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SUMMARY:Single Cell Seminar: &quot\;&quot\;Distinct microbial and immune n
 iches of the human colon” + &quot\;Cardelino: Integrating whole exomes a
 nd single-cell transcriptomes to reveal phenotypic impact of somatic varia
 nts&quot\; -  Kylie James (Teichmann lab) + Raghd Rostom (Teichmann lab/St
 egle lab)
DTSTART:20190531T140000Z
DTEND:20190531T150000Z
UID:TALK125503@talks.cam.ac.uk
CONTACT:Lia Chappell
DESCRIPTION:Please come along the monthly genome campus Single Cell Semina
 r series. All are welcome\, including colleagues from Cambridge (though em
 ail me so we can book you in as a visitor with security). This month we ha
 ve two exciting talks\, please join us in C302 from 3.00 - 4.00pm on Frida
 y 31st May. \n\n\n1) Kylie James (Teichmann lab): "Distinct microbial and 
 immune niches of the human colon”\n\nGastrointestinal microbiota and imm
 une cells display regional specificity\, but associated changes of these c
 losely interacting communities along the colon are unknown. In this projec
 t\, I simultaneously assess microbiota and single immune cells across the 
 colon of disease-free humans\, with paired characterisation of immune cell
 s in the mesenteric lymph nodes\, to delineate colonic immune niches at st
 eady-state. I describe distinct T helper 1 cell activation and migration p
 rofiles 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 bac
 terial species.”\n\n\n2) Raghd Rostom (Teichmann lab/Stegle lab): "Carde
 lino: Integrating whole exomes and single-cell transcriptomes to reveal ph
 enotypic impact of somatic variants"\n\nDecoding the clonal substructures 
 of somatic tissues sheds light on cell growth\, development and differenti
 ation in health\, ageing and disease. DNA-sequencing\, either using bulk o
 r using single-cell assays\, has enabled the reconstruction of clonal tree
 s from frequency and co-occurrence patterns of somatic variants. However\,
  approaches to systematically characterize phenotypic and functional varia
 tions between individual clones are not established. Here we present carde
 lino (https://github.com/PMBio/cardelino)\, a computational method for inf
 erring the clonal tree configuration and the clone of origin of individual
  cells that have been assayed using single-cell RNA-seq (scRNA-seq). Carde
 lino allows effective integration of information from noisy clonal tree in
 ferences based on bulk exome-seq data\, and sparse variant alleles express
 ed in scRNA-seq data. After validating our model using simulations\, we ap
 ply cardelino to matched scRNA-seq and exome sequencing data from 32 human
  dermal fibroblast lines\, identifying hundreds of differentially expresse
 d genes between cells from different somatic clones. These genes are frequ
 ently enriched for cell cycle and proliferation pathways\, indicating a ke
 y role for cell division genes in non-neutral somatic evolution.
LOCATION:C302\, Sulston Building\, Wellcome Genome Campus\, Hinxton. CB10 
 1SA
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