Data Exploration, Quality Control and Testing in Single-Cell qPCR-Based Gene Expression Experiments

Andrew McDavid; Greg Finak; Pratip K. Chattopadyay; Maria Dominguez; Laurie Lamoreaux; Steven S. Ma; Mario Roederer; Raphael Gottardo

arXiv · 1210.1226

Data Exploration, Quality Control and Testing in Single-Cell qPCR-Based Gene Expression Experiments

Andrew McDavid·Greg Finak·Pratip K. Chattopadyay·Maria Dominguez·Laurie Lamoreaux·Steven S. Ma·Mario Roederer·Raphael Gottardo

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Abstract

Cell populations are never truly homogeneous; individual cells exist in biochemical states that define functional differences between them. New technology based on microfluidic arrays combined with multiplexed quantitative polymerase chain reactions (qPCR) now enables high-throughput single-cell gene expression measurement, allowing assessment of cellular heterogeneity. However very little analytic tools have been developed specifically for the statistical and analytical challenges of single-cell qPCR data. We present a statistical framework for the exploration, quality control, and analysis of single-cell gene expression data from microfluidic arrays. We assess accuracy and within-sample heterogeneity of single-cell expression and develop quality control criteria to filter unreliable cell measurements. We propose a statistical model accounting for the fact that genes at the single-cell level can be on (and for which a continuous expression measure is recorded) or dichotomously off (and the recorded expression is zero). Based on this model, we derive a combined likelihood-ratio test for differential expression that incorporates both the discrete and continuous components. Using an experiment that examines treatment-specific changes in expression, we show that this combined test is more powerful than either the continuous or dichotomous component in isolation, or a t-test on the zero-inflated data. While developed for measurements from a specific platform (Fluidigm), these tools are generalizable to other multi-parametric measures over large numbers of events.

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Andrew McDavid, Greg Finak, Pratip K. Chattopadyay, Maria Dominguez, Laurie Lamoreaux, Steven S. Ma, Mario Roederer, Raphael Gottardo. 2012-10-03. Data Exploration, Quality Control and Testing in Single-Cell qPCR-Based Gene Expression Experiments. https://arxiv.org/abs/1210.1226

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