Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 4,981

The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.

Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples

Open access
Cibulskis, Kristian, Lawrence, Michael S, Carter, Scott L, Sivachenko, Andrey, Jaffe, David, Sougnez, Carrie, Gabriel, Stacey, Meyerson, Matthew, Lander, Eric S, Getz, Gad·2013·Nature Biotechnology
DOI 10.1038/nbt.2514
Open this paper in CoChat — free account

Abstract

Detection of somatic point substitutions is a key step in characterizing the cancer genome. However, existing methods typically miss low-allelic-fraction mutations that occur in only a subset of the sequenced cells owing to either tumor heterogeneity or contamination by normal cells. Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. We also describe benchmarking approaches that use real, rather than simulated, sequencing data to evaluate the sensitivity and specificity as a function of sequencing depth, base quality and allelic fraction. Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nbt.2514

Cites

17 of 17 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 29

  1. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011). · DOI · Paper page
  2. Banerji, S. et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486, 405–409 (2012). · DOI · Paper page
  3. Stransky, N. et al. The mutational landscape of head and neck squamous cell carcinoma. Science 333, 1157–1160 (2011). · DOI · Paper page
  4. Carter, S.L. et al. Absolute quantification of somatic DNA alterations in human cancer. Nat. Biotechnol. 30, 413–421 (2012). · DOI · Paper page
  5. Walter, M.J. et al. Clonal architecture of secondary acute myeloid leukemia. N. Engl. J. Med. 366, 1090–1098 (2012). · DOI · Paper page
  6. Park, S.Y., Gönen, M., Kim, H.J., Michor, F. & Polyak, K. Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J. Clin. Invest. 120, 636 (2010). · DOI · Paper page
  7. Navin, N. et al. Tumour evolution inferred by single-cell sequencing. Nature 472, 90–94 (2011). · DOI · Paper page
  8. Hou, Y. et al. Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell 148, 873–885 (2012). · DOI · Paper page
  9. Xu, X. et al. Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 148, 886–895 (2012). · DOI · Paper page
  10. Chapman, M.A. et al. Initial genome sequencing and analysis of multiple myeloma. Nature 471, 467–472 (2011). · DOI · Paper page
  11. Getz, G. et al. Comment on “The consensus coding sequences of human breast and colorectal cancers”. Science 317, 1500 (2007). · DOI
  12. Larson, D.E. et al. SomaticSniper: identification of somatic point mutations in whole genome sequencing data. Bioinformatics 28, 311–317 (2012). · DOI · Paper page
  13. Roth, A. et al. JointSNVMix: a probabilistic model for accurate detection of somatic mutations in normal/tumour paired next-generation sequencing data. Bioinformatics 28, 907–913 (2012). · DOI
  14. Saunders, C.T. et al. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics 28, 1811–1817 (2012). · DOI · Paper page
  15. Barbieri, C.E. et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat. Genet. 44, 685–689 (2012). · DOI · Paper page
  16. Bass, A.J. et al. Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A–TCF7L2 fusion. Nat. Genet. 43, 964–968 (2011). · DOI · Paper page
  17. Wang, L. et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N. Engl. J. Med. 365, 2497–2506 (2011). · DOI · Paper page
  18. Pugh, T.J. et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488, 106–110 (2012). · DOI · Paper page
  19. Berger, M.F. et al. The genomic complexity of primary human prostate cancer. Nature 470, 214–220 (2011). · DOI · Paper page
  20. Lohr, J.G. et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. USA 109, 3879–3884 (2012). · DOI · Paper page
  21. Wang, P. et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene advance, online publication, doi:10.1038/onc.2012.315 (23 July 2012). · DOI
  22. Durinck, S. et al. Temporal dissection of tumorigenesis in primary cancers. Cancer Discov. 1, 137–143 (2011). · DOI · Paper page
  23. Lee, R.S. et al. A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. J. Clin. Invest. 122, 2983–2988 (2012). · DOI · Paper page
  24. Forbes, S.A. et al. COSMIC: mining complete cancer genomes in the catalogue of somatic mutations in cancer. Nucleic Acids Res. 39, D945–D950 (2011). · DOI · Paper page
  25. DePristo, M.A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011). · DOI · Paper page
  26. Sherry, S.T. et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 29, 308–311 (2001). · DOI · Paper page
  27. Gnerre, S. et al. High-quality draft assemblies of mammalian genomes from massively parallel sequence data. Proc. Natl. Acad. Sci. USA 108, 1513–1518 (2011). · DOI · Paper page
  28. Shah, S.P. et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 461, 809–813 (2009). · DOI · Paper page
  29. Cibulskis, K. et al. ContEst: estimating cross-contamination of human samples in next-generation sequencing data. Bioinformatics 27, 2601–2602 (2011). · DOI · Paper page

Cited by

See all 4,981

Metadata

Authors
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D., Sougnez, C., Gabriel, S., Meyerson, M., Lander, E. S., & Getz, G.
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2013-02-10
Volume
31
Issue
3
Pages
213-219
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
DOI
10.1038/nbt.2514
OpenAlex
W1527347967
Cited by
4,981
References
17
FWCI
71.81
Type
journal article
Language
en
Open access
bronze
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.