Abstract
SummaryAnalysis of conservation of gene neighbourhoods over different evolutionary levels is important for understanding operon and gene cluster evolution, and predicting functional associations. Our tool FlaGs (standing for Flanking Genes) takes a list of NCBI protein accessions as input, clusters neighbourhood-encoded proteins into homologous groups using sensitive sequence searching, and outputs a graphical visualization of the gene neighbourhood and its conservation, along with a phylogenetic tree annotated with flanking gene conservation. FlaGs has demonstrated utility for molecular evolutionary analysis, having uncovered a new toxin–antitoxin system in prokaryotes and bacteriophages. The web tool version of FlaGs (webFlaGs) can optionally include a BLASTP search against a reduced RefSeq database to generate an input accession list and analyse neighbourhood conservation within the same run.Availability and implementationFlaGs can be downloaded from https://github.com/GCA-VH-lab/FlaGs or run online at http://www.webflags.se/.Supplementary information Supplementary data are available at Bioinformatics online.
Highlights
Conservation of gene order at long evolutionary distances is a strong indicator of a functional relationship among genes (Overbeek, et al, 1999)
While there are a range of tools that analyse gene neighbourhood conservation or integrate this data along with other metrics for functional association prediction, these tend to be either restrictive in the genomes that can be considered or require the creation of local genome databases (Garcia, et al, 2019; Lemoine, et al, 2008; Martinez-Guerrero, et al, 2008; Overmars, et al, 2013; Szklarczyk, et al, 2015)
Other tools that connect to the NCBI (National Center for Biotechnology Information; https://www.ncbi.nlm.nih.gov/) to detect operons may lack sensitive sequence searching for homology assignments of neighbourhood genes (Gumerov and Zhulin, 2020)
Summary
Conservation of gene order at long evolutionary distances is a strong indicator of a functional relationship among genes (Overbeek, et al, 1999). While there are a range of tools that analyse gene neighbourhood conservation or integrate this data along with other metrics for functional association prediction, these tend to be either restrictive in the genomes that can be considered (for example only complete genomes or those of model organisms) or require the creation of local genome databases (Garcia, et al, 2019; Lemoine, et al, 2008; Martinez-Guerrero, et al, 2008; Overmars, et al, 2013; Szklarczyk, et al, 2015).
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