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Rational association of genes with traits using a genome-scale gene network for Arabidopsis thaliana

Abstract

We introduce a rational approach for associating genes with plant traits by combined use of a genome-scale functional network and targeted reverse genetic screening. We present a probabilistic network (AraNet) of functional associations among 19,647 (73%) genes of the reference flowering plant Arabidopsis thaliana. AraNet associations are predictive for diverse biological pathways, and outperform predictions derived only from literature-based protein interactions, achieving 21% precision for 55% of genes. AraNet prioritizes genes for limited-scale functional screening, resulting in a hit-rate tenfold greater than screens of random insertional mutants, when applied to early seedling development as a test case. By interrogating network neighborhoods, we identify AT1G80710 (now DROUGHT SENSITIVE 1; DRS1) and AT3G05090 (now LATERAL ROOT STIMULATOR 1; LRS1) as regulators of drought sensitivity and lateral root development, respectively. AraNet (http://www.functionalnet.org/aranet/) provides a resource for plant gene function identification and genetic dissection of plant traits.

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Figure 1: Construction, accuracy and coverage of AraNet, a functional gene network for Arabidopsis.
Figure 2: Predictive power of AraNet for conserved and plant-specific biological processes.
Figure 3: Validation of AraNet by independent data sets.
Figure 4: AraNet correctly associates genes with many processes unique to plants, nonetheless relying at least in part on data from animals and yeast, which contribute evidence for linkages among genes that are broadly conserved but whose roles in Arabidopsis are in plant-specific processes.
Figure 5: Discovery of seed (embryo) pigmentation defective genes predicted by AraNet guilt by association.
Figure 6: Discovery of regulators of drought sensitivity and lateral root development from previously uncharacterized genes using AraNet.

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Acknowledgements

We are grateful to M. Ahn, A. Noorani and V. Bakshi for technical assistance, J. Shin for assistance on AraNet web design, T. Nakagawa (Shimane University, Japan) for providing pGWB2, K. Barton for providing lab space and D. Meinke, M. Running, W. Briggs, Z. Wang and K. Dreher for helpful discussions. This work was supported by Carnegie Institution for Science (B.A., S.Y.R.), a grant from the National Science Foundation (MCB-0520140) to S.Y.R. and by the National Research Foundation of Korea (NRF) grant funded by the Korean government (no. 2009-0063342, 2009-0070968) and Yonsei University (no. 2008-7-0284, 2008-1-0018) to I.L. and from the National Science Foundation, National Institutes of Health, and Welch (F1515) and Packard Foundations to E.M.M.

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Correspondence to Insuk Lee, Edward M Marcotte or Seung Y Rhee.

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Lee, I., Ambaru, B., Thakkar, P. et al. Rational association of genes with traits using a genome-scale gene network for Arabidopsis thaliana. Nat Biotechnol 28, 149–156 (2010). https://doi.org/10.1038/nbt.1603

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