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Tviblindi algorithm identifies branching developmental trajectories of human B-cell development and describes abnormalities in RAG-1 and WAS patients
M. Bakardjieva, O. Pelák, M. Wentink, H. Glier, D. Novák, J. Stančíková, D. Kužílková, E. Mejstříková, I. Janowska, M. Rizzi, M. van der Burg, J. Stuchlý, T. Kalina
Jazyk angličtina Země Německo
Typ dokumentu časopisecké články
Grantová podpora
23-05561S
The Czech Science Foundation
23-07-00170
Czech Health Research Council
LX22NPO5102
European Union - Next Generation EU (Czech Recovery Plan) - Project National Cancer Research Institute
1S40421N
FWO (Fonds Wetenschappelijk Onderzoek
NLK
Medline Complete (EBSCOhost)
od 2012-06-01 do Před 1 rokem
Wiley Free Content
od 1998 do Před 1 rokem
PubMed
39235410
DOI
10.1002/eji.202451004
Knihovny.cz E-zdroje
- MeSH
- algoritmy * MeSH
- B-lymfocyty * imunologie MeSH
- buněčná diferenciace * imunologie genetika MeSH
- homeodoménové proteiny * genetika metabolismus MeSH
- lidé MeSH
- mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Detailed knowledge of human B-cell development is crucial for the proper interpretation of inborn errors of immunity and malignant diseases. It is of interest to understand the kinetics of protein expression changes during development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human samples from healthy individuals with the aim of describing all B-cell developmental trajectories. We validated a 30-parameter mass cytometry panel and demonstrated the utility of "vaevictis" visualization of B-cell developmental stages. We used the trajectory inference tool "tviblindi" to exhaustively describe all trajectories leading to all developmental ends discovered in the data. Focusing on Natural Effector B cells, we demonstrated the dynamics of expression of nuclear factors (PAX-5, TdT, Ki-67, Bcl-2), cytokine and chemokine receptors (CD127, CXCR4, CXCR5) in relation to the canonical B-cell developmental stage markers. We observed branching of the memory development, where follicular memory formation was marked by CD73 expression. Lastly, we performed an analysis of two example cases of abnormal B-cell development caused by mutations in RAG-1 and Wiskott-Aldrich syndrome gene in patients with primary immunodeficiency. In conclusion, we developed, validated, and presented a comprehensive set of tools for the investigation of B-cell development in the bone marrow compartment.
Data Mining and Modeling for Biomedicine Center for Inflammation Research VIB UGent Ghent Belgium
Department of Applied Mathematics Computer Science and Statistics Ghent University Ghent Belgium
Department of Paediatric Haematology and Oncology University Hospital Motol Prague Czech Republic
Citace poskytuje Crossref.org
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