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Unsupervised cluster analysis and subset characterization of abnormal erythropoiesis using the bioinformatic Flow-Self Organizing Maps algorithm

Porwit, Anna LU ; Violidaki, Despoina LU orcid ; Axler, Olof LU ; Lacombe, Francis ; Ehinger, Mats LU and Béné, Marie C (2022) In Cytometry Part B - Clinical Cytometry 102(2). p.134-142
Abstract

BACKGROUND: The Flow-Self Organizing Maps (FlowSOM) artificial intelligence (AI) program, available within the Bioconductor open-source R-project, allows for an unsupervised visualization and interpretation of multiparameter flow cytometry (MFC) data.

METHODS: Applied to a reference merged file from 11 normal bone marrows (BM) analyzed with an MFC panel targeting erythropoiesis, FlowSOM allowed to identify six subpopulations of erythropoietic precursors (EPs). In order to find out how this program would help in the characterization of abnormalities in erythropoiesis, MFC data from list-mode files of 16 patients (5 with non-clonal anemia and 11 with myelodysplastic syndrome [MDS] at diagnosis) were analyzed.

RESULTS:... (More)

BACKGROUND: The Flow-Self Organizing Maps (FlowSOM) artificial intelligence (AI) program, available within the Bioconductor open-source R-project, allows for an unsupervised visualization and interpretation of multiparameter flow cytometry (MFC) data.

METHODS: Applied to a reference merged file from 11 normal bone marrows (BM) analyzed with an MFC panel targeting erythropoiesis, FlowSOM allowed to identify six subpopulations of erythropoietic precursors (EPs). In order to find out how this program would help in the characterization of abnormalities in erythropoiesis, MFC data from list-mode files of 16 patients (5 with non-clonal anemia and 11 with myelodysplastic syndrome [MDS] at diagnosis) were analyzed.

RESULTS: Unsupervised FlowSOM analysis identified 18 additional subsets of EPs not present in the merged normal BM samples. Most of them involved subtle unexpected and previously unreported modifications in CD36 and/or CD71 antigen expression and in side scatter characteristics. Three patterns were observed in MDS patient samples: i) EPs with decreased proliferation and abnormal proliferating precursors, ii) EPs with a normal proliferating fraction and maturation defects in late precursors, and iii) EPs with a reduced erythropoietic fraction but mostly normal patterns suggesting that erythropoiesis was less affected. Additionally, analysis of sequential samples from an MDS patient under treatment showed a decrease of abnormal subsets after azacytidine treatment and near normalization after allogeneic hematopoietic stem-cell transplantation.

CONCLUSION: Unsupervised clustering analysis of MFC data discloses subtle alterations in erythropoiesis not detectable by cytology nor FCM supervised analysis. This novel AI analytical approach sheds some new light on the pathophysiology of these conditions.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cytometry Part B - Clinical Cytometry
volume
102
issue
2
pages
134 - 142
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85124560061
  • pmid:35150187
ISSN
1552-4949
DOI
10.1002/cyto.b.22059
language
English
LU publication?
yes
additional info
© 2022 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.
id
68093df7-d11c-4dbc-920a-448c6e3341bd
date added to LUP
2022-03-21 13:25:09
date last changed
2024-06-21 16:55:17
@article{68093df7-d11c-4dbc-920a-448c6e3341bd,
  abstract     = {{<p>BACKGROUND: The Flow-Self Organizing Maps (FlowSOM) artificial intelligence (AI) program, available within the Bioconductor open-source R-project, allows for an unsupervised visualization and interpretation of multiparameter flow cytometry (MFC) data.</p><p>METHODS: Applied to a reference merged file from 11 normal bone marrows (BM) analyzed with an MFC panel targeting erythropoiesis, FlowSOM allowed to identify six subpopulations of erythropoietic precursors (EPs). In order to find out how this program would help in the characterization of abnormalities in erythropoiesis, MFC data from list-mode files of 16 patients (5 with non-clonal anemia and 11 with myelodysplastic syndrome [MDS] at diagnosis) were analyzed.</p><p>RESULTS: Unsupervised FlowSOM analysis identified 18 additional subsets of EPs not present in the merged normal BM samples. Most of them involved subtle unexpected and previously unreported modifications in CD36 and/or CD71 antigen expression and in side scatter characteristics. Three patterns were observed in MDS patient samples: i) EPs with decreased proliferation and abnormal proliferating precursors, ii) EPs with a normal proliferating fraction and maturation defects in late precursors, and iii) EPs with a reduced erythropoietic fraction but mostly normal patterns suggesting that erythropoiesis was less affected. Additionally, analysis of sequential samples from an MDS patient under treatment showed a decrease of abnormal subsets after azacytidine treatment and near normalization after allogeneic hematopoietic stem-cell transplantation.</p><p>CONCLUSION: Unsupervised clustering analysis of MFC data discloses subtle alterations in erythropoiesis not detectable by cytology nor FCM supervised analysis. This novel AI analytical approach sheds some new light on the pathophysiology of these conditions.</p>}},
  author       = {{Porwit, Anna and Violidaki, Despoina and Axler, Olof and Lacombe, Francis and Ehinger, Mats and Béné, Marie C}},
  issn         = {{1552-4949}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{134--142}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Cytometry Part B - Clinical Cytometry}},
  title        = {{Unsupervised cluster analysis and subset characterization of abnormal erythropoiesis using the bioinformatic Flow-Self Organizing Maps algorithm}},
  url          = {{http://dx.doi.org/10.1002/cyto.b.22059}},
  doi          = {{10.1002/cyto.b.22059}},
  volume       = {{102}},
  year         = {{2022}},
}