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SUMMARY:Mapping tumor heterogeneity and developmental trajectories using 4
 0 markers at single cell resolution: - Dana Pe'er (Columbia University\, N
 YC)
DTSTART:20130429T150000Z
DTEND:20130429T160000Z
UID:TALK42951@talks.cam.ac.uk
CONTACT:Florian Markowetz
DESCRIPTION:It is now well appreciated that intra-tumor heterogeneity is o
 f critical importance.   There is remarkable molecular variability within 
 populations of tumor cells\, driven by both genetic and epigenetic variati
 on.  We address the challenge of identifying and characterizing tumor sub-
 populations through a combined experimental and computational approach.   
 We employ mass cytometry\, which accurately measures the expression and ph
 osphorylation states of more than forty proteins in thousands of single ce
 lls\, including surface proteins and signaling molecules.  The data is the
 n analyzed with our vi-SNE dimensionality reduction algoritm (based on t-S
 NE) that maps 40 dimensions down to two\, revealing the “shape” of the
  tumor and identifying subpopulations within. Application of vi-SNE to hea
 lthy immune-cells automatically separates cells based on their known immun
 e subtypes\, providing confidence in our approach. We applied our approach
  to Acute Myeloid Leukemia (AML) identifying distinct subpopulations that 
 differ in surface markers\, signaling and drug response. A striking signal
  in this data is dysregulated development trajectories in these cancers\, 
 hence we set to map normal development on healthy bone marrow\, where we c
 an observethe full gamut of developmental stages from progenitors to matur
 e B-cells. We developed a graph based trajectory algorithm (wanderlust) th
 at can trace a continuous progression from the hematopoietic stem cells\, 
 through the progenitor cells\, to the final\, committed B-cells.  Our deri
 ved map of healthy B-cell development revealed the order and timing of dev
 elopmental events at unprecedented resolution.  Both algorithmic details a
 nd biological findings will be discussed. 
LOCATION:Cancer Research UK Cambridge Research Institute\, Room 215
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