the screening of psychoactive substance use is a key factor in encouraging improved practices, particularly on intervention following detection and on substances other than tobacco.
Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments. Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. Our findings thus suggest that circulating autoreactive CD4 T cells in AILD are imprinted by chronic antigen exposure to promote liver inflammation, thereby serving as a potential target for developing biomarkers and therapies for AILD.
Purpose The aim was to establish a functional MRI protocol for analyzing human stereoscopic vision in clinical practice. The feasibility was established in a cohort of 9 healthy subjects to determine the functional cortical areas responsible for virtually relief vision. Methods Nine healthy right-handed subjects underwent orthoptic examination and functional MRI. The activation paradigms used were based on a block sequence with the projection of static and dynamic 2D and 3D test patterns during three experiments. The test patterns were projected through two separate eyepieces to create stereoscopic vision. SPM software was used for post-processing and data analysis. Results Among the three different test patterns used, the second, which corresponded to a static high-relief image of a billiard, appeared to be significant for identifying cortical area activation during stereoscopy. In the group analysis, only areas V3A and V6 showed statistically significant activation. Individual analysis revealed activation of the rostral IPS and V5/MT+. Conclusion More data is needed to determine the precise cortical area of activation for stereoscopy. This study proposes a useful and accessible method for functional MRI analysis of stereoscopy.
To assess efficacy and safety of dapsone in adult immune thrombocytopenia (ITP), a multicenter randomized controlled trial (RCT) and a real-word study cohort were performed. Participants were adults with primary ITP, transient response to corticosteroids ± intravenous immunoglobulin, and a platelet count ≤ 30x109/L (or ≤ 50x109/L with bleeding). Patients in the RCT were randomized in arm A (prednisone x3weeks+dapsone for 12 months) or arm B (prednisone alone). The observational study involved dapsone initiation at 100 mg/d with standard follow-up. The primary endpoint was the response rate (platelet count >30x109/L and ≥2×baseline) at 52 weeks, with the response rate at 24 weeks and adverse events as secondary endpoints. The RCT enrolled 93 patients (54.8% female), median age 48.5 years (46 in arm A, 47 in arm B). In the intention-to-treat analysis, 78.3% of patients in group A discontinued dapsone after a median of 4.6 weeks due to adverse events (66.7%) or lack of efficacy (33.3%). The response rate at week 52 was 21.7% (95% CI:10.9%-36.4%) in group A versus 8.5% (95% CI:2.7%-18.6%) in group B (p=0.17). The observational study, which was conducted after the end of the RCT, included 46 patients (52.2% female), median age 50.7 years. Adverse events occurred in 30.4%, leading to discontinuation of dapsone in 23.9%, and 13.6% (95% CI: 5.2%-27.4%) met the primary efficacy endpoint. Results from both studies showed an unfavorable risk-benefit ratio for the use of dapsone in adult primary ITP and suggest that, whenever available, second-line options should be used. NCT02627417, NCT02877706
The Bay of Brest (BB, NW France) is a semi-enclosed basin of 180 km² subject to macro-tidal dynamics and to the fluvial influences of the rivers Aulne and Elorn, which combined drain watersheds of 2600 km². This coastal environment is subject to natural climate oscillations overlaid on the long-term landscape transformations inherited from the post-glacial sea level rise and increasing anthropogenic forcing since the Neolithic (6.9 ka BP), and especially from the Bronze Age (4.2 ka BP) onwards. The BB therefore appears suitable for the reconstruction of the interactions between climate, environment and human dynamics across the Holocene. In this study, a palynological stack was created based on five cores (including two new cores PALM-KS05 and PALM-KS06 from the Brest harbour), allowing us to discuss vegetation dynamics over the last 7 kyrs. Since the Neolithic period, the forest cover has decreased in favour of open and agro-pastoral landscapes. This trend is not uniform, however: forest cover first declined slowly around 4 ka BP, then strongly decreased at the end of the Iron Age, before experiencing a revival of about five centuries at the end of the Roman period (1.7–1.2 ka BP). Finally, a drastic fall of tree pollen taxa is recorded at the start of the Middle Ages. This study is the first on long-term Holocene trends that allows discussion of both climatic and anthropogenic forcing at an unprecedent average study resolution of 35 years. We also place this local evolution in a wider context to detail interactions between natural and anthropic forcings over the last 7 kyrs BP at a regional-scale and we discuss paleoenvironments and human dynamics thanks to the incorporation of an up-to-date corpus of archaeological data.
