Molecular epidemiology of DFNB1 deafness in France

BACKGROUND: Mutations in the GJB2 gene have been established as a major cause of inherited non syndromic deafness in different populations. A high number of sequence variations have been described in the GJB2 gene and the associated pathogenic effects are not always clearly established. The prevalence of a number of mutations is known to be population specific, and therefore population specific testing should be a prerequisite step when molecular diagnosis is offered. Moreover, population studies are needed to determine the contribution of GJB2 variants to deafness. We present our findings from the molecular diagnostic screening of the GJB2 and GJB6 genes over a three year period, together with a population-based study of GJB2 variants. METHODS AND RESULTS: Molecular studies were performed using denaturing High Performance Liquid Chromatograghy (DHPLC) and sequencing of the GJB2 gene. Over the last 3 years we have studied 159 families presenting sensorineural hearing loss, including 84 with non syndromic, stable, bilateral deafness. Thirty families were genotyped with causative mutations. In parallel, we have performed a molecular epidemiology study on more than 3000 dried blood spots and established the frequency of the GJB2 variants in our population. Finally, we have compared the prevalence of the variants in the hearing impaired population with the general population. CONCLUSION: Although a high heterogeneity of sequence variation was observed in patients and controls, the 35delG mutation remains the most common pathogenic mutation in our population. Genetic counseling is dependent on the knowledge of the pathogenicity of the mutations and remains difficult in a number of cases. By comparing the sequence variations observed in hearing impaired patients with those sequence variants observed in general population, from the same ethnic background, we show that the M34T, V37I and R127H variants can not be responsible for profound or severe deafness

Proposta de um protocolo para o processamento de requisitos do cliente em empreendimentos habitacionais de interesse social

Muitos estudos têm apontado a importância do gerenciamento dos requisitos do cliente e as dificuldades para sua implementação na indústria da construção devido à natureza complexa de seus processos. Na habitação de interesse social (HIS), os clientes finais raramente participam diretamente do processo de desenvolvimento do produto (PDP) e, por essa razão, suas necessidades não são normalmente capturadas e convertidas em requisitos, os quais, em conseqüência, não são adequadamente considerados pela equipe de projeto. Isso requer mudanças importantes na forma como o processo de desenvolvimento do produto é gerenciado. Esse artigo apresenta um estudo sobre o processamento de requisitos de um conjunto de projetos do Programa de Arrendamento Residencial (PAR). Este estudo enfatiza a tarefa de processar os requisitos do cliente nesse contexto baseado na integração de diferentes fontes de dados, com percepções dos diferentes clientes envolvidos no projeto. A principal contribuição desse trabalho foi o desenvolvimento de um protocolo para o processamento de requisitos, que utiliza dispositivos visuais e a ferramenta Casa da Qualidade (CQ), os quais auxiliam no processamento sistematizado de dados de requisitos do cliente

Discovering and linking public omics data sets using the Omics Discovery Index.

Biomedical data are being produced at an unprecedented rate owing to the falling cost of experiments and wider access to genomics, transcriptomics, proteomics and metabolomics platforms1, 2. As a result, public deposition of omics data is on the increase. This presents new challenges, including finding ways to store, organize and access different types of biomedical data stored on different platforms. Here, we present the Omics Discovery Index (OmicsDI; http://www.omicsdi.org), an open-source platform that enables access, discovery and dissemination of omics data sets

Proteogenomic and metabolomic characterization of human glioblastoma

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment. Wang et al. perform integrated proteogenomic analysis of adult glioblastoma (GBM), including metabolomics, lipidomics, and single nuclei RNA-Seq, revealing insights into the immune landscape of GBM, cell-specific nature of EMT signatures, histone acetylation in classical GBM, and the existence of signaling hubs which could provide therapeutic vulnerabilities