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Argy, N.

Publications and source records attributed to Argy, N..

2 recordsLinked to original sources

Revealing invisible cell phenotypes with conditional generative modeling

Biological sciences, drug discovery and medicine rely heavily on cell phenotype perturbation and observation. Aside from dramatic events such as cell division or cell death, most cell phenotypic changes that keep cells alive are subtle and thus hidden from us by natural cell variability: two cells in the same condition already look different. While we show that deep learning models can leverage invisible features from microscopy images, to discriminate between close conditions, these features can yet hardly be observed and therefore interpreted. In this work, we show that conditional generative models can be used to transform an image of cells from any one condition to another, thus canceling cell variability. We visually and quantitatively validate that the principle of synthetic cell perturbation works on discernible cases such as high concentration drug treatments, nuclear translocation and golgi apparatus assays. We then illustrate its effectiveness in displaying otherwise invisible cell phenotypes triggered by blood cells under parasite infection, the presence of a disease-causing pathological mutation in differentiated neurons derived from iPSCs or low concentration drug treatments. The proposed approach, easy to use and robust, opens the door to the accessible discovery of biological and disease biomarkers.

bioinformatics↗

Transcriptome analysis of Plasmodium falciparum isolates from Benin reveals specific gene expression associated with cerebral malaria

The host and parasitic factors leading to cerebral malaria (CM) are not yet fully elucidated and CM Plasmodium falciparum isolates transcriptome profile remains largely unknown. Based on RNA-seq data from 15 CM and 15 uncomplicated malaria (UM) children from Benin, we identified an increased ring stage signature in CM parasites. Reduced circulating time may result from a higher adherence ability of CM isolates and consistent with this hypothesis, we measured an overexpression of var genes in CM. var genes domains expression was more restricted in CM isolates compared to UM, reflecting the specific binding to receptors in host brain endothelium capillaries. However, ICAM-1 binding motif was found expressed in both CM and UM, questioning its role in PfEMP1 adhesion to ICAM-1 receptor. UM isolates increased circulation time may also be modulated by a more efficient immune response against infected erythrocytes surface proteins, which we could not demonstrate on our cohort. Identification of deregulated genes involved in adhesion, excluding variant surface antigens, also supports the hypothesis of an increased CM adhesion capacity. Finally, numerous upregulated genes involved in entry into host pathway were found, reflecting a greater erythrocytes invasion capacity of CM parasites.

genomics↗