Getting started

Terminology and acronyms

Protein-Protein Interaction Network: List of protein-protein pairs that are known to interact in some fashion.
Multiple Network Alignment: Alignment of three or more PPINs.
Pairwise Network Alignment: Alignment of exactly two PPINs.
Node Alignment
Set of clusters consisting of proteins that are associated with one another by some means of network alignment.
Edge Alignment
Set of clusters consisting of induced edges (conserved interactions). Computed from a node alignment and the original PPINs.

Welcome to the SMAL web-server

The SMAL (Scaffold-Based Multiple Network Aligner) web-server is a public, open-source, web-based application for creating multiple network alignments (MNAs) from existing pairwise alignments (PNAs).
SMAL is particularly useful when multiple alignments relative to a particular PPIN of interest are required.
SMAL's key characteristics:

  • Any PNA algorithm can be used to create MNAs with SMAL.
  • Superior quality MNAs with regards to a desirable property can be created using SMAL by deploying a PNA algorithm that is optimized around said desirable property.
  • Creation of MNAs is very fast since SMAL complexity grows linearly with the number of aligned networks.
  • SMAL MNAs are persistent in that no information pertaining to the scaffold established in any of the incorporated PNAs is ever lost.
  • Iterative exploration of PPI data becomes much easier since SMAL MNAs can be enriched with additional PNAs.
  • SMAL is very permissive, creating alignments even if data is incomplete (i.e. SMAL tries to reconstruct missing data). SMAL then provides detailed ancillary information to help a scientist to judge and validate the alignment that has been obtained.
SMAL intuition


SMAL combines pairwise network alignments around a dedicated scaffold PPIN by associating all proteins aligned with the same scaffold protein. In the example, the triangle PPIN is selected as the scaffold, squares and circles are aligned pairwise with triangle and the two resulting PNAs ultimately combined. Induced edges are then computed based on the final MNA node-alignment and the interactions in the original PPINs.


4-species MNA around R. norvegicus

Left: Detailed zoom onto a highly conserved cluster.
Right: Snapshot of a large part of the network in a CoSE layout.

SMAL visualization screenshot SMAL visualization screenshot