Abstract
Protein networks, describing physical interactions as well as functional associations between proteins, have been unravelled for many organisms in the recent past. Databases such as the STRING provide excellent resources for the analysis of such networks. In this contribution, we revisit the organisation of protein networks, particularly the centrality–lethality hypothesis, which hypothesises that nodes with higher centrality in a network are more likely to produce lethal phenotypes on removal, compared to nodes with lower centrality. We consider the protein networks of a diverse set of 20 organisms, with essentiality information available in the Database of Essential Genes and assess the relationship between centrality measures and lethality. For each of these organisms, we obtained networks of high-confidence interactions from the STRING database, and computed network parameters such as degree, betweenness centrality, closeness centrality and pairwise disconnectivity indices. We observe that the networks considered here are predominantly disassortative. Further, we observe that essential nodes in a network have a significantly higher average degree and betweenness centrality, compared to the network average. Most previous studies have evaluated the centrality–lethality hypothesis for Saccharomyces cerevisiae and Escherichia coli; we here observe that the centrality–lethality hypothesis hold goods for a large number of organisms, with certain limitations. Betweenness centrality may also be a useful measure to identify essential nodes, but measures like closeness centrality and pairwise disconnectivity are not significantly higher for essential nodes.
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Acknowledgments
Funding from IIT Madras and the seed grant BIO/12-13/579/NFSC/KARH is gratefully acknowledged. KR wishes to thank Dr. Saketha Nath (IIT Bombay) for several useful discussions.
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The authors declare that they have no conflict of interest.
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Nandita Damaraju and Govind Krishna Joshi have contributed equally to this article.
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11693_2013_9123_MOESM1_ESM.pdf
Supplementary material Variation in fraction of essential nodes, with increase in degree. The horizontal axis represents increasing node degrees, indicated as percentiles (x), while the vertical axis indicates the fraction of essential nodes in \(N_{x}^{d}\) , the set of nodes with degrees in the xth percentile and above. (PDF 38 kb)
11693_2013_9123_MOESM2_ESM.pdf
Supplementary material Variation in fraction of essential nodes, with increase in betweenness centrality. The horizontal axis represents increasing node betweenness centralities, indicated as percentiles (x), while the vertical axis indicates the fraction of essential nodes in \(N_{x}^{bc}\), the set of nodes with betweenness centralities in the xth percentile and above. (PDF 299 kb)
11693_2013_9123_MOESM3_ESM.pdf
Supplementary material Variation in fraction of essential nodes, with increase in closeness centrality. These plots are similar to those in Online Resources 1 and 2. (PDF 466 kb)
11693_2013_9123_MOESM4_ESM.pdf
Supplementary material Variation in fraction of essential nodes, with increase in pairwise disconnectivity index. These plots are similar to those in Online Resources 1 and 2. (PDF 26 kb)
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Raman, K., Damaraju, N. & Joshi, G.K. The organisational structure of protein networks: revisiting the centrality–lethality hypothesis. Syst Synth Biol 8, 73–81 (2014). https://doi.org/10.1007/s11693-013-9123-5
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DOI: https://doi.org/10.1007/s11693-013-9123-5