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OBJECTIVES: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. METHODS: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. RESULTS: Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received before stricture diagnosis included MODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). CONCLUSION: In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.
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Doença de Crohn , Intestino Delgado , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Masculino , Estudos Retrospectivos , Feminino , Fatores de Risco , Criança , Intestino Delgado/cirurgia , Intestino Delgado/patologia , Adolescente , Constrição Patológica/etiologia , França , Imageamento por Ressonância Magnética , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgiaRESUMO
Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease), to provide a comparable reference of normal gene expression. Curation includes very large datasets such as GTEx (re-annotation of samples as 'healthy' or not) as well as many small ones. Data are integrated and made comparable between species thanks to consistent data annotation and processing, and to calls of presence/absence of expression, along with expression scores. As a result, Bgee is capable of detecting the conditions of expression of any single gene, accommodating any data type and species. Bgee provides several tools for analyses, allowing, e.g., automated comparisons of gene expression patterns within and between species, retrieval of the prefered conditions of expression of any gene, or enrichment analyses of conditions with expression of sets of genes. Bgee release 14.1 includes 29 animal species, and is available at https://bgee.org/ and through its Bioconductor R package BgeeDB.
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Curadoria de Dados , Bases de Dados Genéticas , Transcriptoma/genética , Animais , Regulação da Expressão Gênica , Anotação de Sequência Molecular , Interface Usuário-ComputadorRESUMO
INTRODUCTION: The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and Belgian centers. METHODS: All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included. RESULTS: 271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72â% of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90â% (423/470) and diagnostic in cases of neonatal cholestasis in 10â% of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92â% of cases (270/294); pancreatic cannulation in 96â% of cases (169/176); and planned therapeutic procedures in 92â% of cases (388/423). The overall complication rate was 19â% (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12â% of cases (40/340) and sepsis in 5â% (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio [OR] 0.1, 95â% confidence interval [CI] 0.01â-â0.75; Pâ=â0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95â%CI 1.7â-â31.05; Pâ=â0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality. CONCLUSION: Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports.
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Coledocolitíase , Pancreatite , Cateterismo , Criança , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Recém-Nascido , Pancreatite/epidemiologia , Pancreatite/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVES: The use of semielemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product. METHODS: We performed a retrospective multicenter survey on a cohort of patients receiving this semielemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6, and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events. RESULTS: We recruited 136 patients ages 9.8â±â4.4 years at baseline. Mean body mass index z score was -1.0â±â1.8; mean height z score was -1.1â±â1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and hematological (19.9%). The indications for a semielemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%), and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children. CONCLUSIONS: This semielemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet.
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Nutrição Enteral , Alimentos Formulados , Criança , Estudos de Coortes , Estudos Transversais , Feminino , França , Serviços de Assistência Domiciliar , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
MOTIVATION: Most anatomical ontologies are species-specific, whereas a framework for comparative studies is needed. We describe the vertebrate Homologous Organs Groups ontology, vHOG, used to compare expression patterns between species. RESULTS: vHOG is a multispecies anatomical ontology for the vertebrate lineage. It is based on the HOGs used in the Bgee database of gene expression evolution. vHOG version 1.4 includes 1184 terms, follows OBO principles and is based on the Common Anatomy Reference Ontology (CARO). vHOG only describes structures with historical homology relations between model vertebrate species. The mapping to species-specific anatomical ontologies is provided as a separate file, so that no homology hypothesis is stated within the ontology itself. Each mapping has been manually reviewed, and we provide support codes and references when available. AVAILABILITY AND IMPLEMENTATION: vHOG is available from the Bgee download site (http://bgee.unil.ch/), as well as from the OBO Foundry and the NCBO Bioportal websites. CONTACT: bgee@isb-sib.ch; frederic.bastian@unil.ch.
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Bases de Dados Factuais , Terminologia como Assunto , Vertebrados/anatomia & histologia , Animais , Evolução Biológica , Biologia Computacional/métodos , Expressão Gênica , Vertebrados/classificação , Vocabulário ControladoRESUMO
INTRODUCTION: With advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD. METHODS: The Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children's Hospital Feeding Scale. RESULTS: Of the 248 eligible children, 145 children, with a median age of 2.3 years (Q1-Q3 1.8-2.9, min-max 1.1-4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication. CONCLUSION: PFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth.
