Package 'SynMut'

Title: SynMut: Designing Synonymously Mutated Sequences with Different Genomic Signatures
Description: There are increasing demands on designing virus mutants with specific dinucleotide or codon composition. This tool can take both dinucleotide preference and/or codon usage bias into account while designing mutants. It is a powerful tool for in silico designs of DNA sequence mutants.
Authors: Haogao Gu [aut, cre], Leo L.M. Poon [led]
Maintainer: Haogao Gu <[email protected]>
License: GPL-2
Version: 1.21.0
Built: 2024-07-23 05:00:43 UTC
Source: https://github.com/bioc/SynMut

Help Index

Calculating the codon usage difference between sequences

Description

We use a least squares approach to estimate the codon usage difference between DNA sequences.

Usage

codon_dist(seq, ref)

## S4 method for signature 'ANY'
codon_dist(seq, ref)

Arguments

seq

the input DNA sequnece of DNAStringSet or regioned_dna class.
ref

the reference DNA sequnece of DNAStringSet or regioned_dna class.

Details

idea inspired by "Daniel Macedo de Melo Jorge, Ryan E. Mills, Adam S. Lauring, CodonShuffle: a tool for generating and analyzing synonymously mutated sequences, Virus Evolution, Volume 1, Issue 1, March 2015, vev012, https://doi.org/10.1093/ve/vev012"

Value

vector

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_cu(rgd.seq)

mut.seq <- codon_random(rgd.seq)
codon_dist(mut.seq, rgd.seq)
mut.seq2 <- codon_random(rgd.seq, keep = TRUE)
codon_dist(mut.seq2, rgd.seq)

Mimic a target codon usage bias

Description

Mutating the current DNA sequences in the regioned_dna object to mimic a target codon usage pattern.

Usage

codon_mimic(object, alt, numcode = 1, ...)

## S4 method for signature 'regioned_dna,vector'
codon_mimic(object, alt, numcode)

## S4 method for signature 'regioned_dna,DNAStringSet'
codon_mimic(object, alt, numcode)

## S4 method for signature 'DNAStringSet,DNAStringSet'
codon_mimic(object, alt, numcode)

Arguments

object

regioned_dna object
alt

target codon usage vector or DNAStringSet object representing target codon usage
numcode

The ncbi genetic code number for translation. Default value: 1. Details please refer to ?seqinr::translate ("https://rdrr.io/cran/seqinr/man/translate.html").
...

...

Details

The ideas for codon_mimic is similar to codon_to: first extract the mutable regions and then do the mutation. However the codons in the fixed (not mutable) regions will also alter the final codon usage, thus we have to adjust for the fixed codons when introducing sysnonymous codons. The ideal deisgn for codon_mimic is not unique as the swap between positions of the synonymous codons will not change the codon usage bias.

Details pleas refer to: https://koohoko.github.io/SynMut/algorithm.html

Value

regioned_dna

See Also

input_seq, codon_to, codon_random, dinu_to

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
target <- get_cu(rgd.seq)[2,]
new <- codon_mimic(rgd.seq, alt = target)
get_cu(new) - get_cu(rgd.seq)

target <- Biostrings::DNAStringSet("TTGAAAA-CTC-N--AAG")
new <- codon_mimic(rgd.seq, alt = target)
get_cu(new) - get_cu(rgd.seq)
get_freq(new) - get_freq(rgd.seq)
get_rscu(new) - get_rscu(rgd.seq)

Generate random synonymous mutations

Description

Generating random synonymous mutations (in user-defined region), with optionally keeping/not keeping the original codon usage bias.

Usage

codon_random(object, n = 1, keep = FALSE, numcode = 1, ...)

## S4 method for signature 'regioned_dna'
codon_random(object, n, keep, numcode)

## S4 method for signature 'DNAStringSet'
codon_random(object, n, keep, numcode)

Arguments

object

A regioned_dna object.
n

Optional n parameter specifying what proportion of the codons to be mutated. Default value: 1.
keep

Logical parameter controling whether keeping the codon usage bias
numcode

The ncbi genetic code number for translation. Default value: 1. Details please refer to ?seqinr::translate ("https://rdrr.io/cran/seqinr/man/translate.html").
...

