Abstract
Motivation Intra-sample heterogeneity describes the phenomenon where a genomic sample contains a diverse set of genomic sequences. In practice, the true string sets in a sample are often unknown due to limitations in sequencing technology. In order to compare heterogeneous samples, genome graphs can be used to represent such sets of strings. However, a genome graph is generally able to represent a string set universe that contains multiple sets of strings in addition to the true string set. This difference between genome graphs and string sets is not well characterized. As a result, a distance metric between genome graphs may not match the distance between true string sets.
Results We extend a genome graph distance metric, Graph Traversal Edit Distance (GTED) proposed by Ebrahimpour Boroojeny et al., to FGTED to model the distance between heterogeneous string sets and show that GTED and FGTED always underestimate the Earth Mover’s Edit Distance (EMED) between string sets. We introduce the notion of string set universe diameter of a genome graph. Using the diameter, we are able to upper-bound the deviation of FGTED from EMED and to improve FGTED so that it reduces the average error in empirically estimating the similarity between true string sets. On simulated TCR sequences and Hepatitis B virus genomes, we show that the diameter-corrected FGTED reduces the average deviation of the estimated distance from the true string set distances by more than 250%.
Availability Data and source code for reproducing the experiments are available at: https://github.com/Kingsford-Group/gtedemedtest/
Contact carlk{at}cs.cmu.edu
Competing Interest Statement
This work was supported in part by the Gordon and Betty Moore Foundation's Data-Driven Discovery Initiative [GBMF4554 to C.K.], by the US National Institutes of Health [R01GM122935], the US NationalScience Foundation [DBI-1937540] and the Carnegie Mellon University School of Computer Science Sansom graduate fellowship for computational cancer research to Y.Q. C.K. is a co-founder of Ocean Genomics, Inc