In single-cell sequencing analysis, several computational methods have been developed to map the cellular state space, but little has been done to map or create embeddings of the gene space. Here we formulate the gene embedding problem, design tasks with simulated single-cell data to evaluate representations, and establish ten relevant baselines. We then present a graph signal processing approach, called gene signal pattern analysis (GSPA), that learns rich gene representations from single-cell data using a dictionary of diffusion wavelets on the cell-cell graph.
View Article and Find Full Text PDFPancreatic endocrine-exocrine crosstalk plays a key role in normal physiology and disease. For instance, endocrine islet beta (β) cell secretion of insulin or cholecystokinin (CCK) promotes progression of pancreatic adenocarcinoma (PDAC), an exocrine cell-derived tumor. However, the cellular and molecular mechanisms that govern endocrine-exocrine signaling in tumorigenesis remain incompletely understood.
View Article and Find Full Text PDFStudies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adult reveals a continuous trajectory of epithelial cell states.
View Article and Find Full Text PDFThe peripheral T cell repertoire of healthy individuals contains self-reactive T cells. Checkpoint receptors such as PD-1 are thought to enable the induction of peripheral tolerance by deletion or anergy of self-reactive CD8 T cells. However, this model is challenged by the high frequency of immune-related adverse events in patients with cancer who have been treated with checkpoint inhibitors.
View Article and Find Full Text PDFSingle cell genomics has revolutionized our ability to map immune heterogeneity and responses. With the influx of large-scale data sets from diverse modalities, the resolution achieved has supported the long-held notion that immune cells are naturally organized into hierarchical relationships, characterized at multiple levels. Such a multigranular structure corresponds to key geometric and topological features.
View Article and Find Full Text PDFExciting advances in technologies to measure biological systems are currently at the forefront of research. The ability to gather data along an increasing number of omic dimensions has created a need for tools to analyze all of this information together, rather than siloing each technology into separate analysis pipelines. To advance this goal, we introduce a framework called the single-cell multi-modal generative adversarial network (scMMGAN) that integrates data from multiple modalities into a unified representation in the ambient data space for downstream analysis using a combination of adversarial learning and data geometry techniques.
View Article and Find Full Text PDFObjective The study aimed to evaluate the prevalence of oral leukoplakia and to assess the risk of developing oral leukoplakia in patients with tobacco-related habits among the populations of Chengalpattu district, Tamil Nadu, India. Materials and Methods Incidence and prevalence of oral leukoplakia differ among different populations in India due to cultural and demographic diversities. The results obtained from this study can be used as a reference in future research and policy-making for tobacco control.
View Article and Find Full Text PDF“Stem-like” TCF1 CD8 T (T) cells are necessary for long-term maintenance of T cell responses and the efficacy of immunotherapy, but, as tumors contain signals that should drive T cell terminal differentiation, how these cells are maintained in tumors remains unclear. In this study, we found that a small number of TCF1 tumor-specific CD8 T cells were present in lung tumors throughout their development. Yet, most intratumoral T cells differentiated as tumors progressed, corresponding with an immunologic shift in the tumor microenvironment (TME) from “hot” (T cell inflamed) to “cold” (non–T cell inflamed).
View Article and Find Full Text PDFis a useful model for intracellular parasitism given its ease of culture in the laboratory and genomic resources. However, as for many other eukaryotes, the genome contains hundreds of sequence gaps owing to repetitive and/or unclonable sequences that disrupt the assembly process. Here, we use the Oxford Nanopore Minion platform to generate near-complete de novo genome assemblies for multiple strains of and its near relative, We significantly improved genome contiguity (average N50 of ∼6.
View Article and Find Full Text PDFObjective: We sought to understand spatial-temporal factors and socioeconomic disparities that shaped U.S. residents' response to COVID-19 as it emerged.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2019
The positioning of chromosomes in the nucleus of a eukaryotic cell is highly organized and has a complex and dynamic relationship with gene expression. In the human malaria parasite , the clustering of a family of virulence genes correlates with their coordinated silencing and has a strong influence on the overall organization of the genome. To identify conserved and species-specific principles of genome organization, we performed Hi-C experiments and generated 3D genome models for five species and two related apicomplexan parasites.
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