A5063639001- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Gene expression and cancer classification
- Advanced Fluorescence Microscopy Techniques
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- Cell Image Analysis Techniques
- AI in cancer detection
- Cancer Research and Treatments
- Research in Social Sciences
University of Helsinki
2021-2025
Helsinki University Hospital
2021
The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation the BRCA1/2 genes. We aimed discover how shape cellular phenotypes and spatial interactions tumor microenvironment. Using a highly multiplex immunofluorescence image analysis we generate proteomic data for 21 markers 124,623 single cells from 112 cores originating 31 tumors with mutation (BRCA1/2mut), 13 without alterations HR...
Abstract Motivation Multiplexed imaging and single-cell analysis are increasingly applied to investigate the tissue spatial ecosystems in cancer other complex diseases. Accurate phenotyping based on marker combinations is a critical but challenging task due (i) low reproducibility across experiments with manual thresholding, and, (ii) labor-intensive ground-truth expert annotation required for learning-based methods. Results We developed Tribus, an interactive knowledge-based classifier...
Abstract Motivation Multiplexed imaging and single-cell analysis are increasingly applied to investigate the tissue spatial ecosystems in cancer other complex diseases. Accurate phenotyping based on marker combinations is a critical but challenging task due (i) low reproducibility across experiments with manual thresholding, and, (ii) labor-intensive ground-truth expert annotation required for learning-based methods. Results We developed Tribus, an interactive knowledge-based classifier...
Abstract Background & objective: High grade serous ovarian cancer (HGSC) is the most lethal type of malignancies. Around 50% HGSCs are DNA-repair homologous recombination deficient (HRD) and 15% have CCNE1 gene amplification. Previous results shown that tumor microenvironment (TME) can impact clinical prognosis in HGSC. In this study our objective was to characterize interplay TME with HRD amplification HGSC its association outcomes. Materials methods: We collected spatial protein...
Abstract Introduction: Multiplexed imaging at single-cell resolution is becoming widely used to decipher the role of cellular microenvironment in cancer and other complex diseases. To identify spatial patterns single cells on a tissue, accurate cell-type phenotyping crucial step. We present Tribus, an interactive, semi-supervised classifier that avoids thresholds manual labeling, with user-friendly visualization results automated quality control reports. Materials Methods: developed...
The tumor microenvironment (TME) is a complex network of interactions between malignant and host cells, yet its orchestration in advanced high-grade serous ovarian carcinoma (HGSC) remains poorly understood. We present comprehensive single-cell spatial atlas 280 metastatic HGSCs, integrating high-dimensional imaging, genomics, transcriptomics. Using 929 maps, we identify distinct domains associated with phenotypically heterogeneous cellular compositions, demonstrate that immune cell...
Abstract Background Recent advances in highly-multiplexed tissue technologies and image analysis tools have enabled a more detailed investigation of the tumor microenvironment (TME) its spatial features, including tertiary lymphoid structures (TLSs), at single-cell resolution. TLSs play major part antitumor immune responses, however, their role immunity ovarian cancer remains largely unexplored. Methods In this study, we generated comprehensive atlas by extracting topology information from...
Abstract The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation the BRCA1/2 genes. We aimed discover how shape cellular phenotypes and spatial interactions tumor microenvironment. Using a highly multiplex immunofluorescence image analysis we generated proteomic data for 21 markers 124,623 single cells from 112 cores originating 31 tumors with mutation (BRCA1/2mut), 13 without...
Abstract The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation the BRCA1/2 genes. We aimed discover how shape cellular phenotypes and spatial interactions tumor microenvironment. Using a highly multiplex immunofluorescence image analysis on 112 cores we generated single-cell data for 21 markers 124,623 single cells from 31 tumors with mutation (BRCA1/2mut), 13 without any...
Abstract Immune checkpoint blockade has emerged as a new therapeutic approach for multiple cancers. The majority of high-grade serous ovarian, fallopian tube or peritoneal cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, typically due to mutations hypermethylation BRCA1 BRCA2 genes. A detailed understanding how tumor genotypes affect the microenvironment is unknown. We performed single-cell spatial analysis using highly multiplex tissue cyclic immunofluorescence...