...

Details

This method randomly sample synonymous codons for n propotion of every mutable codons in the sequences. This process will be likely to alter the codon usage bias of the original sequences. However the keep = TRUE argument help to preserve the codon usage bias. It is done via the synsequence function in seqinr package. The synsequence function essentially swaps the position of the synonymous codons without introducing new codons into the original sequences.

Value

A regioned_dna object containing the mutants; Or a DNAStringSet object if the input is a DNAStringSet object.

See Also

input_seq, dinu_to, codon_to, codon_mimic

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
set.seed(2019)
get_cu(codon_random(rgd.seq, n = 0.5))
get_cu(codon_random(rgd.seq))

Maximize or minimize the usage of certain codon.

Description

Input string of a codon to either the "max.codon = " or "min.codon = " parameter to maximize or minimize the usage of certain codon in the sequence.

Usage

codon_to(object, max.codon = NA, min.codon = NA, ...)

## S4 method for signature 'regioned_dna'
codon_to(object, max.codon, min.codon)

Arguments

object

A regioned_dna object.
max.codon

A string of a codon.
min.codon

A string of a codon.
...

...

Details

The ideas for this function is simple. We first extract the mutable regions for every sequences, then mutated the synonymous codons of the input to the desired. There will be only one ideal design for the maximization problem, however there may be numerous comparable designs having the same minimal usage of certain codon, as we randomly sample synonymous codon for substitution when solving the minimization problem.

Value

A regioned_dna object.

See Also

input_seq, dinu_to, codon_random, codon_mimic

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_cu(codon_to(rgd.seq, max.codon = "AAC")) - get_cu(rgd.seq)
get_cu(codon_to(rgd.seq, min.codon = "AAC")) - get_cu(rgd.seq)

Calculating the dinucleotide usage difference between sequences

Description

We use a least squares approach to estimate the dinucleotide usage difference between DNA sequences

Usage

dinu_dist(seq, ref)

## S4 method for signature 'ANY'
dinu_dist(seq, ref)

Arguments

seq

the input DNA sequnece of DNAStringSet or regioned_dna class.
ref

the reference DNA sequnece of DNAStringSet or regioned_dna class.

Details

similar method that applied in "Daniel Macedo de Melo Jorge, Ryan E. Mills, Adam S. Lauring, CodonShuffle: a tool for generating and analyzing synonymously mutated sequences, Virus Evolution, Volume 1, Issue 1, March 2015, vev012, https://doi.org/10.1093/ve/vev012"

Value

vector

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_cu(rgd.seq)

mut.seq <- codon_random(rgd.seq)
dinu_dist(mut.seq, rgd.seq)

Maximize or minimize the usage of certain dinucleotide.

Description

Input string of a dinucleotide to either the "max.dinu = " or "min.codon = " parameter to maximize or minimize the usage of certain codon in the sequence. Using a greedy algorithm with priority given to dinucleotide12 or dinucleotide23.

Usage

dinu_to(object, max.dinu = NA, min.dinu = NA, keep = FALSE, numcode = 1, ...)

## S4 method for signature 'regioned_dna'
dinu_to(object, max.dinu, min.dinu, keep, numcode)

Arguments

object

A regioned_dna object.
max.dinu

A string of a dinucleotide.
min.dinu

A string of a dinucleotide.
keep

A logical varibale stating if the codon usage of the original sequences should be keep. Default: False.
numcode

The ncbi genetic code number for translation. Default value: 1. Details please refer to ?seqinr::translate ("https://rdrr.io/cran/seqinr/man/translate.html").
...

...

Details

The detail strategy for this function please refer to: https://koohoko.github.io/SynMut/algorithm.html

Value

regioned_dna

See Also

input_seq, codon_to, codon_random, codon_mimic

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_du(dinu_to(rgd.seq, max.dinu = "cg")) - get_du(rgd.seq)
get_du(dinu_to(rgd.seq, min.dinu = "AA")) - get_du(rgd.seq)
get_du(dinu_to(rgd.seq, max.dinu = "cg", keep = TRUE)) - get_du(rgd.seq)
get_cu(dinu_to(rgd.seq, max.dinu = "CG", keep = TRUE)) - get_cu(rgd.seq)

Get codon usage matrix

Description

Access the codon usage matrix

Usage

get_cu(object, ...)

