Estimating the size of the human interactome
- Michael P. H. Stumpf†,‡,§,
- Thomas Thorne†,
- Eric de Silva†,
- Ronald Stewart†,
- Hyeong Jun An¶,
- Michael Lappe¶, and
- Carsten Wiuf§,‖
- †Division of Molecular Biosciences, Imperial College London, Wolfson Building, London SW7 2AZ, United Kingdom;
- ‡Institute of Mathematical Sciences, Imperial College London, London SW7 2AZ, United Kingdom;
- ‖Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; and
- ¶Bioinformatics Research Center, University of Aarhus, 8000 Aarhus C, Denmark
-
Edited by Burton H. Singer, Princeton University, Princeton, NJ, and approved February 19, 2008 (received for review August 27, 2007)
Abstract
After the completion of the human and other genome projects it emerged that the number of genes in organisms as diverse as fruit flies, nematodes, and humans does not reflect our perception of their relative complexity. Here, we provide reliable evidence that the size of protein interaction networks in different organisms appears to correlate much better with their apparent biological complexity. We develop a stable and powerful, yet simple, statistical procedure to estimate the size of the whole network from subnet data. This approach is then applied to a range of eukaryotic organisms for which extensive protein interaction data have been collected and we estimate the number of interactions in humans to be ≈650,000. We find that the human interaction network is one order of magnitude bigger than the Drosophila melanogaster interactome and ≈3 times bigger than in Caenorhabditis elegans.
Footnotes
- §To whom correspondence may be addressed. E-mail: m.stumpf{at}imperial.ac.uk or wiuf{at}birc.au.dk
-
Author contributions: M.P.H.S., M.L., and C.W. designed research; M.P.H.S., T.T., E.d.S., M.L., and C.W. performed research; M.P.H.S., T.T., E.d.S., R.S., H.J.A., and C.W. analyzed data; and M.P.H.S., M.L., and C.W. wrote the paper.
-
The authors declare no conflict of interest.
-
This article is a PNAS Direct Submission.
-
See Commentary on page 6795.
-
This article contains supporting information online at www.pnas.org/cgi/content/full/0708078105/DCSupplemental.
-
↵ †† Eq. 8 is a general result for general (random) graphs; it is equally true for all ensembles of random graphs such as Erdös–Rényi and scale-free random graphs. In SI Text we further illustrate the simple quadratic relationship by using simulations.
-
↵ ‡‡ The degree–degree distribution is not significantly different from the product degree distribution (by using the Kolmogorov–Smirnov test); that is, P(k, l) ≈ P(k)P(l) for the datasets considered here.
- © 2008 by The National Academy of Sciences of the USA
