Biology subjects

Nofech-Mozes, I.

Publications and source records attributed to Nofech-Mozes, I..

3 recordsLinked to original sources

bioRxiv2026

A Pan-Cancer Single-Cell Compendium of Intratumoural Heterogeneity.

Intratumoural heterogeneity remains one of the most formidable challenges in oncology, driving treatment resistance, disease progression, and poor patient outcomes. To uncover the cellular programs that define tumour composition and diversity, we interrogated over 3.6 million single cells derived from more than 1,000 primary and metastatic tumours spanning 14 diverse cancer types. Through the identification and quantification of coordinated gene expression programs, we delineated heterogeneous cancer cell states, exhibiting unique and clinically significant associations with patient survival. Integration with high-resolution spatial transcriptomics identified prognostic cancer cell states marked by aggressive transcriptional programs, co-localizing with invasive histological features and significantly enriched in metastatic settings. Functional drug perturbation screening uncovered drug vulnerabilities specific to distinct cancer cell states, supporting both direct targeting strategies and therapeutic reprogramming toward less aggressive cellular phenotypes. Collectively, this study offers novel insights into the relationship between intratumoural transcriptional heterogeneity, spatial organization, clinical outcomes, and therapeutic vulnerabilities.

cancer biology↗

bioRxiv2025

Blood-based Epigenetic Instability Linked to Human Aging and Disease

The abundance, dynamics, and context-dependent heterogeneity of DNA methylation--where a pattern considered abnormal in one cell type may be normal in another--poses challenges in identifying methylation abnormalities linked to disease risk. Through genome-wide analyses, we identified CpG sites with remarkably consistent methylation profiles in healthy whole blood, predominantly existing in an unmethylated state. We examined alterations at these epigenetically stable loci in diverse cohorts, including those with cardiovascular disease and hematological cancers. Our findings reveal methylation pattern disruption in myeloid and lymphoid malignancies, correlating with clonal burden fluctuations during leukemia treatment. In non-cancer cohorts, we observed that normally stable CpG sites exhibited progressive instability with advancing age, which was also associated with the onset of cardiovascular disease and decreased survival rates. This study links DNA methylation instability with the expansion of risk-prone blood cells and highlights its role as a biomarker for both cancer and cardiovascular disease.

genetics↗

bioRxiv2022

Pan-cancer classification of single cells in the tumour microenvironment

Single-cell RNA sequencing reveals valuable insights into cellular heterogeneity within tumour microenvironments (TMEs), paving the way for a deep understanding of cellular mechanisms contributing to cancer. However, high heterogeneity among the same cancer types and low transcriptomic variation in immune cell subsets present challenges for accurate, high-resolution confirmation of cells identities. Here we present scATOMIC; a modular annotation tool for malignant and non-malignant cells. We trained scATOMIC on >250,000 cancer, immune, and stromal cells defining a pan-cancer reference across 19 common cancer types and employed a novel hierarchical approach, outperforming current classification methods. We extensively confirmed scATOMICs accuracy on 198 tumour biopsies and 54 blood samples encompassing >420,000 cancer and a variety of TME cells. Lastly, we demonstrate scATOMICs practical significance to accurately subset breast cancers into clinically relevant subtypes and predict tumours primary origin across metastatic cancers. Our approach represents a broadly applicable strategy to analyze multicellular cancer TMEs.

bioinformatics↗