Publications by authors named "C Smillie"
Article Synopsis
- Common genetic variation at the 11q23.1 locus is linked to colorectal cancer risk, complicating the understanding of its mechanisms due to complex gene interactions and expression patterns.
- The study utilizes various sequencing methods and mouse models to identify key genes, especially highlighting rs3087967 as a crucial variant that influences the expression of 21 genes associated with tuft cell markers.
- The findings suggest that the risk genotype at rs3087967 leads to a deficiency in tuft cells, which are important for tumor suppression, positioning these cells as protective elements in colorectal cancer development.
Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD.
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- - Antibody-secreting plasma cells (PCs) develop in secondary lymphoid organs but can also be found in various tissues throughout the body, each with unique functional adaptations based on their environment.
- - Surprisingly, all tissue-resident plasma cells (TrPCs) exhibit long lifespans, which is influenced by internal factors such as the type of immunoglobulin they produce.
- - The bone marrow serves as a unique reservoir for PCs from different origins, preserving features of their original tissue's transcriptional programming, highlighting how their longevity is shaped by both initial signals and their current tissue environment.
Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods.
View Article and Find Full Text PDFWe introduce BacDrop, a highly scalable technology for bacterial single-cell RNA sequencing that has overcome many challenges hindering the development of scRNA-seq in bacteria. BacDrop can be applied to thousands to millions of cells from both gram-negative and gram-positive species. It features universal ribosomal RNA depletion and combinatorial barcodes that enable multiplexing and massively parallel sequencing.
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