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Title: A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses

Abstract

Aneuploidy has been reported to occur at remarkably high levels in normal somatic tissues using Fluorescence In Situ Hybridization (FISH). Recently, these reports were contradicted by single-cell low-coverage whole genome sequencing (scL-WGS) analyses, which showed aneuploidy frequencies at least an order of magnitude lower. To explain these seemingly contradictory findings, we used both techniques to analyze artificially generated mock aneuploid cells and cells with natural random aneuploidy. Our data indicate that while FISH tended to over-report aneuploidies, a modified 2-probe approach can accurately detect low levels of aneuploidy. Further, scL-WGS tends to underestimate aneuploidy levels, especially in a polyploid background.

Authors:
 [1];  [2];  [3];  [3];  [1];  [1];  [1];  [4];  [1];  [5];  [6]
  1. Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Genetics
  2. Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Genetics; Rutgers Univ., New Brunswick, NJ (United States). Cancer Inst.
  3. Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Epidemiology and Population Health
  4. Buck Inst. for Research on Aging, Novato, California (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biosciences Division
  5. Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Epidemiology and Population Health; Univ. of Queensland, Brisbane (Australia). Inst. for Bioengineering and Nanotechnology
  6. Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Genetics, and Dept. of Pathology
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH)
OSTI Identifier:
1559238
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Andriani, Grasiella A., Maggi, Elaine, Piqué, Daniel, Zimmerman, Samuel E., Lee, Moonsook, Quispe-Tintaya, Wilber, Maslov, Alexander, Campisi, Judith, Vijg, Jan, Mar, Jessica C., and Montagna, Cristina. A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses. United States: N. p., 2019. Web. doi:10.1038/s41598-019-46606-w.
Andriani, Grasiella A., Maggi, Elaine, Piqué, Daniel, Zimmerman, Samuel E., Lee, Moonsook, Quispe-Tintaya, Wilber, Maslov, Alexander, Campisi, Judith, Vijg, Jan, Mar, Jessica C., & Montagna, Cristina. A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses. United States. doi:10.1038/s41598-019-46606-w.
Andriani, Grasiella A., Maggi, Elaine, Piqué, Daniel, Zimmerman, Samuel E., Lee, Moonsook, Quispe-Tintaya, Wilber, Maslov, Alexander, Campisi, Judith, Vijg, Jan, Mar, Jessica C., and Montagna, Cristina. Fri . "A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses". United States. doi:10.1038/s41598-019-46606-w. https://www.osti.gov/servlets/purl/1559238.
@article{osti_1559238,
title = {A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses},
author = {Andriani, Grasiella A. and Maggi, Elaine and Piqué, Daniel and Zimmerman, Samuel E. and Lee, Moonsook and Quispe-Tintaya, Wilber and Maslov, Alexander and Campisi, Judith and Vijg, Jan and Mar, Jessica C. and Montagna, Cristina},
abstractNote = {Aneuploidy has been reported to occur at remarkably high levels in normal somatic tissues using Fluorescence In Situ Hybridization (FISH). Recently, these reports were contradicted by single-cell low-coverage whole genome sequencing (scL-WGS) analyses, which showed aneuploidy frequencies at least an order of magnitude lower. To explain these seemingly contradictory findings, we used both techniques to analyze artificially generated mock aneuploid cells and cells with natural random aneuploidy. Our data indicate that while FISH tended to over-report aneuploidies, a modified 2-probe approach can accurately detect low levels of aneuploidy. Further, scL-WGS tends to underestimate aneuploidy levels, especially in a polyploid background.},
doi = {10.1038/s41598-019-46606-w},
journal = {Scientific Reports},
number = 1,
volume = 9,
place = {United States},
year = {2019},
month = {7}
}

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