Sex estimation is an important part of skeletal analysis and forensic identification. Traditionally pelvic traits are utilized for accurate sex estimation. However, the long bones, especially humerus, have been proved to be as effective for determine the sex of the individual. The aim of this study was to compare the predictive accuracy of seven statistical modelling techniques including classical statistical methods and machine learning algorithms, to assess the sexual dimorphism of humerus on a French sample based on a metric analysis of 26 measurements. A total of 98 humeral bones (divided in two samples) were measured. Seven statistical models were compared: Linear Discriminant Analysis (LDA), Regularized Discriminant Analysis (RDA), Penalized Logistic Regression (PLR), Flexible Discriminant Analysis (FDA), Support Vector Machine (SVM), and Artificial Neural Network (ANN) and Random Forest (RF). With cross validation, classification accuracy was greater than 90% (ranges between 92% and 98%) for all models without variable selection methods. The simplification of the models has improved the accuracy between 98% and 100% and also a reduction of the number of variables to 6 or less. Penalized logistic regression (PLR), Random Forest (RF) and Linear discriminant analysis (LDA) were the best accuracy models. The measurements made at the proximal part of the humerus (WTT, CSD), at distal part (BEW, WT, MAW, THT) and of the entire bone (PLCT) stand out among the various models. The present study suggests that the humerus is an interesting alternative for sex estimation and that non-classical statistical models can provide a new approach.
Background Real‐world data regarding patients with non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes. Methods A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423). The inclusion criteria were: ≥ 18 years old; diagnosis of stage IIIB‐IV NSCLC with EGFR ex20ins between January 1, 2017 and November 30, 2021; received mobocertinib. Data on demographics, clinical parameters, treatment patterns, mobocertinib exposure, real‐world outcomes, and adverse events (AEs) were collected. Results are also reported by Asian/Non‐Asian races. Results Overall, 105 patients were enrolled (median [IQR] age at initial diagnosis: 64.0 years [56, 71]; women: 62.9%). The most common first‐line of therapy (LoT) was chemotherapy; the most common second LoT was EGFR tyrosine kinase inhibitors. Most patients received mobocertinib during LoT two and three (74.3%); the maximum dose was 160 mg/day for 67.6% of the cohort (mean [SD] daily dose: 130.6 mg [36.68]). The median real‐world progression‐free survival (PFS) on mobocertinib was 4.76 months (95% CI: 3.98, 6.21). The overall response rate and disease control rate were 20.0% and 48.6%, respectively (median duration of response: 8.34 months [95% CI: 3.61, 9.49]). The median overall survival (OS) was 26.28 months (95% CI: 20.21, 36.44). Asian patients had numerically superior PFS and OS compared with non‐Asian patients. Regarding safety analysis, 73 patients (69.5%) experienced any AE. The most common AE was diarrhea (any grade) (52 patients; 49.5%). Conclusions These data illustrate the real‐world effectiveness of mobocertinib.
A substantial number of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) undergo a nephrectomy, especially in work-up for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD. A literature review was performed and extended to a meta-analysis when possible. For this purpose, PubMed and EMBASE were searched up to May 2024. Fifty-four publications, describing a total of 2391 procedures, were included. In addition, an exploratory questionnaire was sent to urologists, nephrologists, and transplant-surgeons. These sources were used to develop practice points about indications, complications, mortality, timing, and technique of nephrectomy. In addition, data on renal embolization as a potential alternative to nephrectomy was explored and summarized. To reach consensus, practice points were defined and improved in three Delphi survey rounds by experts of the European Renal Association Working Group Genes & Kidney and the European Association of Urology Section of Transplantation Urology. A total of 23 practice points/statements were developed, all of which reached consensus. Among others, it was deemed that nephrectomy can be performed successfully for various indications and is an intermediate risk procedure with acceptable mortality and minimal impact on kidney graft function when performed before, in the same session or after transplantation. The complication rate seems to increase when the procedure is performed as an emergency. During the work-up for transplantation, patient complaints should be assessed routinely by questionnaires to indicate symptom burden. Deciding on the need for nephrectomy and exploring potential alternatives such as kidney embolization should be a process of shared decision making, preferably after multidisciplinary consultation.
Over the last decades, back‐calculation (BC) techniques for ocean anthropogenic carbon (Cant) estimation have improved and evolved into different methodologies that are not exempt from various assumptions and limitations. No single optimal BC method exists to date for computing Cant; therefore, it is necessary to continue advancing the broad range of approaches. Here, we present a novel method based on the BC fundamentals that combines marine‐carbonate‐system (MCS) data and the Total Matrix Intercomparison (TMI) framework. This MCS‐TMI approach differs from other BC methods by using the TMI to reconstruct deep‐ocean biogeochemical properties and their preformed conditions. It also incorporates a global sea‐air oxygen disequilibrium term, and a dynamic stoichiometric carbon‐to‐oxygen ratio that depends on the water‐mass ideal time. The MCS‐TMI yields a total Cant inventory of 124 ± 7 Pg C (referred to 1995), in good agreement with previous global Cant climatologies. The MCS‐TMI method uncertainty (±5.6 μmol kg⁻¹) is controlled by input‐data errors that, nonetheless, have a minimal impact on the total Cant inventory. In contrast, our total Cant inventory uncertainty is governed by methodological errors, specifically those related to the TMI's boundary conditions. Our study demonstrates the effectiveness of MCS data‐based climatologies in reconstructing a 3D gridded Cant climatology, and the validity of ocean circulation transport operators for obtaining BC preformed conditions.
