Topology-Free Querying of Protein Interaction Networks

In the network querying problem, one is given a protein complex or pathway of species A and a protein-protein interaction network of species B; the goal is to identify subnetworks of B that are similar to the query in terms of sequence, topology, or both. Existing approaches mostly depend on knowledge of the interaction topology of the query in the network of species A; however, in practice, this topology is often not known. To address this problem, we develop a topology-free querying algorithm, which we call Torque. Given a query, represented as a set of proteins, Torque seeks a matching set of proteins that are sequence-similar to the query proteins and span a connected region of the network, while allowing both insertions and deletions. The algorithm uses alternatively dynamic programming and integer linear programming for the search task. We test Torque with queries from yeast, fly, and human, where we compare it to the QNet topology-based approach, and with queries from less studied species, where only topology-free algorithms apply. Torque detects many more matches than QNet, while giving results that are highly functionally coherent.