Project description:Tumors show substantial amounts of cellular heterogeneity by forming complex ecosystems of malignant and non-malignant cells. Herein, we present a comprehensive multi-omic cell atlas of matched single-cell transcriptome and single-cell chromatin accessibility profiles spanning over 150,000 cells from 11 human gynecologic tumors. By jointly analyzing these transcriptomic and chromatin accessibility profiles at single-cell resolution, we identify 115,734 total peak-to-gene links representing putative regulatory interactions. We find some of these regulatory interactions explain cell type-specific expression patterns of hallmark cancer pathway regulators such as the mTOR activator RHEB. We also leverage these data to infer differential transcription factor activity, such as ZEB1, across cell type-specific enhancers between two different fractions of the same patient tumor. Our work highlights the importance of precision medicine in the treatment of gynecologic cancers and we show that this resource will deepen our understanding of non-coding genomic regions in the context of tumor biology.
Project description:Deconvolution of regulatory mechanisms that drive transcriptional programs in cancer cells is key to understanding tumor biology. Herein, we present matched transcriptome (scRNA-seq) and chromatin accessibility (scATAC-seq) profiles at single-cell resolution from human ovarian and endometrial tumors processed immediately following surgical resection. This dataset reveals the complex cellular heterogeneity of these tumors and enabled us to quantitatively link variation in chromatin accessibility to gene expression. We show that malignant cells acquire previously unannotated regulatory elements to drive hallmark cancer pathways. Moreover, malignant cells from within the same patients show substantial variation in chromatin accessibility linked to transcriptional output, highlighting the importance of intratumoral heterogeneity. Finally, we infer the malignant cell type-specific activity of transcription factors. By defining the regulatory logic of cancer cells, this work reveals an important reliance on oncogenic regulatory elements and highlights the ability of matched scRNA-seq/scATAC-seq to uncover clinically relevant mechanisms of tumorigenesis in gynecologic cancers.
Project description:This study utilizes multi-omic biological data to perform deep immunophenotyping on the major immune cell classes in COVID-19 patients. 10X Genomics Chromium Single Cell Kits were used with Biolegend TotalSeq-C human antibodies to gather single-cell transcriptomic, surface protein, and TCR/BCR sequence information from 254 COVID-19 blood draws (a draw near diagnosis (-BL) and a draw a few days later (-AC)) and 16 healthy donors.