Viktoria Bojilova
A5082886062- Gastric Cancer Management and Outcomes
- Esophageal Cancer Research and Treatment
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Metastasis and carcinoma case studies
- Single-cell and spatial transcriptomics
- Radiomics and Machine Learning in Medical Imaging
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- Cell Image Analysis Techniques
- Hematopoietic Stem Cell Transplantation
- Evolution and Genetic Dynamics
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Genomics and Phylogenetic Studies
- Shoulder Injury and Treatment
- T-cell and B-cell Immunology
- Nerve Injury and Rehabilitation
- Genetic factors in colorectal cancer
- Shoulder and Clavicle Injuries
- Ferroptosis and cancer prognosis
- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- CAR-T cell therapy research
Memorial Sloan Kettering Cancer Center
2019-2023
Memorial Hospital
2023
Kettering University
2022
University of British Columbia
2018-2019
Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, open source computational methods. Using we generated resource 51,926 matched cell images diverse types including lines, xenografts, diagnostic samples with limited...
Abstract High-grade serous ovarian cancer (HGSOC) is an archetypal of genomic instability 1–4 patterned by distinct mutational processes 5,6 , tumour heterogeneity 7–9 and intraperitoneal spread 7,8,10 . Immunotherapies have had limited efficacy in HGSOC 11–13 highlighting unmet need to assess how the anatomical sites foci determine immunological states microenvironment. Here we carried out integrative analysis whole-genome sequencing, single-cell RNA digital histopathology multiplexed...
How cell-to-cell copy number alterations that underpin genomic instability
We report updated clinical outcomes from a phase II study of pembrolizumab, trastuzumab, and chemotherapy (PTC) in metastatic esophagogastric cancer conjunction with an independent Memorial Sloan Kettering (MSK) cohort.
Abstract Deciphering individual cell phenotypes from cell-specific transcriptional processes requires high dimensional single RNA sequencing. However, current dimensionality reduction methods aggregate sparse gene information across cells, without directly measuring the relationships that exist between genes. By performing with respect to co-expression, low-dimensional features can model these gene-specific and leverage shared signal overcome sparsity. We describe GeneVector, a scalable...
Although allogeneic hematopoietic cell transplant (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of posttransplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape graft-versus-leukemia effect, we evaluated immune signatures at diagnosis and in bone marrow samples from 4 patients using a multimodal single-cell proteogenomic approach. Downregulation major histocompatibility complex class II...
Summary Essential features of cancer tissue cellular heterogeneity such as negatively selected genome topologies, sub-clonal mutation patterns and replication states can only effectively be studied by sequencing single-cell genomes at scale high fidelity. Using an amplification-free approach implemented on commodity hardware (DLP+) coupled with a cloud-based computational platform, we define resource 40,000 characterized their states, across wide range types conditions. We show that shallow...
Abstract Deciphering individual cell phenotypes from cell-specific transcriptional processes requires high dimensional single RNA sequencing. However, current dimensionality reduction methods aggregate sparse gene information across cells, without directly measuring the relationships that exist between genes. By performing with respect to co-expression, low-dimensional features can model these gene-specific and leverage shared signal overcome sparsity. We describe GeneVector, a scalable...
ABSTRACT High-grade serous ovarian cancer (HGSOC) is an archetypal of genomic instability patterned by distinct mutational processes, intratumoral heterogeneity and intraperitoneal spread. We investigated determinants immune recognition evasion in HGSOC to elucidate co- evolutionary processes underlying malignant progression tumor immunity. Mutational anatomic sites foci were key microenvironment cellular phenotypes, inferred from whole genome sequencing, single-cell RNA digital...
ABSTRACT Structural genome alterations are determinants of cancer ontogeny and therapeutic response. While bulk sequencing has enabled delineation structural variation (SV) mutational processes which generate patterns DNA damage, we have little understanding how these lead to cell-to-cell variations underlie selection rates accrual different genomic lesions. We analysed 309 high grade serous ovarian triple negative breast genomes determine their processes, selecting 22 from sequenced...
Abstract Cancer genomes exhibit extensive chromosomal copy number changes and structural variation, yet how allele specific alterations drive cancer genome evolution remains unclear. Here, through application of a new computational approach we report in 11,097 single cell whole from genetically engineered mammary epithelial cells 21,852 high grade serous ovarian triple negative breast cancers. Resolving profiles to individual alleles uncovered genomic background distributions gains, losses...
<p>Identifying intratumor clonal selection and associated resistance mechanisms. a, Inferred tumor clones paired pre-treatment post-cycle 2 CAPOX + trastuzumab scRNA-seq demonstrates rapid clearance of highly ERBB2 expression (red) clones, while many lower expressing persisted even expanded. Contraction at the on-treatment timepoint reflects their RECIST response initial follow up imaging timepoint, demonstrating that patient 3, who had highest expression, deepest most durable...
<p>Supplemental Methods</p>
<p>Serial plasma ctDNA in an individual patient demonstrating pre-treatment genomic heterogeneity and selection for resistant clones. Plasma at diagnosis revealed ERBB2 amplification a with HER2+ EG cancer, as well numerous pre-existing resistance mechanisms including EGFR amplification, PIK3CA FGFR3-TACC3 fusion that was not identified on tumor sequencing (Figure 2b).</p>
<p>Baseline biopsies from a patient demonstrating significant intra-patient heterogeneity with diffusely HER2+ and PD-L1– primary tumor HER2– but PD-L1 CPS 100 retroperitoneal lymph node neuroendocrine differentiation.</p>
<p>HER2 heterogeneity and RTK alterations are more frequent among patients with shorter PFS. HER2 testing tissue / plasma ctDNA NGS upon progression demonstrate that 8 of 16 (50%) had negative tumors post-treatment, 2 ERBB2 amplified pre-treatment were non-amplified post-treatment. Additionally, in PI3K, cell cycle proteins, Ras-Raf, EGFR, FGFR1/2, MET found progression, potentially associated treatment resistance.</p>
<p>Survival and response in patients receiving trastuzumab/chemotherapy + PD-1 inhibition on- or off-protocol (n=66). a, Progression-free survival objective rate by cohort. b, Overall cohort.</p>