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Deep learning enables spatial mapping of the mosaic microenvironment of myeloma bone marrow trephine biopsies

Hagos, Yeman B; Lecat, Catherine SY; Patel, Dominic; Mikolajczak, Anna; Castillo, Simon P; Lyon, Emma J; Foster, Kane; ... Yuan, Yinyin; + view all (2023) Deep learning enables spatial mapping of the mosaic microenvironment of myeloma bone marrow trephine biopsies. Cancer Research 10.1158/0008-5472.can-22-2654. Green open access

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Abstract

Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphological, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images. MoSaicNet and AwareNet achieved an area under the curve of >0.98 for tissue and cellular classification on separate test datasets. Application of MoSaicNet and AwareNet enabled investigation of bone heterogeneity and thickness as well as spatial histology analysis of bone marrow trephine samples from monoclonal gammopathies of undetermined significance (MGUS) and from paired newly diagnosed and post-treatment multiple myeloma. The most significant difference between MGUS and newly diagnosed multiple myeloma (NDMM) samples was not related to cell density but to spatial heterogeneity, with reduced spatial proximity of BLIMP1+ tumor cells to CD8+ cells in MGUS compared with NDMM samples. Following treatment of multiple myeloma patients, there was a reduction in the density of BLIMP1+ tumor cells, effector CD8+ T cells, and T regulatory cells, indicative of an altered immune microenvironment. Finally, bone heterogeneity decreased following treatment of MM patients. In summary, deep-learning based spatial mapping of bone marrow trephine biopsies can provide insights into the cellular topography of the myeloma marrow microenvironment and complement aspirate-based techniques.

Type: Article
Title: Deep learning enables spatial mapping of the mosaic microenvironment of myeloma bone marrow trephine biopsies
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/0008-5472.can-22-2654
Publisher version: https://doi.org/10.1158/0008-5472.CAN-22-2654
Language: English
Additional information: This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license
Keywords: Multiple myeloma; bone marrow trephine; deep learning; spatial analysis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10181436
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