Purpose Radiomics-based machine learning (ML) models of amino acid positron emission tomography (PET) images have shown efficiency in glioma prediction tasks. However, their clinical impact on physician interpretation remains limited. This study investigated whether an explainable radiomics model modifies nuclear physicians’ assessment of glioma aggressiveness at diagnosis. Methods Patients underwent dynamic 6-[¹⁸F]fluoro-L-DOPA PET acquisition. With a 75%/25% split for training (n = 63) and test sets (n = 22), an ensemble ML model was trained using radiomics features extracted from static/dynamic parametric PET images to classify lesion aggressiveness. Three explainable ML methods—Local Interpretable Model-agnostic Explanations (LIME), Anchor, and SHapley Additive exPlanations (SHAP)—generated patient-specific explanations. Eighteen physicians from eight institutions evaluated the test samples. During the first phase, physicians analyzed the 22 cases exclusively through magnetic resonance and static/dynamic PET images, acquired within a maximum interval of 30 days. In the second phase, the same physicians reevaluated the same cases (n = 22), using all available data, including the radiomics model predictions and explanations. Results Eighty-five patients (54[39–62] years old, 41 women) were selected. In the second phase, physicians demonstrated a significant improvement in diagnostic accuracy compared to the first phase (0.775 [0.750–0.802] vs. 0.717 [0.694–0.737], p = 0.007). The explainable radiomics model augmented physician agreement, with a 22.72% increase in Fleiss’s kappa, and significantly enhanced physician confidence (p < 0.001). Among all physicians, Anchor and SHAP showed efficacy in 75% and 72% of cases, respectively, outperforming LIME (p ≤ 0.001). Conclusions Our results highlight the potential of an explainable radiomics model using amino acid PET scans as a diagnostic support to assist physicians in identifying glioma aggressiveness.
Previous reports have indicated that during the era of combination antiretroviral therapy, the major causes of morbidity and mortality in people living with HIV (PLWH) were not solely linked to HIV‐related opportunistic infections but also to cancers that were difficult to manage due to HIV‐related immunodeficiency. We investigated whether PLWH who underwent autologous hematopoietic stem cell transplantation (ASCT) for lymphomas experienced significant morbidity over the past thirty years following HIV infection. We conducted a retrospective follow‐up study of 49 PLWH over a 10‐year period following ASCT. We collected survival data, examined the occurrence of long‐term events, assessed CD4 + T‐cell immune recovery, and analysed the correlation between immune recovery and the events experienced by these patients. The data confirmed the significant long‐term effectiveness of ASCT, with an overall survival rate of 78% at 10 years post‐ASCT. Opportunistic infections, which occurred soon after ASCT and were associated with lower CD4 + T‐cell counts, were successfully managed. However, lymphoma relapse, secondary malignancies, cardiovascular disease, and bone disease, which developed years after ASCT, were major causes of morbidity and mortality in this population. Our findings highlight the need for the development and validation of specific tests to predict risk and guide effective interventions for metabolic diseases, secondary malignancies, and lymphoma relapses in PLWH treated with ASCT for lymphoma.
Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood. To fill this gap, we apply systems immunology approaches using single-cell high-dimensional techniques to capture the signature of peripheral immune cells and the diversity of metabolic profiles in RDEB adults, sampled outside of any opportunistic infection and active cancer. Our study, demonstrates the particular inflammation and immunity characteristics of RDEB adults, with activated / effector T and dysfunctional natural killer cell signatures, concomitant with an overall pro-inflammatory lipid signature. Artificial intelligence prediction models and principal component analysis stress that RDEB is not solely confined to cutaneous issues but has complex systemic endotypes marked by immune dysregulation and hyperinflammation. By characterising the phenotype-endotype association in RDEB adults, our study lays the groundwork for translational interventions that could by lessening inflammation, alleviate the everlasting suffering of RDEB patients, while awaiting curative genetic therapies.