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Atresia Esofágica/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Anastomose Cirúrgica/métodos , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Nutrição Enteral/métodos , Atresia Esofágica/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , França/epidemiologia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/epidemiologia , PrevalênciaRESUMO
Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Nutrição Parenteral no Domicílio , Adulto , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Criança , Estudos Transversais , Humanos , Nutrição Parenteral no Domicílio/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Epigenetic regulation of gene dosage by genomic imprinting of some autosomal genes facilitates normal reproductive development in both mammals and flowering plants. While many imprinted genes have been identified and intensively studied in mammals, smaller numbers have been characterized in flowering plants, mostly in Arabidopsis thaliana. Identification of additional imprinted loci in flowering plants by genome-wide screening for parent-of-origin specific uniparental expression in seed tissues will facilitate our understanding of the origins and functions of imprinted genes in flowering plants. RESULTS: cDNA-AFLP can detect allele-specific expression that is parent-of-origin dependent for expressed genes in which restriction site polymorphisms exist in the transcripts derived from each allele. Using a genome-wide cDNA-AFLP screen surveying allele-specific expression of 4500 transcript-derived fragments, we report the identification of 52 maternally expressed genes (MEGs) displaying parent-of-origin dependent expression patterns in Arabidopsis siliques containing F1 hybrid seeds (3, 4 and 5 days after pollination). We identified these MEGs by developing a bioinformatics tool (GenFrag) which can directly determine the identities of transcript-derived fragments from (i) their size and (ii) which selective nucleotides were added to the primers used to generate them. Hence, GenFrag facilitates increased throughput for genome-wide cDNA-AFLP fragment analyses. The 52 MEGs we identified were further filtered for high expression levels in the endosperm relative to the seed coat to identify the candidate genes most likely representing novel imprinted genes expressed in the endosperm of Arabidopsis thaliana. Expression in seed tissues of the three top-ranked candidate genes, ATCDC48, PDE120 and MS5-like, was confirmed by Laser-Capture Microdissection and qRT-PCR analysis. Maternal-specific expression of these genes in Arabidopsis thaliana F1 seeds was confirmed via allele-specific transcript analysis across a range of different accessions. Differentially methylated regions were identified adjacent to ATCDC48 and PDE120, which may represent candidate imprinting control regions. Finally, we demonstrate that expression levels of these three genes in vegetative tissues are MET1-dependent, while their uniparental maternal expression in the seed is not dependent on MET1. CONCLUSIONS: Using a cDNA-AFLP transcriptome profiling approach, we have identified three genes, ATCDC48, PDE120 and MS5-like which represent novel maternally expressed imprinted genes in the Arabidopsis thaliana seed. The extent of overlap between our cDNA-AFLP screen for maternally expressed imprinted genes, and other screens for imprinted and endosperm-expressed genes is discussed.
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Arabidopsis/genética , Perfilação da Expressão Gênica/métodos , Genes de Plantas , Impressão Genômica , Sementes/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Biologia Computacional , Metilação de DNA , DNA Complementar/genética , DNA de Plantas/genética , Endosperma/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Microdissecção e Captura a Laser , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SoftwareRESUMO
BACKGROUND: Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of metastatic subtyping during the initial metastatic event in a prospective study. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting the findings transferability to clinical use. METHODS: We developed a multicenter, single-arm, prospective clinical trial in order to address these issues. Between November 2010 and September 2013, 123 eligible patients were included. Patients at the first, untreated metastatic event were eligible. All matched primary tumors and metastatic samples were centrally reviewed for pathological typing. Targeted and whole-exome sequencing was applied to matched pairs of frozen tissue. A multivariate overall survival analysis was performed (median follow-up 64 months). RESULTS: Per central review in 84 patients (out of 130), we show that luminal A breast tumors are more prone to subtype switching. By combining targeted sequencing of a 91 gene panel (n = 67) and whole-exome sequencing (n = 30), a slight excess of mutations is observed in the metastases. Luminal A breast cancer has the most heterogeneous mutational profile and the highest number of mutational signatures, when comparing primary tumor and the matched metastatic tissue. Tumors with a subtype change have more mutations that are private. The metastasis-specific mutation load is significantly higher in late than in de novo metastases. The most frequently mutated genes were TP53 and PIK3CA. The most frequent metastasis-specific druggable genes were PIK3CA, PTEN, KDR, ALK, CDKN2A, NOTCH4, POLE, SETD2, SF3B1, and TSC2. Long-term outcome is driven by a combination of tumor load and metastasis biology. CONCLUSIONS: Profiling of the first, untreated, metastatic event of breast cancer reveals a profound heterogeneity mostly in luminal A tumors and in late metastases. Based on this profiling, we can derive information relevant to prognosis and therapeutic intervention, which support current guidelines recommending a biopsy at the first metastatic relapse. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov ( NCT01956552 ).
