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1.
Nucleic Acids Res ; 52(D1): D1138-D1142, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37933860

RESUMO

BloodSpot is a specialised database integrating gene expression data from acute myeloid leukaemia (AML) patients related to blood cell development and maturation. The database and interface has helped numerous researchers and clinicians to quickly get an overview of gene expression patterns in healthy and malignant haematopoiesis. Here, we present an update to our framework that includes protein expression data of sorted single cells. With this update we also introduce datasets broadly spanning age groups, which many users have requested, with particular interest for researchers studying paediatric leukaemias. The backend of the database has been rewritten and migrated to a cloud-based environment to accommodate the growth, and provide a better user-experience for our many international users. Users can now enjoy faster transfer speeds and a more responsive interface. In conclusion, the continuing popularity of the database and emergence of new data modalities has prompted us to rewrite and futureproof the back-end, including paediatric centric views, as well as single cell protein data, allowing us to keep the database updated and relevant for the years to come. The database is freely available at www.bloodspot.eu.


Assuntos
Hematopoese , Leucemia Mieloide Aguda , Criança , Humanos , Células Sanguíneas , Diferenciação Celular , Bases de Dados Genéticas , Hematopoese/genética , Leucemia Mieloide Aguda/genética , Proteínas/genética
2.
Angew Chem Int Ed Engl ; 58(47): 16943-16951, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31573131

RESUMO

Stem-cell behavior is regulated by the material properties of the surrounding extracellular matrix, which has important implications for the design of tissue-engineering scaffolds. However, our understanding of the material properties of stem-cell scaffolds is limited to nanoscopic-to-macroscopic length scales. Herein, a solid-state NMR approach is presented that provides atomic-scale information on complex stem-cell substrates at near physiological conditions and at natural isotope abundance. Using self-assembled peptidic scaffolds designed for nervous-tissue regeneration, we show at atomic scale how scaffold-assembly degree, mechanics, and homogeneity correlate with favorable stem cell behavior. Integration of solid-state NMR data with molecular dynamics simulations reveals a highly ordered fibrillar structure as the most favorable stem-cell scaffold. This could improve the design of tissue-engineering scaffolds and other self-assembled biomaterials.


Assuntos
Materiais Biocompatíveis/química , Matriz Extracelular , Nanofibras/química , Células-Tronco Neurais/citologia , Medicina Regenerativa , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Humanos , Microscopia de Força Atômica , Fragmentos de Peptídeos/química
3.
Sci Rep ; 10(1): 20465, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33235258

RESUMO

The outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all of its overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested NetMHC suite tools' predictions by using an in vitro peptide-MHC stability assay. We assessed 777 peptides that were predicted to be good binders across 11 MHC alleles in a complex-stability assay and tested a selection of 19 epitope-HLA-binding prediction tools against the assay. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allele in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA alleles. Our findings may contribute to the design of an efficacious vaccine against COVID-19.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Biologia Computacional/métodos , Epitopos de Linfócito T/imunologia , Aprendizado de Máquina , SARS-CoV-2/imunologia , Alelos , Sequência de Bases , COVID-19/virologia , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Peptídeos/genética , Peptídeos/imunologia , Glicoproteína da Espícula de Coronavírus/genética
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