Dalmolin, Rodrigo Juliani SiqueiraReis, Clóvis Ferreira dos2019-12-172019-12-172019-11-01REIS, Clóvis Ferreira dos. Análise baseada em biologia de sistemas de dados transcricionais de células progenitoras neurais humanas tratadas com chumbo. 2019. 112f. Tese (Doutorado em Bioinformática) - Instituto Metrópole Digital, Universidade Federal do Rio Grande do Norte, Natal, 2019.https://repositorio.ufrn.br/jspui/handle/123456789/28206The consequences of lead poisoning are diverse and relevant to human health. Reaching all organ systems, it mainly affects the nervous system, with severe and irreversible implications of neurodevelopment, memory consolidation, and learning processes in children. They interact with cellular components in many ways, affecting ion-binding proteins, transduction signaling proteins, transmembrane ion channels, and transcription factors. If in one hand, the symptoms of lead poisoning are well known, on the other hand, we have a lack of the systemic effects and its impact on neuronal cell transcription modulation. In order to investigate such effects from a systems biology perspective, we applied the transcriptogramer R/Bioconductor package pipeline to evaluate the transcriptional profile of lead acetatetreated human neural progenitor cells (NPCs) 30µM for 26 days. The transcriptogramer algorithm is designed to identify functionally associated and differentially expressed gene groups in case-control experiments in an unsupervised way. It was able to identify eleven differentially expressed clusters between days 3 and 11 of the lead treatment. Of these, seven presented negative regulation of several cellular systems involved in cell differentiation, such as cytoskeleton organization, RNA and protein biosynthesis, characterized by large and tightly connected networks. The four clusters that were positively regulated presented sparse and poorly connected nodes, mainly related to transcription, transmembrane transport, and signal transduction. In the subsequent period, involving days 12 to 26 of treatment, it was possible to observe a massive alteration of the cellular transcription profile with interference in all layers of gene expression regulation. Thus, our results suggest that lead induces significant transcriptional modifications in NPCs which can be correlated to damage and/or adaptations of various systems, all resulting from intoxication by this heavy metal, thus influencing the result of ES-NP cell differentiation.Acesso AbertoExposição ao chumboTranscriptogramerRNA-SeqAnálise de transcriptomaTime seriesInferência de redesData integrationVisualização de redesdoctoralThesisCNPQ::CIENCIAS BIOLOGICAS