Alignment-free sequence comparison methods for phylogenetic analysis.
alfa (Alignment-free analysis) will be an R package for carrying out comparative genomic analysis using alignment-free methods. The tool relies on k-mer based methods and different metrics to compute the similarity/dissimilarity given a set of sequences. The result can then be plotted as a heatmap or used to construct phylogenetic trees.
While there has been numerous packages for alignment-free and phylogenetic analysis on R, none of the packages aim to integrate the workflow or provide a set of tools specifically tailored for phylogenetic analysis using alignment-free methods. Our package aim to simplify the workflow for performing phylogenetic analysis and in particular creation and evaluation of phylogenetic trees using alignment-free approaches. The results obtained from running the analyses using this package can be used for downstream analyses or for boostrapping in a more conventional phylogeny building workflow.
The package is developed using R version 4.1.2 (2021-11-01) on a device running x86_64-apple-darwin17.0 (macOS 12.6).
You can install the development version of alfa from GitHub with:
require("devtools")
devtools::install_github("gaojunxuan/alfa", build_vignettes = TRUE)
# intall Biostrings from Bioconductor
if (!require("BiocManager", quietly = TRUE))
install.packages("BiocManager")
BiocManager::install("Biostrings")
library("alfa")To run the shiny app
alfa::runAlfa()The package provides the following functions for analysis.
allKMers: extract all k-mers of the given stringcountVectors: create a count vector of k-mers in the two stringscreateDistanceMatrix: create a pairwise distance matrix for the given set of stringseuclideanDistnace: calculate the Euclidean distance between two strings using their count vectorsstandardizedEuclidean: calculate the standardized Euclidean distance between two strings using their count vectors, adjusted based on the overlapping capabilities of the k-mersneighborJoiningTree: construct and plot phylogenetic tree using neighbor-joiningupgmaTree: construct and plot phylogenetic tree using UPGMA
As well as the following functions for plotting and visualizing the results
neighborJoiningTree: construct and plot phylogenetic tree using neighbor-joiningupgmaTree: construct and plot phylogenetic tree using UPGMAplotPairwiseDist: plot pairwise distance matrix as a heatmapplotDistanceCorrelation: plot the pairwise distance in the distance matrix against the pairwise distance on the given phylogenetic tree
This package is developed by Kevin Gao. The idea of using count vectors for distance calculation is common for alignment-free analysis but the initial inspiration was from Zielezinski et al. The algorithm used for computing the standardized Euclidean distance was based on the paper A Measure of DNA Sequence Dissimilarity Based on Mahalanobis Distance between Frequencies of Words by Wu, Burke, and Davison. Moreover, various functions in this package including the tree constructing functions and plotting functions relied on ape by Paradis and Schliep. The package also uses functions from the stats package for computation.
Wu TJ, Burke JP, Davison DB. A measure of DNA sequence dissimilarity based on Mahalanobis distance between frequencies of words. Biometrics. 1997 Dec;53(4):1431-9.
Zielezinski, A., Vinga, S., Almeida, J. et al. Alignment-free sequence comparison: benefits, applications, and tools. Genome Biology. 2017; 18, 186.
Paradis E, Schliep K. "ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R." Bioinformatics. 2019; 35:526-528.
N Saitou, M Nei, The neighbor-joining method: a new method for reconstructing phylogenetic trees., Molecular Biology and Evolution. 1987 Jul; 4(4), 406--425.
R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.
H Wickham, J Hester, W Chang and J Bryan (2022). devtools: Tools to Make Developing R Packages Easier. R package version 2.4.5. https://CRAN.R-project.org/package=devtools
W Chang, J Cheng, JJ Allaire, C Sievert, B Schloerke, Y Xie, J Allen, J McPherson, A Dipert and B Borges (2022). shiny: Web Application Framework for R. R package version 1.7.2. https://CRAN.R-project.org/package=shiny
This package was developed as part of an assessment for 2022 BCB410H: Applied Bioinformat-
ics course at the University of Toronto, Toronto, CANADA. alfa welcomes issues,
enhancement requests, and other contributions. To submit an issue, use the GitHub issues.