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Ivan, Z. Z.

Publications and source records attributed to Ivan, Z. Z..

2 recordsLinked to original sources

Subphase-Labeled Mitotic Dataset for AI-powered Cell Division Analysis

Mitosis detection represents a critical task in the field of digital pathology, as determination of the mitotic index (MI) plays an important role in the tumor grading and prognostic assessment of patients. Manual determination of MI is a labor-intensive and time-consuming task for practitioners with rather high interobserver variability, thus, automation has become a priority. There has been substantial progress towards creating robust mitosis detection algorithms in recent years, primarily driven by the Mitosis Domain Generalization (MIDOG) challenges. In parallel, there has been growing interest in the molecular characterization of mitosis with the goal of achieving a more comprehensive understanding of its underlying mechanisms in a subphase-specific manner. Here, we introduce a new mitotic figure dataset annotated with subphase information based on the MIDOG++ dataset as well as a previously unrepresented tumor domain to enhance the diversity and applicability of the dataset. We envision a new perspective for domain generalization by improving the performance of models with subtyping mitotic cells into the 5 main stages of normal mitosis, complemented with an atypical mitotic class. We believe that our work broadens the horizon in digital pathology: subtyping information could provide useful help for mitosis detection, while also providing promising new directions in answering biological questions, such as molecular analysis of the subphases on a single cell level.

bioinformatics↗

A Morpho-Proteomic Atlas of Mitosis at Sub-Minute Resolution

Precise spatiotemporal protein organization is critical for fundamental biological processes including cell division1,2. Indeed, aberrant mitosis and mitotic factors are involved in diverse diseases, including various cancers3,4, Alzheimers disease5, and rare diseases6. During mitosis, complex spatial rearrangements and regulation ensure the accurate separation of replicated sister chromatids to produce genetically identical daughter cells7-9. Previous studies employed high-throughput methodologies to follow specific proteins during mitosis10-15. Still a temporally refined systems-level approach capable of monitoring morphological and proteomic changes throughout mitosis has been lacking. Here, we achieved unprecedented resolution by phenotypically decomposing mitosis into 40 subsections of a regression plane for proteomic analysis using deep learning and regression techniques. Our deep visual proteomics (DVP) workflow16, revealed rapid, dynamic proteomic changes throughout mitosis. We quantified 4,350 proteins with high confidence, demonstrating that 147 show significant dynamic abundance changes during mitotic progression. Clustering revealed coordinated patterns of protein regulation, while network analysis uncovered tight regulation of core cell cycle proteins and a link between cell cycle and cancer-linked mutations. Immunofluorescence validated abundance changes and linked previously uncharacterised proteins, like C19orf53, to mitosis. To facilitate data navigation, we developed Mito-Omix, a user-friendly online platform that integrates intricate morphological and molecular data. Our morphological and proteomic dataset spans mitosis at high resolution, providing a rich resource for understanding healthy and aberrant cell division.

cell biology↗