University of Cambridge > Talks.cam > Single Cell seminars at the Wellcome Genome Campus > Single Cell Seminar: ""Distinct microbial and immune niches of the human colon” + "Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants"

Single Cell Seminar: ""Distinct microbial and immune niches of the human colon” + "Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants"

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If you have a question about this talk, please contact Lia Chappell.

Location = Sanger Institute, CB10 1SA. Contact me for info on parking or minibus connections from Whittlesford Parkway train station.

Please come along the monthly genome campus Single Cell Seminar series. All are welcome, including colleagues from Cambridge (though email me so we can book you in as a visitor with security). This month we have two exciting talks, please join us in C302 from 3.00 – 4.00pm on Friday 31st May.

1) Kylie James (Teichmann lab): “Distinct microbial and immune niches of the human colon”

Gastrointestinal microbiota and immune cells display regional specificity, but associated changes of these closely interacting communities along the colon are unknown. In this project, I simultaneously assess microbiota and single immune cells across the colon of disease-free humans, with paired characterisation of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady-state. I describe distinct T helper 1 cell activation and migration profiles along the colon and characterise the transcriptional trajectory of T regulatory cells as they move from lymphoid organ to colon. Finally, I show a gradient of increasing B cell activation and clonality from caecum to sigmoid colon, and link this to the increasing number of reactive bacterial species.”

2) Raghd Rostom (Teichmann lab/Stegle lab): “Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants”

Decoding the clonal substructures of somatic tissues sheds light on cell growth, development and differentiation in health, ageing and disease. DNA -sequencing, either using bulk or using single-cell assays, has enabled the reconstruction of clonal trees from frequency and co-occurrence patterns of somatic variants. However, approaches to systematically characterize phenotypic and functional variations between individual clones are not established. Here we present cardelino (https://github.com/PMBio/cardelino), a computational method for inferring the clonal tree configuration and the clone of origin of individual cells that have been assayed using single-cell RNA -seq (scRNA-seq). Cardelino allows effective integration of information from noisy clonal tree inferences based on bulk exome-seq data, and sparse variant alleles expressed in scRNA-seq data. After validating our model using simulations, we apply cardelino to matched scRNA-seq and exome sequencing data from 32 human dermal fibroblast lines, identifying hundreds of differentially expressed genes between cells from different somatic clones. These genes are frequently enriched for cell cycle and proliferation pathways, indicating a key role for cell division genes in non-neutral somatic evolution.

This talk is part of the Single Cell seminars at the Wellcome Genome Campus series.

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