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Genome Med. 2018 Apr 19;10(1):31. doi: 10.1186/s13073-018-0541-6.

Enabling multiplexed testing of pooled donor cells through whole-genome sequencing.

Chan Y1,2, Chan YK3,4, Goodman DB3,4,5, Guo X3,4, Chavez A6, Lim ET3,4, Church GM7,8.

Author information

1
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA. ychan@genetics.med.harvard.edu.
2
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA. ychan@genetics.med.harvard.edu.
3
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
4
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
5
Harvard-MIT Health Sciences and Technology, Cambridge, MA, 02139, USA.
6
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
7
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA. gchurch@genetics.med.harvard.edu.
8
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA. gchurch@genetics.med.harvard.edu.

Abstract

We describe a method that enables the multiplex screening of a pool of many different donor cell lines. Our method accurately predicts each donor proportion from the pool without requiring the use of unique DNA barcodes as markers of donor identity. Instead, we take advantage of common single nucleotide polymorphisms, whole-genome sequencing, and an algorithm to calculate the proportions from the sequencing data. By testing using simulated and real data, we showed that our method robustly predicts the individual proportions from a mixed-pool of numerous donors, thus enabling the multiplexed testing of diverse donor cells en masse.More information is available at https://pgpresearch.med.harvard.edu/poolseq/.

KEYWORDS:

Barcode free method; Expectation maximization algorithm; Multiplexed testing; Next-generation sequencing; Personal Genome Project; Single nucleotide polymorphisms

PMID:
29673390
PMCID:
PMC5909281
DOI:
10.1186/s13073-018-0541-6
[Indexed for MEDLINE]
Free PMC Article

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