Response to “mass spectrometrists should search for all peptides, but assess only the ones they care about”

Access through your institution Buy or subscribe Noble and Keich reply: We find much to agree with in Sticker _et al_.1. Overall, it is clear that we are engaged in the same general project:

to first ensure the validity of our statistical confidence estimates and thereafter to maximize our statistical power in MS-based proteomics experiments. We also agree that controlling the

false discovery rate (FDR) among matches to a large peptide database and then reporting results relative to a selected subset of peptides does not correctly control the FDR. Indeed, this

point has been made previously on multiple occasions2,3 and is well established in the statistical literature4. We also agree that the 'sub-sub' strategy—searching a subset

database and evaluating the FDR within that subset—necessarily forces some matches between peptides in the subset and spectra that were generated by peptides outside of the database. This is

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Sticker, A., Martens, L. & Clement, L. _Nat. Methods_ 14,

643–644 (2017). Article  CAS  Google Scholar  * Baker, P.R., Medzihradszky, K.F. & Chalkley, R.J. _Mol. Cell. Proteomics_ 9, 1795–1803 (2010). Article  CAS  Google Scholar  * Fu, Y.

& Qian, X. _Mol. Cell. Proteomics_ 13, 1359–1368 (2014). Article  CAS  Google Scholar  * Efron, B. _Ann. Appl. Stat._ 2, 197–223 (2008). Article  Google Scholar  * Klimek, J. et al. _J.

Proteome Res._ 7, 96–103 (2008). Article  CAS  Google Scholar  * Engineer, C.B. et al. _Nature_ 513, 246–250 (2014). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This

work was supported by US National Institutes of Health awards R01 GM121818 and P41 GM103533 to W.S.N. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Genome Sciences, University

of Washington, Seattle, Washington, USA William Stafford Noble * Department of Computer Science and Engineering, University of Washington, Seattle, Washington, USA William Stafford Noble *

School of Mathematics and Statistics, University of Sydney, Sydney, New South Wales, Australia Uri Keich Authors * William Stafford Noble View author publications You can also search for

this author inPubMed Google Scholar * Uri Keich View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to William Stafford

Noble or Uri Keich. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Note

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Noble, W., Keich, U. Response to “Mass spectrometrists should search for all peptides, but assess only

the ones they care about”. _Nat Methods_ 14, 644 (2017). https://doi.org/10.1038/nmeth.4339 Download citation * Published: 29 June 2017 * Issue Date: 01 July 2017 * DOI:

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