ARTICLE Received 1 Nov 2012 | Accepted 4 Jul 2013 | Published 6 Aug 2013 Counting motifs in the human interactome Ngoc Hieu Tran 1 , Kwok Pui Choi 1,2 & Louxin Zhang 2,3 Small over-represented motifs in biological networks often form essential functional units of biological processes. A natural question is to gauge whether a motif occurs abundantly or rarely in a biological network. Here we develop an accurate method to estimate the occur- rences of a motif in the entire network from noisy and incomplete data, and apply it to eukaryotic interactomes and cell-specific transcription factor regulatory networks. The number of triangles in the human interactome is about 194 times that in the Saccharomyces cerevisiae interactome. A strong positive linear correlation exists between the numbers of occurrences of triad and quadriad motifs in human cell-specific transcription factor regulatory networks. Our findings show that the proposed method is general and powerful for counting motifs and can be applied to any network regardless of its topological structure. DOI: 10.1038/ncomms3241 OPEN 1 Department of Statistics and Applied Probability, National University of Singapore (NUS), Singapore 117546, Singapore. 2 Department of Mathematics, National University of Singapore (NUS), Singapore 119076, Singapore. 3 NUS Graduate School for Integrative Sciences and Engineering, Singapore 117456, Singapore. Correspondence and requests for materials should be addressed to L.X.Z. (email: matzlx@nus.edu.sg). NATURE COMMUNICATIONS | 4:2241 | DOI: 10.1038/ncomms3241 | www.nature.com/naturecommunications 1 & 2013 Macmillan Publishers Limited. All rights reserved.