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Mutação/genética , Metástase Neoplásica , Filogenia , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Sequenciamento do ExomaRESUMO
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-ß and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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Autoanticorpos/imunologia , COVID-19/imunologia , Interferon Tipo I/imunologia , Pneumonia/imunologia , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Adulto JovemRESUMO
During development vertebrate embryos pass through a stage where their morphology is most conserved between species, the phylotypic period (approximately the pharyngula). To explain the resistance to evolutionary changes of this period, one hypothesis suggests that it is characterized by a high level of interactions. Based on this hypothesis, we examined protein-protein interactions, signal transduction cascades and miRNAs over the course of zebrafish development, and the conservation of expression of these genes in mouse development. We also investigated the characteristics of genes highly expressed before or during the presumed phylotypic period. We show that while there is a high diversity of interactions during the phylotypic period (protein-DNA, RNA-RNA, cell-cell, and between tissues), which is well conserved with mouse, there is no clear difference with later, more morphologically divergent, stages. We propose that the phylotypic period may rather be the expression at the morphological level of strong conservation of molecular processes earlier in development.
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Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento , Transdução de Sinais , Vertebrados/fisiologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Animais , Camundongos , MicroRNAs/fisiologia , Mapeamento de Interação de Proteínas , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
KEY MESSAGE: Reproduction in triploid plants is important for understanding polyploid population dynamics. We show that genetically identical reciprocal F1 hybrid triploids can display transgenerational epigenetic effects on viable F2 seed development. The success or failure of reproductive outcomes from intra-species crosses between plants of different ploidy levels is an important factor in flowering plant evolution and crop breeding. However, the effects of inter-ploidy cross directions on F1 hybrid offspring fitness are poorly understood. In Arabidopsis thaliana, hybridization between diploid and tetraploid plants can produce viable F1 triploid plants. When selfed, such F1 triploid plants act as aneuploid gamete production "machines" where the vast majority of gametes generated are aneuploid which, following sexual reproduction, can generate aneuploid swarms of F2 progeny (Henry et al. 2009). There is potential for some aneuploids to cause gametophyte abortion and/or F2 seed abortion (Henry et al. 2009). In this study, we analyse the reproductive success of 178 self-fertilized inter-accession F1 hybrid triploids and demonstrate that the proportions of aborted or normally developed F2 seeds from the selfed F1 triploids depend upon a combination of natural variation and cross direction, with strong interaction between these factors. Single-seed ploidy analysis indicates that the embryonic DNA content of phenotypically normal F2 seeds is highly variable and that these DNA content distributions are also affected by genotype and cross direction. Notably, genetically identical reciprocal F1 hybrid triploids display grandparent-of-origin effects on F2 seed set, and hence on the ability to tolerate aneuploidy in F2 seed. There are differences between reciprocal F1 hybrid triploids regarding the proportions of normal and aborted F2 seeds generated, and also for the DNA content averages and distributions of the F2 seeds. To identify genetic variation for tolerance of aneuploidy in F2 seeds, we carried out a GWAS which identified two SNPs, termed MOT and POT, which represent candidate loci for genetic control of the proportion of normal F2 seeds obtained from selfed F1 triploids. Parental and grandparental effects on F2 seeds obtained from selfed F1 triploids can have transgenerational consequences for asymmetric gene flow, emergence of novel genotypes in polyploid populations, and for control of F2 seed set in triploid crops.
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Arabidopsis/genética , Genoma de Planta/genética , Ploidias , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Evolução Biológica , Diploide , Epigenômica , Genótipo , Células Germinativas Vegetais , Hibridização Genética , Magnoliopsida , Fenótipo , Polinização , Reprodução , Autofertilização , TriploidiaRESUMO
BACKGROUND: Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent 'natural' phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes. RESULTS: Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued. CONCLUSIONS: The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. THE ONTOLOGY RELEASE FILES ASSOCIATED WITH THE ONTOLOGY MERGE DESCRIBED IN THIS MANUSCRIPT ARE AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ CURRENT ONTOLOGY RELEASE FILES ARE AVAILABLE ALWAYS AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/
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As part of the development of the database Bgee (a dataBase for Gene Expression Evolution), we annotate and analyse expression data from different types and different sources, notably Affymetrix data from GEO and ArrayExpress, and RNA-Seq data from SRA. During our quality control procedure, we have identified duplicated content in GEO and ArrayExpress, affecting â¼14% of our data: fully or partially duplicated experiments from independent data submissions, Affymetrix chips reused in several experiments, or reused within an experiment. We present here the procedure that we have established to filter such duplicates from Affymetrix data, and our procedure to identify future potential duplicates in RNA-Seq data.