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. 2014 Nov 25;19(4):675–691. doi: 10.2478/s11658-014-0221-5

FunPred-1: Protein function prediction from a protein interaction network using neighborhood analysis

Sovan Saha 1, Piyali Chatterjee 2, Subhadip Basu 3,✉, Mahantapas Kundu 3, Mita Nasipuri 3
PMCID: PMC6275854  PMID: 25424913

Abstract

Proteins are responsible for all biological activities in living organisms. Thanks to genome sequencing projects, large amounts of DNA and protein sequence data are now available, but the biological functions of many proteins are still not annotated in most cases. The unknown function of such non-annotated proteins may be inferred or deduced from their neighbors in a protein interaction network. In this paper, we propose two new methods to predict protein functions based on network neighborhood properties. FunPred 1.1 uses a combination of three simple-yet-effective scoring techniques: the neighborhood ratio, the protein path connectivity and the relative functional similarity. FunPred 1.2 applies a heuristic approach using the edge clustering coefficient to reduce the search space by identifying densely connected neighborhood regions. The overall accuracy achieved in FunPred 1.2 over 8 functional groups involving hetero-interactions in 650 yeast proteins is around 87%, which is higher than the accuracy with FunPred 1.1. It is also higher than the accuracy of many of the state-of-the-art protein function prediction methods described in the literature. The test datasets and the complete source code of the developed software are now freely available at http://code.google.com/p/cmaterbioinfo/.

Keywords: Protein interaction network, Protein function prediction, Functional groups, Neighborhood analysis, Relative functional similarity, Edge clustering coefficient

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Abbreviations used

BIND

bimolecular interaction network database

DIP

Database of Interacting Proteins

ECC

edge clustering coefficient

HCS

highly connected subgraphs

LNPC

Laplacian network partitioning correlations

MCODE

molecular complex detection

MIPS

Munich Information Center for Protein Sequences

NMF

non-negative matrix factorization

PPI

protein-protein interactions

RNCS

restricted neighborhood search clustering algorithm

SVM

support vector machine

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