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SUMMARY:Single Cell Seminars (May): Unsupervised mapping for scRNA-seq\; J
 oint profiling of chromatin accessibility & more  - Vladimir Kiselev (Sang
 er)\, Stephen Clark (Babraham Institute)
DTSTART:20170526T140000Z
DTEND:20170526T150000Z
UID:TALK71884@talks.cam.ac.uk
CONTACT:Dr Lia Chappell
DESCRIPTION:\n_Note: Non-campus people should email LC5 @sanger.ac.uk so t
 hat you can be signed in as a visitor at reception. Please do this before 
 2.30pm on the day\, thanks!_\n\nPlease come along to the second of the reb
 ooted monthly campus Single Cell Seminar series. This month we have two ex
 citing talks\, one wet lab and one dry lab.\n\n*1) Vladimir Kiselev (Sange
 r): scmap - A tool for unsupervised mapping of single cell RNA-seq data to
  a reference database*\n\n*2) Stephen Clark (Babraham Institute: Joint pro
 filing of chromatin accessibility\, DNA methylation and transcription in s
 ingle cells*\n\n*Vlad's talk:* scRNA-seq allows for de novo identification
  of cell-types. There are currently plans for building a human cell atlas 
 that will serve as a reference for all of the cell types found in the huma
 n body. One of the most important uses of such an atlas will be for compar
 ison of new experiments - e.g. asking if the cells found in a disease samp
 le are present in the healthy reference. In addition to learning about whi
 ch known cell-type a given cell corresponds to\, a particularly important 
 question is whether or not a cell represents a new class which is not pres
 ent in the reference. I will present scmap - a tool for fast and accurate 
 projection of cells to a reference database for scRNA-seq data. We validat
 e scmap on several publicly available datasets collected from different pl
 atforms and labs. We also show that scmap is scalable and can be used with
  a reference database consisting of millions of cells.\n\n*Stephen's talk:
 * Technical advances enabling DNA accessibility measurements in single cel
 ls have characterised heterogeneity in a number of cell types but the tran
 scriptional consequences of this variability are unclear. We recently demo
 nstrated the utility of parallel single-cell sequencing to reveal novel li
 nks between epigenetic features\, such as DNA methylation\, and gene expre
 ssion. Here we build upon our method by introducing an in vitro GpC methyl
 ase step to mark regions of accessible chromatin prior to RNA capture and 
 bisulfite sequencing\; mapping genome-wide chromatin organisation\, endoge
 nous CpG methylation and transcription from the same single cell. Using si
 ngle-cell methylase accessibility\, we are able to profile a larger propor
 tion of the genome than published ATAC-seq and DNAse-seq methods. The abil
 ity to map closed chromatin (GpC unmethylated) as well as open chromatin (
 GpC methylated) increases confidence in the data and the presence of multi
 ple GpC sites within a given region gives sufficient resolution to discern
  nucleosome positions in single cells. We apply our method to pluripotent 
 mouse ES cells\, measuring heterogeneity in all three molecular layers whi
 ch we leverage to discover correlations and infer novel relationships\, re
 vealing strong and widespread associations between chromatin accessibility
  and DNA methylation.\n
LOCATION:C302\, Sulston Building\, Wellcome Genome Campus\, Hinxton. CB10 
 1SA
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