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De Voeght, A.

Publications and source records attributed to De Voeght, A..

2 recordsLinked to original sources

Generative cell phenotyping with structured latent populations

Flow cytometry produces high-dimensional single-cell protein measurements central to immunophenotyp ing and clinical monitoring. Yet analysis still relies largely on manual gating, which is labour-intensive, poorly reproducible, and ill-suited to large marker panels. Existing computational approaches address classification or discovery in isolation, treating cell-type identity as a post-hoc annotation rather than as part of the generative model itself. We present MARVIN, a semi-supervised variational autoencoder that encodes the assumption that cells organise into discrete populations with continuous intra-population variability through a Gaussian mixture prior in the latent space. Because each component represents a distinct cell population, classification, discovery, and density estimation emerge as complementary views of the same representation. On public benchmarks, MARVIN matches or exceeds existing methods using as few as 10% labelled cells. Trained exclusively on healthy samples, it identifies leukaemic cells through elevated reconstruction error, providing an unsupervised anomaly detection signal. On paired stimulation data, it maintains stable population assignments while capturing condition-specific shifts in abundance and marker expression at patient-level resolution. MARVIN is open-source and designed for local deployment, adapting to institution-specific panels and instruments.

bioinformatics↗

Biases introduced by Ficoll-based isolation in acute myeloid leukemia sample analyses support the use of hemolysis

Acute myeloid leukemia (AML) is a heterogeneous malignancy whose characterization relies on immunophenotyping and molecular profiling. While hemolysis is recommended for leukocyte isolation in clinical diagnostics, Ficoll-based density gradient centrifugation is widely used in research and biobanking. Here, we evaluated the impact of Ficoll isolation on commonly performed analyses of AML samples. Ficoll altered flow cytometry-based characterization by systematically enriching lymphocytes and AML blasts while depleting granulocytes. The increased T-cell content impaired AML engraftment in NSG mice, as T cells mediated terminal graft-versus-host disease. Although Ficoll had minimal impact on ex vivo AML blast expansion or chemotherapy response, RNA sequencing identified 1,136 differentially expressed genes compared with hemolysis, with Ficoll-processed samples notably leading to an overestimation of leukemic stem cell gene set expression. Immunogenomic deconvolution highlighted that Ficoll leads to an overestimation of CD8+ T-cell and monocyte abundances in sequenced samples. Mutation calling from RNA-seq data revealed substantial discrepancies between methods, including failure to detect a clinically relevant DNMT3A R882 mutation in a Ficoll-processed sample. Together, these findings support the systematic use of hemolysis to preserve cellular diversity and avoid unpredictable biases introduced by Ficoll-based isolation.

cell biology↗