Abstract
Most protein PageRank studies do not use signal flow direction information in protein interactions because this information was not readily available in large protein databases until recently. Therefore, four questions have yet to be answered: A) What is the general difference between signal emitting and receiving in a protein interactome? B) Which proteins are among the top ranked in directional ranking? C) Are high ranked proteins more evolutionarily conserved than low ranked ones? D) Do proteins with similar ranking tend to have similar subcellular locations? In this study, we address these questions using the forward, reverse, and non-directional PageRank approaches to rank an information-directional network of human proteins and study their evolutionary conservation. The forward ranking gives credit to information receivers, reverse ranking to information emitters, and non-directional ranking mainly to the number of interactions. The protein lists generated by the forward and non-directional rankings are highly correlated, but those by the reverse and non-directional rankings are not. The results suggest that the signal emitting/receiving system is characterized by key-emittings and relatively even receivings in the human protein interactome. Signaling pathway proteins are frequent in top ranked ones. Eight proteins are both informational top emitters and top receivers. Top ranked proteins, except a few species-related novel-function ones, are evolutionarily well conserved. Protein-subunit ranking position reflects subunit function. These results demonstrate the usefulness of different PageRank approaches in characterizing protein networks and provide insights to protein interaction in the cell.
Highlights
The Google PageRank algorithm [1] provides high-quality search result rankings for websites [1] and journals [2]
The ranking order of the 2,249 human proteins is listed in File S1, File S2, and File S3, for forward ranking, reverse ranking, and nondirectional ranking, respectively
The ranking order of the 379 feed-back pathway proteins is listed in File S4, File S5, and File S6, for forward ranking, reverse ranking, and non-directional ranking, respectively
Summary
The Google PageRank algorithm [1] provides high-quality search result rankings for websites [1] and journals [2]. A large information-directional network of more than 2,000 human proteins as well as a database of more than 300 feedback-like pathway proteins were developed using protein interaction directional scores (PIDS) to predict the protein interaction direction of signal flow and pathways [13]. A positive PIDS for protein A to protein B in a signaling pathway means that the informational interaction direction is from A to B. The PIDS approach is innovative and useful for predicting the interaction direction between two proteins in pathways within the network. Protein ranking may provide useful information complementing the PIDS values. The PIDS values and PageRank values for this large, information-directional human protein database may be a useful reference for studying proteins in other species
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