DeTiN: overcoming tumor-in-normal contamination

Amaro Taylor-Weiner; Chip Stewart; Thomas Giordano; Mendy Miller; Mara Rosenberg; Alyssa Macbeth; Niall Lennon; Esther Rheinbay; Dan-Avi Landau; Catherine J Wu; Gad Getz

doi:10.1038/s41592-018-0036-9

DeTiN: overcoming tumor-in-normal contamination

Nat Methods. 2018 Jul;15(7):531-534. doi: 10.1038/s41592-018-0036-9. Epub 2018 Jun 25.

Authors

Amaro Taylor-Weiner^{1

2}, Chip Stewart¹, Thomas Giordano³, Mendy Miller¹, Mara Rosenberg¹, Alyssa Macbeth¹, Niall Lennon¹, Esther Rheinbay¹, Dan-Avi Landau^{1

4

5

6}, Catherine J Wu^{1

7

8

9}, Gad Getz^{10

11

12

13}

Affiliations

¹ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
² Harvard University, Cambridge, MA, USA.
³ Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
⁵ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
⁶ New York Genome Center, New York, NY, USA.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁹ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁰ Broad Institute of Harvard and MIT, Cambridge, MA, USA. [email protected].
¹¹ Department of Pathology, Harvard Medical School, Boston, MA, USA. [email protected].
¹² Cancer Center, Massachusetts General Hospital, Boston, MA, USA. [email protected].
¹³ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. [email protected].

Abstract

Comparison of sequencing data from a tumor sample with data from a matched germline control is a key step for accurate detection of somatic mutations. Detection sensitivity for somatic variants is greatly reduced when the matched normal sample is contaminated with tumor cells. To overcome this limitation, we developed deTiN, a method that estimates the tumor-in-normal (TiN) contamination level and, in cases affected by contamination, improves sensitivity by reclassifying initially discarded variants as somatic.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Computer Simulation
High-Throughput Nucleotide Sequencing / methods*
Humans
Mutation
Neoplasms / diagnosis*
Neoplasms / genetics*
Sequence Analysis, DNA / methods*

Abstract

Publication types

MeSH terms

Grants and funding