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Biology subjects

Makky, A.

Publications and source records attributed to Makky, A..

2 recordsLinked to original sources

ROSIE: AI generation of multiplex immunofluorescence staining from histopathology images

Hematoxylin and eosin (H&E) is a common and inexpensive histopathology assay. Though widely used and information-rich, it cannot directly inform about specific molecular markers, which require additional experiments to assess. To address this gap, we present ROSIE, a deep-learning framework that computationally imputes the expression and localization of dozens of proteins from H&E images. Our model is trained on a dataset of over 1000 paired and aligned H&E and multiplex immunofluorescence (mIF) samples from 20 tissues and disease conditions, spanning over 16 million cells. Validation of our in silico mIF staining method on held-out H&E samples demonstrates that the predicted biomarkers are effective in identifying cell phenotypes, particularly distinguishing lymphocytes such as B cells and T cells, which are not readily discernible with H&E staining alone. Additionally, ROSIE facilitates the robust identification of stromal and epithelial microenvironments and immune cell subtypes like tumor-infiltrating lymphocytes (TILs), which are important for understanding tumor-immune interactions and can help inform treatment strategies in cancer research.

pathology↗

S3-CIMA: Supervised spatial single-cell image analysis for the identification of disease-associated cell type compositions in tissue

The spatial organization of various cell types within the tissue microenvironment is a key element for the formation of physiological and pathological processes, including cancer and autoimmune diseases. Here, we present S3-CIMA, a weakly supervised convolutional neural network model that enables the detection of disease-specific microenvironment compositions from high-dimensional proteomic imaging data. We demonstrate the utility of this approach by determining cancer outcome- and cellular signaling-specific spatial cell state compositions in highly multiplexed fluorescence microscopy data of the tumor microenvironment in colorectal cancer. Moreover, we use S3-CIMA to identify disease onset-specific changes of the pancreatic tissue microenvironment in type 1 diabetes using imaging mass cytometry data. We evaluated S3-CIMA as a powerful tool to discover novel disease-associated spatial cellular interactions from currently available and future spatial biology datasets.

bioinformatics↗