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Systematic identification of gene annotation errors in the widely used yeast mutation collections

Nature Methods volume 9, pages 373–378 (2012)Cite this article

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Abstract

The baker's yeast mutation collections are extensively used genetic resources that are the basis for many genome-wide screens and new technologies. Anecdotal evidence has previously pointed to the putative existence of a neighboring gene effect (NGE) in these collections. NGE occurs when the phenotype of a strain carrying a particular perturbed gene is due to the lack of proper function of its adjacent gene. Here we performed a large-scale study of NGEs, presenting a network-based algorithm for detecting NGEs and validating software predictions using complementation experiments. We applied our approach to four datasets uncovering a similar magnitude of NGE in each (7–15%). These results have important consequences for systems biology, as the mutation collections are extensively used in almost every aspect of the field, from genetic network analysis to functional gene annotation.

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Figure 1: Examples of the NIRVANA method.
Figure 2: Examples of NGEs predicted by NIRVANA, which we confirmed by complementation tests.
Figure 3: Examples of predicted non-NGE confirmed by complementation tests.
Figure 4: Validation of predicted NGE cases in the altered response to rapamycin network.

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Acknowledgements

We thank current and past members of the Sharan, Ruppin and Kupiec laboratories for helpful discussions, and D. Shore, R. Rolfes, B. Cairns, A. Johnson, S. Harashima, A.S. Bystrom, S. Moye-Rowley, M. Johnston, M.A. Clayton, G.H. Braus, B. Polevoda, R. Movva, E. Alani, J.P. Gélugne, V. Measday, D. Ramotar, A. Munn, E. Miller, B.C. Laurent, C. Brenner, M. Polymenis, J. Gerst, L. Aragon, D. Spatt, J. Boeke, G. Brown, C. Burd, M. Tamas, D.H. Wolf, Y. Hannun, Y. Ohsumi, Z. Ciesla, M. Choder, E. Bi, M. Bard, R. Schaffrath, H.U. Mosch, A. Amon, R. Parker, Y. Saeki, J. Kim, H.O. Park, E. Etsuchi, H. Nakatogana, B. Daignan-Fornier for providing plasmids. This work was supported by grants from the Israeli Ministry of Science and Technology and the Israel Cancer Foundation to M.K., and by a grant from the James McDonnel Fund to M.K., R.S. and E.R.; E.R. and R.S. were also supported by a Bikura grant from the Israel Science Foundation.

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Author notes

  1. Taly Ben-Shitrit and Nir Yosef: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel

    Taly Ben-Shitrit, Keren Shemesh & Martin Kupiec

  2. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA

    Nir Yosef

  3. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Nir Yosef

  4. School of Computer Science, Tel Aviv University, Ramat Aviv, Israel

    Roded Sharan & Eytan Ruppin

  5. Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel

    Eytan Ruppin

Authors
  1. Taly Ben-Shitrit
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  4. Roded Sharan
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  5. Eytan Ruppin
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Contributions

T.B.-S., N.Y., R.S., E.R. and M.K. conceived and designed the experiments and wrote the paper. T.B.-S. and K.S. carried out the wet laboratory experiments. N.Y. analyzed the data obtained. R.S. and E.R. contributed equally to this project.

Corresponding author

Correspondence to Martin Kupiec.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 2, 5 and 7–9 (PDF 874 kb)

Supplementary Table 1

NGE analysis of the TLM set. (XLS 107 kb)

Supplementary Table 3

Complexes that participate in the TLM and RR sets. (XLS 44 kb)

Supplementary Table 4

NGE analysis of the RR set. (XLS 102 kb)

Supplementary Table 6

Predicted and verified NGE in the TLM set. (XLS 37 kb)

Supplementary Software

NIRVANA software. (ZIP 2239 kb)

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Ben-Shitrit, T., Yosef, N., Shemesh, K. et al. Systematic identification of gene annotation errors in the widely used yeast mutation collections. Nat Methods 9, 373–378 (2012). https://doi.org/10.1038/nmeth.1890

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