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A Quantitative Comparison of Single-Cell Whole Genome
Amplification Methods
1. 1,2,4. 2,4. 2 1,2,3
Charles F. A. de Bourcy , Iwijn De Vlaminck , Jad N. Kanbar , Jianbin Wang , Charles Gawad ,
Stephen R. Quake1,2,4*
1 Department of Applied Physics, Stanford University, Stanford, California, United States of America, 2 Department of Bioengineering, Stanford University, Stanford,
California, United States of America, 3 Division of Hematology, Oncology, Stem Cell Transplantation and Cancer Biology, Department of Pediatrics, Stanford University
School of Medicine, Stanford, California, United States of America, 4 Howard Hughes Medical Institute, Stanford, California, United States of America
Abstract
Single-cell sequencing is emerging as an important tool for studies of genomic heterogeneity. Whole genome amplification
(WGA) is a key step in single-cell sequencing workflows and a multitude of methods have been introduced. Here, we
compare three state-of-the-art methods on both bulk and single-cell samples of E. coli DNA: Multiple Displacement
Amplification (MDA), Multiple Annealing and Looping Based Amplification Cycles (MALBAC), and the PicoPLEX single-cell
WGA kit (NEB-WGA). We considered the effects of reaction gain on coverage uniformity, error rates and the level of
background contamination. We compared the suitability of the different WGA methods for the detection of copy-number
variations, for the detection of single-nucleotide polymorphisms and for de-novo genome assembly. No single method
performed best across all criteria and significant differences in characteristics were obser
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