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Unsupervised meta-clustering identifies risk clusters in acute myeloid leukemia based on clinical and genetic profiles.


ABSTRACT:

Background

Increasingly large and complex biomedical data sets challenge conventional hypothesis-driven analytical approaches, however, data-driven unsupervised learning can detect inherent patterns in such data sets.

Methods

While unsupervised analysis in the medical literature commonly only utilizes a single clustering algorithm for a given data set, we developed a large-scale model with 605 different combinations of target dimensionalities as well as transformation and clustering algorithms and subsequent meta-clustering of individual results. With this model, we investigated a large cohort of 1383 patients from 59 centers in Germany with newly diagnosed acute myeloid leukemia for whom 212 clinical, laboratory, cytogenetic and molecular genetic parameters were available.

Results

Unsupervised learning identifies four distinct patient clusters, and statistical analysis shows significant differences in rate of complete remissions, event-free, relapse-free and overall survival between the four clusters. In comparison to the standard-of-care hypothesis-driven European Leukemia Net (ELN2017) risk stratification model, we find all three ELN2017 risk categories being represented in all four clusters in varying proportions indicating unappreciated complexity of AML biology in current established risk stratification models. Further, by using assigned clusters as labels we subsequently train a supervised model to validate cluster assignments on a large external multicenter cohort of 664 intensively treated AML patients.

Conclusions

Dynamic data-driven models are likely more suitable for risk stratification in the context of increasingly complex medical data than rigid hypothesis-driven models to allow for a more personalized treatment allocation and gain novel insights into disease biology.

SUBMITTER: Eckardt JN 

PROVIDER: S-EPMC10192332 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Unsupervised meta-clustering identifies risk clusters in acute myeloid leukemia based on clinical and genetic profiles.

Eckardt Jan-Niklas JN   Röllig Christoph C   Metzeler Klaus K   Heisig Peter P   Stasik Sebastian S   Georgi Julia-Annabell JA   Kroschinsky Frank F   Stölzel Friedrich F   Platzbecker Uwe U   Spiekermann Karsten K   Krug Utz U   Braess Jan J   Görlich Dennis D   Sauerland Cristina C   Woermann Bernhard B   Herold Tobias T   Hiddemann Wolfgang W   Müller-Tidow Carsten C   Serve Hubert H   Baldus Claudia D CD   Schäfer-Eckart Kerstin K   Kaufmann Martin M   Krause Stefan W SW   Hänel Mathias M   Berdel Wolfgang E WE   Schliemann Christoph C   Mayer Jiri J   Hanoun Maher M   Schetelig Johannes J   Wendt Karsten K   Bornhäuser Martin M   Thiede Christian C   Middeke Jan Moritz JM  

Communications medicine 20230517 1


<h4>Background</h4>Increasingly large and complex biomedical data sets challenge conventional hypothesis-driven analytical approaches, however, data-driven unsupervised learning can detect inherent patterns in such data sets.<h4>Methods</h4>While unsupervised analysis in the medical literature commonly only utilizes a single clustering algorithm for a given data set, we developed a large-scale model with 605 different combinations of target dimensionalities as well as transformation and clusteri  ...[more]

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