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Updating TCGA glioma classification through integration of molecular data following the latest WHO guidelines
Publication . de Mendonça, Mónica Leiria; Coletti, Roberta; Gonçalves, Céline S.; Martins, Eduarda P.; Costa, Bruno M.; Vinga, Susana; Lopes, Marta B.; CMA - Centro de Matemática e Aplicações; Faculdade de Ciências e Tecnologia (FCT); UNIDEMI - Unidade de Investigação e Desenvolvimento em Engenharia Mecânica e Industrial; DM - Departamento de Matemática; Nature Research
The understanding of glioma disease has significantly advanced through the application of genetic and molecular profiling techniques on brain tumour tissue. Molecular biomarkers have gained a crucial role in glioma diagnosis, driving groundbreaking changes in the disease classification as standardised by the 2016 and 2021 World Health Organisation (WHO) Classification of Tumours of the Central Nervous System. Recent insights from large-scale multi-omics databases, such as The Cancer Genome Atlas (TCGA), have enriched our comprehension of this cancer type. However, given the evolution of glioma classification, retrospective databases may contain outdated annotations, suboptimal for research. To address this issue, we propose two methods for updating the tumor classification of TCGA glioma samples according to the 2016 and 2021 WHO guidelines, through the integration of open-access curated molecular profiling data. Respectively, our Method-2016 and Method-2021 allowed for the diagnostic update of 98% and 87% of cases. The proposed reclassification pipelines, provided in R scripts, enable straightforward reproduction or customisation upon new WHO guideline releases.
Isolation of acute myeloid leukemia blasts from blood using a microfluidic device
Publication . Teixeira, Alexandra; Sousa-Silva, Maria; Chícharo, Alexandre; Oliveira, Kevin; Moura, André; Carneiro, Adriana; Piairo, Paulina; Águas, Hugo; Sampaio-Marques, Belém; Castro, Isabel; Mariz, José; Ludovico, Paula; Abalde-Cela, Sara; Diéguez, Lorena; DCM - Departamento de Ciência dos Materiais; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); UNINOVA-Instituto de Desenvolvimento de Novas Tecnologias; RSC - Royal Society of Chemistry
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and associated with poor prognosis. Unfortunately, most of the patients that achieve clinical complete remission after the treatment will ultimately relapse due to the persistence of minimal residual disease (MRD), that is not measurable using conventional technologies in the clinic. Microfluidics is a potential tool to improve the diagnosis by providing early detection of MRD. Herein, different designs of microfluidic devices were developed to promote lateral and vertical mixing of cells in microchannels to increase the contact area of the cells of interest with the inner surface of the device. Possible interactions between the cells and the surface were studied using fluid simulations. For the isolation of leukemic blasts, a positive selection strategy was used, targeting the cells of interest using a panel of specific biomarkers expressed in immature and aberrant blasts. Finally, once the optimisation was complete, the best conditions were used to process patient samples for downstream analysis and benchmarking, including phenotypic and genetic characterisation. The potential of these microfluidic devices to isolate and detect AML blasts may be exploited for the monitoring of AML patients at different stages of the disease.
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Fundação para a Ciência e a Tecnologia
Programa de financiamento
Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
Número da atribuição
UIDP/50026/2020