Enumerateblood – an R package to estimate the cellular composition of whole blood from Affymetrix Gene ST gene expression profiles

BMC Genomics

Methodology Article

Don D. Sin¹  J. Mark FitzGerald²  Mustafa Toma³  Robert Balshaw⁴  Casey P. Shannon⁵  Zsuzsanna Hollander⁵  Virginia Chen⁵  Raymond T. Ng⁶  Scott J. Tebbutt⁷  Bruce M. McManus⁸ 

[1] Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada;Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada;Institute for Heart and Lung Health, Vancouver, BC, Canada;Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada;Institute for Heart and Lung Health, Vancouver, BC, Canada;Division of Cardiology, University of British Columbia, Vancouver, BC, Canada;PROOF Centre of Excellence, Vancouver, BC, Canada;BC Centre for Disease Control, Vancouver, BC, Canada;PROOF Centre of Excellence, Vancouver, BC, Canada;Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada;PROOF Centre of Excellence, Vancouver, BC, Canada;Department of Computer Science, University of British Columbia, Vancouver, BC, Canada;Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada;Institute for Heart and Lung Health, Vancouver, BC, Canada;PROOF Centre of Excellence, Vancouver, BC, Canada;Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada;Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada;Institute for Heart and Lung Health, Vancouver, BC, Canada;PROOF Centre of Excellence, Vancouver, BC, Canada;Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada;Institute for Heart and Lung Health, Vancouver, BC, Canada;

关键词: Chronic Obstructive Pulmonary Disease;    Marker Gene;    Cellular Composition;    Reference Dataset;    Cell Proportion;   

DOI  :  10.1186/s12864-016-3460-1

 received in 2016-02-17, accepted in 2016-12-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMeasuring genome-wide changes in transcript abundance in circulating peripheral whole blood is a useful way to study disease pathobiology and may help elucidate the molecular mechanisms of disease, or discovery of useful disease biomarkers. The sensitivity and interpretability of analyses carried out in this complex tissue, however, are significantly affected by its dynamic cellular heterogeneity. It is therefore desirable to quantify this heterogeneity, either to account for it or to better model interactions that may be present between the abundance of certain transcripts, specific cell types and the indication under study. Accurate enumeration of the many component cell types that make up peripheral whole blood can further complicate the sample collection process, however, and result in additional costs. Many approaches have been developed to infer the composition of a sample from high-dimensional transcriptomic and, more recently, epigenetic data. These approaches rely on the availability of isolated expression profiles for the cell types to be enumerated. These profiles are platform-specific, suitable datasets are rare, and generating them is expensive. No such dataset exists on the Affymetrix Gene ST platform.ResultsWe present ‘Enumerateblood’, a freely-available and open source R package that exposes a multi-response Gaussian model capable of accurately predicting the composition of peripheral whole blood samples from Affymetrix Gene ST expression profiles, outperforming other current methods when applied to Gene ST data.Conclusions‘Enumerateblood’ significantly improves our ability to study disease pathobiology from whole blood gene expression assayed on the popular Affymetrix Gene ST platform by allowing a more complete study of the various components of this complex tissue without the need for additional data collection. Future use of the model may allow for novel insights to be generated from the ~400 Affymetrix Gene ST blood gene expression datasets currently available on the Gene Expression Omnibus (GEO) website.

【 授权许可】

CC BY   
© The Author(s). 2017