Algorithms for matching partially labelled sequence graphs

Background

In order to find correlated pairs of positions between proteins, which are useful in predicting interactions, it is necessary to concatenate two large multiple sequence alignments such that the sequences that are joined together belong to those that interact in their species of origin. When each protein is unique then the species name is sufficient to guide this match, however, when there are multiple related sequences (paralogs) in each species then the pairing is more difficult. In bacteria a good guide can be gained from genome co-location as interacting proteins tend to be in a common operon but in eukaryotes this simple principle is not sufficient.

Results

The methods developed in this paper take sets of paralogs for different proteins found in the same species and make a pairing based on their evolutionary distance relative to a set of other proteins that are unique and so have a known relationship (singletons). The former constitute a set of unlabelled nodes in a graph while the latter are labelled. Two variants were tested, one based on a phylogenetic tree of the sequences (the topology-based method) and a simpler, faster variant based only on the inter-sequence distances (the distance-based method). Over a set of test proteins, both gave good results, with the topology method performing slightly better.

Conclusions

The methods develop here still need refinement and augmentation from constraints other than the sequence data alone, such as known interactions from annotation and databases, or non-trivial relationships in genome location. With the ever growing numbers of eukaryotic genomes, it is hoped that the methods described here will open a route to the use of these data equal to the current success attained with bacterial sequences.