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Biology subjects

Shaban, M.

Publications and source records attributed to Shaban, M..

4 recordsLinked to original sources

Epstein-Barr Virus Orchestrates Spatial Reorganization and Immunomodulation within the Classic Hodgkin Lymphoma Tumor Microenvironment

Classic Hodgkin Lymphoma (cHL) is a tumor composed of rare malignant Hodgkin and Reed-Sternberg (HRS) cells nested within a T-cell rich inflammatory immune infiltrate. cHL is associated with Epstein-Barr Virus (EBV) in 25% of cases. The specific contributions of EBV to the pathogenesis of cHL remain largely unknown, in part due to technical barriers in dissecting the tumor microenvironment (TME) in high detail. Herein, we applied multiplexed ion beam imaging (MIBI) spatial pro-teomics on 6 EBV-positive and 14 EBV-negative cHL samples. We identify key TME features that distinguish between EBV-positive and EBV-negative cHL, including the relative predominance of memory CD8 T cells and increased T-cell dysfunction as a function of spatial proximity to HRS cells. Building upon a larger multi-institutional cohort of 22 EBV-positive and 24 EBV-negative cHL samples, we orthogonally validated our findings through a spatial multi-omics approach, coupling whole transcriptome capture with antibody-defined cell types for tu-mor and T-cell populations within the cHL TME. We delineate contrasting transcriptomic immunological signatures between EBV-positive and EBV-negative cases that differently impact HRS cell proliferation, tumor-immune interactions, and mecha-nisms of T-cell dysregulation and dysfunction. Our multi-modal framework enabled a comprehensive dissection of EBV-linked reorganization and immune evasion within the cHL TME, and highlighted the need to elucidate the cellular and molecular fac-tors of virus-associated tumors, with potential for targeted therapeutic strategies.

cancer biology↗

Deep Learning Model Imputes Missing Stains in Multiplex Images

Multiplex staining enables simultaneous detection of multiple protein markers within a tissue sample. However, the increased marker count increased the likelihood of staining and imaging failure, leading to higher resource usage in multiplex staining and imaging. We address this by proposing a deep learning-based MArker imputation model for multipleX IMages (MAXIM) that accurately impute protein markers by leveraging latent biological relationships between markers. The models imputation ability is extensively evaluated at pixel and cell levels across various cancer types. Additionally, we present a comparison between imputed and actual marker images within the context of a downstream cell classification task. The MAXIM models interpretability is enhanced by gaining insights into the contribution of individual markers in the imputation process. In practice, MAXIM can reduce the cost and time of multiplex staining and image acquisition by accurately imputing protein markers affected by staining issues.

pathology↗

MAPS: Pathologist-level cell type annotation from tissue images through machine learning

Highly multiplexed protein imaging is emerging as a potent technique for analyzing protein distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive and necessitate iterative expert input, thereby constraining their scalability and practicality for extensive datasets. We introduce MAPS (Machine learning for Analysis of Proteomics in Spatial biology), a machine learning approach facilitating rapid and precise cell type identification with human-level accuracy from spatial proteomics data. Validated on multiple in-house and publicly available MIBI and CODEX datasets, MAPS outperforms current annotation techniques in terms of speed and accuracy, achieving pathologist-level precision even for challenging cell types, including tumor cells of immune origin. By democratizing rapidly deployable and scalable machine learning annotation, MAPS holds significant potential to expedite advances in tissue biology and disease comprehension.

cancer biology↗

Object-Attribute Biclustering for Elimination of Missing Genotypes in Ischemic Stroke Genome-Wide Data

Missing genotypes can affect the efficacy of machine learning approaches to identify the risk genetic variants of common diseases and traits. The problem occurs when genotypic data are collected from different experiments with different DNA microarrays, each being characterised by its pattern of uncalled (missing) genotypes. This can prevent the machine learning classifier from assigning the classes correctly. To tackle this issue, we used well-developed notions of object-attribute biclusters and formal concepts that correspond to dense subrelations in the binary relation patients x SNPs. The paper contains experimental results on applying a biclustering algorithm to a large real-world dataset collected for studying the genetic bases of ischemic stroke. The algorithm could identify large dense biclusters in the genotypic matrix for further processing, which in return significantly improved the quality of machine learning classifiers. The proposed algorithm was also able to generate biclusters for the whole dataset without size constraints in comparison to the In-Close4 algorithm for generation of formal concepts.

bioinformatics↗