Imperial College London
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DrVahidShahrezaei

Faculty of Natural Sciences, Department of Mathematics

Reader in Biomathematics
 
 
 
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Contact

 

+44 (0)20 7594 8516v.shahrezaei Website

 
 
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Location

 

301BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Archer:2016:10.1016/j.cels.2016.10.012,
author = {Archer, N and Walsh, MD and Shahrezaei, V and Hebenstreit, D},
doi = {10.1016/j.cels.2016.10.012},
journal = {Cell Systems},
pages = {467--479.E12},
title = {Modeling Enzyme Processivity Reveals that RNA-Seq Libraries Are Biased in Characteristic and Correctable Ways},
url = {http://dx.doi.org/10.1016/j.cels.2016.10.012},
volume = {3},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Experimental procedures for preparing RNA-seq and single-cell (sc) RNA-seq libraries are based on assumptions regarding their underlying enzymatic reactions. Here, we show that the fairness of these assumptions varies within libraries: coverage by sequencing reads along and between transcripts exhibits characteristic, protocol-dependent biases. To understand the mechanistic basis of this bias, we present an integrated modeling framework that infers the relationship between enzyme reactions during library preparation and the characteristic coverage patterns observed for different protocols. Analysis of new and existing (sc)RNA-seq data from six different library preparation protocols reveals that polymerase processivity is the mechanistic origin of coverage biases. We apply our framework to demonstrate that lowering incubation temperature increases processivity, yield, and (sc)RNA-seq sensitivity in all protocols. We also provide correction factors based on our model for increasing accuracy of transcript quantification in existing samples prepared at standard temperatures. In total, our findings improve our ability to accurately reflect in vivo transcript abundances in (sc)RNA-seq libraries.
AU  - Archer,N
AU  - Walsh,MD
AU  - Shahrezaei,V
AU  - Hebenstreit,D
DO  - 10.1016/j.cels.2016.10.012
EP  - 479
PY  - 2016///
SN  - 2405-4712
SP  - 467
TI  - Modeling Enzyme Processivity Reveals that RNA-Seq Libraries Are Biased in Characteristic and Correctable Ways
T2  - Cell Systems
UR  - http://dx.doi.org/10.1016/j.cels.2016.10.012
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395782200011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/49655
VL  - 3
ER  -
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