Keren Isaev
A5004820390- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- RNA modifications and cancer
- RNA Research and Splicing
- Glioma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Lymphoma Diagnosis and Treatment
- Genomics and Phylogenetic Studies
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Genetic factors in colorectal cancer
- Bioinformatics and Genomic Networks
- Evolution and Genetic Dynamics
- Ubiquitin and proteasome pathways
- Medicinal Plant Pharmacodynamics Research
- Chromosomal and Genetic Variations
- Genomics and Rare Diseases
- Medical Imaging and Analysis
- Spine and Intervertebral Disc Pathology
- Nutrition, Genetics, and Disease
- Spinal Fractures and Fixation Techniques
- Genomic variations and chromosomal abnormalities
- Viral-associated cancers and disorders
University Health Network
2017-2024
Princess Margaret Cancer Centre
2017-2024
New York Genome Center
2023-2024
Columbia University
2023-2024
University of Toronto
2017-2023
Ontario Institute for Cancer Research
2017-2023
Centre for Addiction and Mental Health
2017
Mental Health Research Institute
2017
The discovery of drivers cancer has traditionally focused on protein-coding genes
Abstract Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for resource lncRNAs with validated roles. Furthermore, it remains debated whether mutated can drive tumorigenesis, and such functions could be conserved during evolution. Here, as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, we introduce Cancer LncRNA Census (CLC), compilation 122 GENCODE causal roles in phenotypes. In contrast to existing databases, CLC requires...
Multi-omics datasets represent distinct aspects of the central dogma molecular biology. Such high-dimensional profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple using statistical fusion, rationalizes contributing evidence highlights associated genes. As part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing from...
Abstract The catalog of cancer driver mutations in protein-coding genes has greatly expanded the past decade. However, non-coding are less well-characterized and only a handful recurrent mutations, most notably TERT promoter have been reported. Here, as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 across 38 tumor types, we perform multi-faceted pathway network analyses 2583 genomes 27 types compiled by PCAWG...
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute schizophrenia expression.
Glioblastoma is the most common primary brain tumor in adults. While introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid recurrence remains universal. The transcriptional regulatory protein, inhibitor DNA-binding-1 (ID1), a key regulator cell phenotype cancer. We show that CRISPR-mediated knockout ID1 glioblastoma cells, breast adenocarcinoma melanoma cells dramatically reduced progression all three cancer systems through downregulation...
Abstract The discovery of driver mutations is one the key motivations for cancer genome sequencing. Here , as part ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium which aggregated whole sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify in coding non-coding sites within genomes. Using total 1373 genomic features derived public sources, DriverPower’s...
Abstract Discovery of cancer drivers has traditionally focused on the identification protein-coding genes. Here we present a comprehensive analysis putative driver mutations in both and non-coding genomic regions across >2,500 whole genomes from Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium. We developed statistically rigorous strategy for combining significance levels multiple discovery methods demonstrate that integrated results overcome limitations individual methods. combined...
Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes 713 pre-treatment tumor tissue samples. Our analysis revealed existence five with unique profiles that correlated clinicopathological characteristics. The clusters were enriched specific mutations as follows: CS (CREBBP STAT6), TT (TNFAIP3 TP53), GM (GNA13 MEF2B), Q...
Long non-coding RNAs (lncRNAs) are increasingly recognized as functional units in cancer and powerful biomarkers; however, most remain uncharacterized. Here, we analyze 5,592 prognostic lncRNAs 9,446 cancers of 30 types using machine learning. We identify 166 whose expression correlates with survival improves the accuracy common clinical variables, molecular features, subtypes. Prognostic often characterized by switch-like patterns. In low-grade gliomas, HOXA10-AS activation is a robust...
Abstract Purpose: The efficacy of EZH2 inhibition has been modest in the initial clinical exploration diffuse large B-cell lymphoma (DLBCL), yet inhibitors are well tolerated. Herein, we aimed to uncover genetic and pharmacologic opportunities enhance DLBCL. Experimental Design: We conducted a genome-wide sensitizing CRISPR/Cas9 screen with tazemetostat, catalytic inhibitor EZH2. effect IKZF1 loss function was then validated leveraged for combination treatment lenalidomide. RNA sequencing...
In the face of rapidly accumulating genomic data, our understanding RNA regulatory code remains incomplete. Pre-trained foundation models offer an avenue to adapt learned representations biological prediction tasks. However, existing are trained using strategies borrowed from textual or visual domains, such as masked language modelling next token prediction, that do not leverage domain knowledge. Here, we introduce Orthrus, a Mamba-based model pre-trained novel self-supervised contrastive...
Alternative splicing is an essential mechanism for diversifying proteins, in which mature RNA isoforms produce proteins with potentially distinct functions. Two major challenges characterizing the cellular function of are lack experimental methods to specifically and efficiently modulate isoform expression computational tools complex design. To address these gaps, we developed methodically tested a strategy pairs RNA-targeting CRISPR/Cas13d system guide RNAs that span exon-exon junctions...
Abstract A comprehensive catalogue of the mutations that drive tumorigenesis and progression is essential to understanding tumor biology developing therapies. Protein-coding driver have been well-characterized by large exome-sequencing studies, however many tumors no in protein-coding genes. Non-coding are thought explain these cases, few non-coding drivers besides TERT promoter known. To fill this gap, we analyzed 150,000 cis -regulatory regions 1,844 whole cancer genomes from ICGC-TCGA...
Abstract There are limited data regarding the combined value of pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed retrospective analysis to assess prognostic role DS NHL who underwent salvage chemotherapy autologous stem cell transplantation (ASCT). identified 174 eligible between January 2013 March 2019. In multivariable analysis, DS, B symptoms,...
Robotic assistance recently gains increasing popularity in spinal surgery. provides higher effectiveness and safety especially complex anatomy environment. 16 patients with degenerative disc disease were operated robotic device («SpineAssist»; MAZOR Surgical Technologies, Caesarea, Israel). The robot was used for automated intraoperative positioning of the instruments according to preoperatively planned trajectories. enabled optimal screw placement even anatomical cases (thin pedicles...
<div>Abstract<p>Glioblastoma is the most common primary brain tumor in adults. While introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid recurrence remains universal. The transcriptional regulatory protein, inhibitor DNA-binding-1 (ID1), a key regulator cell phenotype cancer. We show that CRISPR-mediated knockout ID1 glioblastoma cells, breast adenocarcinoma melanoma cells dramatically reduced progression all three cancer...