Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign
| Autor: | Jong H. Park, Sisi Chen, Flavia Pichiorri, Tiffany Tsou, Matt Thomson, Paul Rivaud, Emeric J Charles, John R Haliburton |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Drug
Multidisciplinary Models Statistical Computer science Sequence Analysis RNA media_common.quotation_subject Lymphocyte Gene Expression Profiling Cell Probabilistic logic Computational Biology Gene Expression Disease Computational biology Biology Models Theoretical Biological Sciences Peripheral blood Heterogeneous population medicine.anatomical_structure Immune system medicine Humans Single-Cell Analysis media_common |
| Zdroj: | Proc Natl Acad Sci U S A |
| DOI: | 10.1101/421354 |
| Popis: | Single-cell measurement techniques can now probe gene expression in heterogeneous cell populations from the human body across a range of environmental and physiological conditions. However, new mathematical and computational methods are required to represent and analyze gene expression changes that occur in complex mixtures of single cells as they respond to signals, drugs, or disease states. Here, we introduce a mathematical modeling platform, PopAlign, that automatically identifies subpopulations of cells within a heterogeneous mixture, and tracks gene expression and cell abundance changes across subpopulations by constructing and comparing probabilistic models. Probabilistic models provide a low-error, compressed representation of single cell data that enables efficient large-scale computations. We apply PopAlign to analyze the impact of 40 different immunomodulatory compounds on a heterogeneous population of donor-derived human immune cells as well as patient-specific disease signatures in multiple myeloma. PopAlign scales to comparisons involving tens to hundreds of samples, enabling large-scale studies of natural and engineered cell populations as they respond to drugs, signals or physiological change. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|