Celiac disease (CD) affects the small intestine, leading to a progressive disappearance of intestinal villi, and can be found in association with several other autoimmune and inflammatory conditions. The main objective of this study was to determine the prevalence and the clinical significance of anti-transglutaminase and anti-endomysium antibodies in patients diagnosed with early rheumatoid arthritis (RA) and spondyloarthritis (SpA). We measured anti-transglutaminase and anti-endomysium antibodies in biobanked serum samples at inclusion in two French prospective multicenter cohorts of patients with suspected early rheumatoid arthritis (ESPOIR, n = 713) and spondyloarthritis (DESIR, n = 709). Results were compared with the clinical, laboratory, and radiographic findings obtained in patients during a 10-year follow-up period. In the DESIR cohort, anti-transglutaminase antibodies were evidenced at low levels (less than three times the upper limit of normal) in 2/709 (0.42%) patients and anti-endomysium antibodies in 0/709 (0%). In the ESPOIR cohort, anti-transglutaminase antibodies were evidenced in 6/713 (0.84%) patients and anti-endomysium antibodies in 1/713 (0.14%). Only the latter patient was confirmed to have celiac disease. Interestingly, this patient was ultimately diagnosed with Sjögren’s disease, an autoimmune condition known to be associated with an increased risk of celiac disease. The very low identified prevalence of anti-transglutaminase and anti-endomysium antibodies suggests a negligible risk of celiac disease in patients with early-stage RA or SpA, which are among the most common inflammatory rheumatic conditions. Consequently, routine screening for celiac disease via these antibodies in patients presenting with early inflammatory rheumatic conditions should not be performed except in case of clinical suspicion of celiac disease.
Background Aarskog-Scott syndrome (AAS) is a rare condition with multiple congenital anomalies, caused by hemizygote variants in the FGD1 gene. Its description was based mostly on old case reports, in whom a molecular diagnosis was not always available, or on small series. The aim of this study was to better delineate the phenotype and the natural history of AAS and to provide clues for the diagnosis and the management of the patients. Methods Phenotypic characterisation of the largest reported AAS cohort, comprising 111 male patients with proven causative variants in FGD1 , through comprehensive analyses of clinical data including congenital anomalies, growth and neurodevelopment. Review of photographs and radiographs by experts in dysmorphology and skeletal disorders. Results This study refines the phenotypic spectrum of AAS, with the description of new morphological and radiological features, and refines the prevalence of the features. Short stature is less frequent than previously reported and has a prenatal onset in more than half of the patients. The growth has a specific course with a catch-up during the first decade often leading to low-normal stature in adulthood. Whereas intellectual disability is rare, patients with AAS have a high prevalence of specific learning difficulties and attention hyperactivity disorder. In light of this better knowledge of AAS, we provide management recommendations. Conclusion A better knowledge of the natural history and phenotypic spectrum of AAS will be helpful for the clinical diagnosis and for the interpretation of FGD1 variants using a retrophenotyping strategy, which is becoming the most common way of diagnosis nowadays. Recommendations for care will improve the management of the patients.
Background Spatial organization of the genome is fundamental for ensuring accurate gene expression. This process depends on the communication between gene promoters and distal cis -regulatory elements (CREs), which together make up 8% of the human genome and are supported by the chromatin structure. It is estimated that over 90% of disease-associated variants are located in the non-coding region of the genome and may affect CRE. For the cystic fibrosis transmembrane conductance regulator ( CFTR) gene, a complete understanding of tissue-specific CFTR expression and regulation is missing, in particular in the pancreas. Mechanistic insights into tissue-specific expression may provide clarity on the clinical heterogeneity observed in Cystic Fibrosis and CFTR-related disorders. Methods To understand the role of 3D chromatin architecture in establishing tissue-specific expression of the CFTR gene, we mapped chromatin interactions via circular chromosome conformation capture (4C) and epigenomic regulation through H3K27ac and DNase Hypersensitive site I (DHS) in Capan-1 pancreatic cells. Candidate regulatory regions are validated by luciferase reporter assay and CRISPR-knock out. Results We identified active regulatory regions not only around the CFTR gene but also outside the topologically associating domain (TAD). By performing functional assays, we validated our targets and revealed a cooperative effect of the − 44 kb, -35 kb, + 15.6 kb and 37.7 kb regions, which share common predicted transcription factor (TF) motifs. Comparative 3D genomic analysis and functional assays using the Caco-2 intestinal cell line revealed the presence of tissue-specific CREs. Conclusion By studying the chromatin architecture of the CFTR locus in Capan-1 cells, we demonstrated the involvement of multiple CREs upstream and downstream of the CFTR gene. We also extend our analysis to compare intestinal and pancreatic cells and provide information on the tissue-specificity of CRE. These findings highlight the importance of expanding the search for causative variants beyond the gene coding sequence but also by considering the tissue-specific 3D genome.
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395 members
Adrian Tempescul
  • Clinical Hematology
Zarrin Alavi
  • Centre d'Investigation Clinique & Research and Innovation Unit
Christopher Payan
  • Microbiology
Serge Timsit
  • Neurology and stroke unit
Cros Pierrick
  • Service de pédiatrie
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Brest, France