Biology subjects

Ghaddar, B.

Publications and source records attributed to Ghaddar, B..

4 recordsLinked to original sources

bioRxiv2022

Census: accurate, automated, deep, fast, and hierarchical scRNA-seq cell-type annotation

We developed Census, an automated, hierarchical cell-type identification method for scRNA-seq data that can deeply annotate normal cells in mammalian tissues and identify malignant cells and their likely cell of origin. When benchmarked on 44 atlas-scale normal and cancer, human and mouse tissues, Census significantly outperforms state-of-the-art methods across multiple metrics. Census is a fast and fully automated method, although users can seamlessly train their own models for customized applications.

bioinformatics↗

bioRxiv2022

Denoising sparse microbial signals from single-cell sequencing of mammalian host tissues

We developed SAHMI, a computational resource to identify truly present microbial nucleic acids and filter contaminants and spurious false-positive taxonomic assignments from standard transcriptomic sequencing of mammalian tissues. In benchmark studies, SAHMI correctly identifies known microbial infections present in diverse tissues. The application of SAHMI to single-cell and spatial genomic data enables co-detection of somatic cells and microorganisms and joint analysis of host-microbiome ecosystems.

genomics↗

bioRxiv2022

Reconstructing physical cell interaction networks from single-cell data using Neighbor-seq

Cell-cell interactions are the fundamental building blocks of tissue organization and multicellular life. We developed Neighbor-seq, a method to identify and annotate the architecture of direct cell-cell interactions and relevant ligand-receptor signaling from the undissociated cell fractions in massively parallel single cell sequencing data. Neighbor-seq accurately identifies microanatomical features of diverse tissue types such as the small intestinal epithelium, terminal respiratory tract, and splenic white pulp. It also captures the differing topologies of cancer-immune-stromal cell communications in pancreatic and skin tumors, which are consistent with the patterns observed in spatial transcriptomic data. Neighbor-seq is fast and scalable. It draws inferences from routine single-cell data and does not require prior knowledge about sample cell-types or multiplets. Neighbor-seq provides a framework to study the organ-level cellular interactome in health and disease, bridging the gap between single-cell and spatial transcriptomics.

genomics↗

bioRxiv2020

A Novel Model of Pancreatic Cancer Dormancy Reveals Mechanistic Insights and a Dormancy Gene Signature with Human Relevance

Latent recurrences following curative-intent pancreatic cancer surgery is a major clinical problem thought to be due to the reactivation of dormant tumor cells that disseminate before the primary tumor has been removed. How dormancy is established and ultimately reversed to drive recurrence is poorly understood. Here we introduce a novel model of pancreatic cancer dormancy that mimics early and latent survival outcomes of resected patients. Using single-cell transcriptomics we compared primary, dormant, and reactivated tumor cells and found the primary and reactivated tumor cell transcriptomes clustered together with and away from the dormant tumor cells. Using a chromatin accessibility assay we found dormancy exhibits large scale changes in chromatin remodeling. Dormant tumor cells express cancer stem cell markers that are lost upon reactivation and are chemotherapy resistant. We identified a dormancy gene signature and investigated this in patients undergoing surgery for localized PC by isolating cells from the primary tumor and liver disseminated tumor cells (DTCs) for single-cell transcriptomics. We found the signature correlated with DTCs indicating that these cells are dormant at the time of surgery. The signature also identified CCL5 as a novel dormancy marker in PC. Mechanisms of PC dormancy include upregulation of the transcriptional repressor Dec2 which drives quiescence, monoallelic suppression of the mutant KRAS allele by DNA methylation, and immunoregulation. We conclude that PC dormancy is a highly plastic and heterogeneous cellular state governed by tumor cell autonomous and non-autonomous mechanisms. One Sentence SummaryA novel model of resectable pancreatic cancer reveals pancreatic cancer dormancy is characterized by significant cellular plasticity, heterogeneity and chromatin remodeling

cancer biology↗