Daily Archives: July 27, 2016

CellCODE: a robust latent variable approach to differential expression analysis for heterogeneous cell populations

Our next meeting will be at 12:30 on August 1st, in room 3160 of the Discovery building. Our Selected paper is CellCODE: a robust latent variable approach to differential expression analysis for heterogeneous cell populations.
The abstract is as follows.

Motivation: Identifying alterations in gene expression associated with different clinical states is important for the study of human biology. However, clinical samples used in gene expression studies are often derived from heterogeneous mixtures with variable cell-type composition, complicating statistical analysis. Considerable effort has been devoted to modeling sample heterogeneity, and presently, there are many methods that can estimate cell proportions or pure cell-type expression from mixture data. However, there is no method that comprehensively addresses mixture analysis in the context of differential expression without relying on additional proportion information, which can be inaccurate and is frequently unavailable.

Results: In this study, we consider a clinically relevant situation where neither accurate proportion estimates nor pure cell expression is of direct interest, but where we are rather interested in detecting and interpreting relevant differential expression in mixture samples. We develop a method, Cell-type COmputational Differential Estimation (CellCODE), that addresses the specific statistical question directly, without requiring a physical model for mixture components. Our approach is based on latent variable analysis and is computationally transparent; it requires no additional experimental data, yet outperforms existing methods that use independent proportion measurements. CellCODE has few parameters that are robust and easy to interpret. The method can be used to track changes in proportion, improve power to detect differential expression and assign the differentially expressed genes to the correct cell type. .

We welcome all who can join us for this discussion. Feel free to begin that discussion in the comments section below.