Exploring lateral genetic transfer among microbial genomes using TF-IDF.

Yingnan Cong,Mark A Ragan,Yao-Ban Chan

doi:10.1038/srep29319

Abstract

Many microbes can acquire genetic material from their environment and incorporate it into their genome, a process known as lateral genetic transfer (LGT). Computational approaches have been developed to detect genomic regions of lateral origin, but typically lack sensitivity, ability to distinguish donor from recipient, and scalability to very large datasets. To address these issues we have introduced an alignment-free method based on ideas from document analysis, term frequency-inverse document frequency (TF-IDF). Here we examine the performance of TF-IDF on three empirical datasets: 27 genomes of Escherichia coli and Shigella, 110 genomes of enteric bacteria, and 143 genomes across 12 bacterial and three archaeal phyla. We investigate the effect of k-mer size, gap size and delineation of groups on the inference of genomic regions of lateral origin, finding an interplay among these parameters and sequence divergence. Because TF-IDF identifies donor groups and delineates regions of lateral origin within recipient genomes, aggregating these regions by gene enables us to explore, for the first time, the mosaic nature of lateral genes including the multiplicity of biological sources, ancestry of transfer and over-writing by subsequent transfers. We carry out Gene Ontology enrichment tests to investigate which biological processes are potentially affected by LGT.

Highlights

Many microbes can acquire DNA from an exogenous source and maintain it for transmission to subsequent generations, either incorporated into the new host genome or stabilised on a plasmid or other extra-chromosomal element
We reported that term frequency-inverse document frequency (TF-IDF) performs well with a small empirical dataset even though our target group consisted of a single sequence, presumably reducing the influence of the IDF term
To investigate the performance of TF-IDF on empirical data, we compare the number of regions identified as of potential lateral origin (Fig. 1a,c,e) and the total length of these regions (Fig. 1b,d,f) as a function of k and G in our three datasets

Summary

Introduction

Many microbes can acquire DNA from an exogenous source (other microbes, or the environment) and maintain it for transmission to subsequent generations, either incorporated into the new host genome or stabilised on a plasmid or other extra-chromosomal element. Taking genes (gene families) as the units of analysis, these approaches delineate orthogroups, multiply align sets of sequences, infer gene trees and compare their topologies against that of a reference “species” tree; well-supported instances of topological incongruence are taken as prima facie instances of LGT14–16 Such workflows are computationally demanding, yet cannot identify recombination breakpoints in individual genomes, and often fail to resolve the direction of transfer. They can be accelerated by use of approximate methods, better matching of computational tasks to hardware, and parallelisation, but remain slow with large datasets[17] For these reasons there is much interest in approaches that avoid altogether the potentially NP-hard steps of multiple sequence alignment, tree inference and tree reconciliation, while keeping track of regions of each individual genome in a manner that is agnostic to the number, size and nature of units of transfer. The regions identified by TF-IDF as lateral matched closely with those inferred by a well-regarded method, ALFY30, while in addition we identified two regions not found using ALFY that include genes encoding transporters and regulators of multidrug resistance and pathogenicity[8]

Methods

Results

Conclusion