Computational flow cytometry as a diagnostic tool in suspected‐myelodysplastic syndromes

The diagnostic work‐up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected‐MDS. The computationa...

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Published inCytometry. Part A Vol. 99; no. 8; pp. 814 - 824
Main Authors Duetz, Carolien, Van Gassen, Sofie, Westers, Theresia M., Spronsen, Margot F., Bachas, Costa, Saeys, Yvan, Loosdrecht, Arjan A.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.08.2021
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Abstract The diagnostic work‐up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected‐MDS. The computational diagnostic workflow consists of methods for pre‐processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient).
AbstractList The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected-MDS. The computational diagnostic workflow consists of methods for pre-processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient).
The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected-MDS. The computational diagnostic workflow consists of methods for pre-processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient).The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected-MDS. The computational diagnostic workflow consists of methods for pre-processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient).
Author Loosdrecht, Arjan A.
Van Gassen, Sofie
Saeys, Yvan
Westers, Theresia M.
Duetz, Carolien
Spronsen, Margot F.
Bachas, Costa
AuthorAffiliation 2 VIB Inflammation Research Center Ghent University Ghent Belgium
3 Department of Applied Mathematics, Computer Science and Statistics Ghent University Ghent Belgium
1 Department of Hematology, Amsterdam UMC VU University Medical Center, Cancer Center Amsterdam Amsterdam Netherlands
AuthorAffiliation_xml – name: 3 Department of Applied Mathematics, Computer Science and Statistics Ghent University Ghent Belgium
– name: 2 VIB Inflammation Research Center Ghent University Ghent Belgium
– name: 1 Department of Hematology, Amsterdam UMC VU University Medical Center, Cancer Center Amsterdam Amsterdam Netherlands
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Issue 8
Keywords hematological malignancies
flow cytometry
machine learning
diagnostic test
myelodysplastic syndromes
Language English
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2021 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.
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Notes Funding information
Yvan Saeys and Arjan A. van de Loosdrecht contributed equally to this work.
European Union's Horizon 2020 research and innovation programme, Grant/Award Number: 634789
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Snippet The diagnostic work‐up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this...
The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this...
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SubjectTerms Bone marrow
Computer applications
Cytogenetics
diagnostic test
Disorders
Flow cytometry
hematological malignancies
Learning algorithms
Machine learning
Morphology
Myelodysplastic syndrome
myelodysplastic syndromes
Original
Sensitivity
Software
Tubes
Workflow
Title Computational flow cytometry as a diagnostic tool in suspected‐myelodysplastic syndromes
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcyto.a.24360
https://www.ncbi.nlm.nih.gov/pubmed/33942494
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https://www.proquest.com/docview/2522189188
https://pubmed.ncbi.nlm.nih.gov/PMC8453916
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