MIA: Fabian Theis, Reconstructing trajectories and branching lineages in single cell genomics

Models, Inference and Algorithms
Broad Institute of MIT and Harvard
May 24, 2017

Fabian Theis
Helmholtz Zentrum München, TU Munich

Reconstructing trajectories and branching lineages in single cell genomics

Abstract: Single-cell technologies have gained popularity in developmental biology because they allow resolving potential heterogeneities due to asynchronicity of differentiating cells. Common data analysis encompasses normalization, followed by dimension reduction and clustering to identify subgroups. However, in the case of cellular differentiation, we may not expect clear clusters to be present - instead cells tend to follow continuous branching lineages.

In this talk I will first review methods for pseudotime ordering of cells according to their single cell profiles, which are used for reconstructing such trajectories. Then I will show that modeling the high-dimensional state space as a diffusion process, where cells move to close-by cells with a distance-dependent probability well reflects the differentiating characteristics. Based on the underlying diffusion map transition kernel, cells can be ordered according to a diffusion pseudotime (DPT), which allows for a robust identification of branching decisions and corresponding trajectories of single cells. After application to blood stem cell differentiation, I finish with current extensions towards single cell RNAseq time series and population models as well as driver-gene identification.

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