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SUMMARY:Attempts at computational analysis of cell coordination at differe
 nt scales
DTSTART:20251104T153000
DTEND:20251104T163000
DTSTAMP:20260317T111441Z
UID:95f8622497f9ced0bd769e9b7206be42108119f08034f0e83a7d3fa2
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Peter Kharchenko\, Harvard Medical School\nCoordinated c
 ellular activity is fundamental to tissue function and is commonly perturb
 ed in disease\, yet scalable methods to quantify such coordination and its
  mechanisms remain limited. I will discuss these challenges and how my gro
 up has approached it at different scales: from analysis of population-scal
 e transcriptional analysis of patient cohorts\, down to local tissue conte
 xts resolved by spatial transcriptomics. First\, I will outline an interpr
 etable tensor‑decomposition framework that we designed for analysis of p
 opulation‑scale scRNA‑seq that captures multicellular expression progr
 ams - correlated state changes across cell types - and relates them to cli
 nical or environmental covariates in patient cohorts. We can use such mult
 icellular programs to look for factors potentially mediating this coordina
 tion and use genetic variation within population to evaluate causal hypoth
 esis. Though the mechanisms underlying such organism-wide coordination are
  also likely to be indirect. In contrast\, at the scale of small cellular 
 neighborhoods within tissues\, we expect more direct influences to be key.
  I will discuss how spatial transcriptomics can quantify coordination in s
 itu and the challenges faced by such approaches. In particular\, I will sh
 ow that most current techniques are vulnerable to pervasive segmentation e
 rrors that misattribute transcripts across adjacent cells\, generating spu
 rious region‑specific signals\, interaction‑changed genes\, and ligand
 –receptor pairs. I will describe a practical mitigation strategy based o
 n factorization of subcellular neighborhood composition vectors and probab
 ilistic labeling to identify and remove admixture‑driven factors\, there
 by restoring biologically coherent signals and improving interpretability 
 of downstream analyses. The seminar will thus connect global multicellular
  programs to spatially resolved mechanisms while delineating necessary con
 trols for confounding.
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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