Intrasample 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.
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 upperbound 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 Tcell receptor sequences and actual Hepatitis B virus genomes, we show that the diametercorrected FGTED reduces the average deviation of the estimated distance from the true string set distances by more than 250%.
Data and source code for reproducing the experiments are available at: https://github.com/KingsfordGroup/gtedemedtest/.
Supplementary data are available at Bioinformatics online.
 NSFPAR ID:
 10406907
 Publisher / Repository:
 Oxford University Press
 Date Published:
 Journal Name:
 Bioinformatics
 Volume:
 38
 Issue:
 Supplement_1
 ISSN:
 13674803
 Format(s):
 Medium: X Size: p. i404i412
 Size(s):
 p. i404i412
 Sponsoring Org:
 National Science Foundation
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