## S4 method for signature 'regioned_dna'
get_cu(object)

## S4 method for signature 'DNAStringSet'
get_cu(object)

Arguments

object

regioned_dna / DNAStringSet
...

...

Value

matrix

See Also

input_seq, get_region, get_nu, get_du, get_freq, get_rscu

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_cu(rgd.seq)

Get the DNAStringSet data

Description

Access the DNA sequence data in DNAStringSet.

Usage

get_dna(object, ...)

## S4 method for signature 'regioned_dna'
get_dna(object)

Arguments

object

A regioned_dna object.
...

...

Value

DNAStringSet

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_dna(rgd.seq)

Get dinucleotide usage matrix

Description

Access the dinucleotide usage matrix

Usage

get_du(object, ...)

## S4 method for signature 'regioned_dna'
get_du(object)

## S4 method for signature 'DNAStringSet'
get_du(object)

Arguments

object

regioned_dna / DNAStringSet
...

...

Value

matrix

See Also

input_seq, get_region, get_nu, get_cu, get_freq, get_rscu

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_du(rgd.seq)

Get codon usage frequency of synonymous codons

Description

Access the synonymous codon usage frequency

Usage

get_freq(object, numcode = 1, ...)

## S4 method for signature 'regioned_dna'
get_freq(object, numcode)

## S4 method for signature 'DNAStringSet'
get_freq(object, numcode)

## S4 method for signature 'matrix'
get_freq(object, numcode)

## S4 method for signature 'vector'
get_freq(object, numcode)

Arguments

object

regioned_dna / DNAStringSet / codon usage matrix (vector)
numcode

The ncbi genetic code number for translation. Default value: 1. Details please refer to ?seqinr::translate ("https://rdrr.io/cran/seqinr/man/translate.html").
...

...

Value

matrix

See Also

input_seq, get_region, get_cu, get_du, get_rscu

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_freq(rgd.seq)

Get nucleotide usage matrix

Description

Access the nucleotide usage matrix

Usage

get_nu(object, ...)

## S4 method for signature 'regioned_dna'
get_nu(object)

## S4 method for signature 'DNAStringSet'
get_nu(object)

Arguments

object

regioned_dna / DNAStringSet
...

...

Value

matrix

See Also

input_seq, get_region, get_cu, get_du, get_rscu

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_nu(rgd.seq)

Get the variable region

Description

Access the variable regions

Usage

get_region(object, ...)

## S4 method for signature 'regioned_dna'
get_region(object)

Arguments

object

regioned_dna
...

...

Value

list

See Also

input_seq, get_cu

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_region(rgd.seq)

Get Relative Synonymous Codon Usage (rscu) of synonymous codons

Description

Access the Relative Synonymous Codon Usage rscu

Usage

get_rscu(object, numcode = 1, ...)

## S4 method for signature 'regioned_dna'
get_rscu(object, numcode)

## S4 method for signature 'DNAStringSet'
get_rscu(object, numcode)

Arguments

object

regioned_dna / DNAStringSet / codon usage matrix (vector)
numcode

The ncbi genetic code number for translation. Default value: 1. Details please refer to ?seqinr::translate ("https://rdrr.io/cran/seqinr/man/translate.html").
...

...

Value

matrix

See Also

input_seq, get_region, get_cu, get_du, get_freq

Examples

filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)
get_rscu(rgd.seq)

Import region / constructing regioned_dna object

Description

Constructing regioned_dna from DNAStringSet. Optionally input a region data.frame to define restricted amino-acid region for mutation.

Usage

input_seq(object, region = NA, ...)

## S4 method for signature 'character'
input_seq(object, region)

## S4 method for signature 'DNAStringSet'
input_seq(object, region)

## S4 method for signature 'DNAString'
input_seq(object, region)

Arguments

object

Filepath or DNAstringSet. The input sequences is suggested to be in open reading frame(ORF).
region

NA. A data.frame specifying paticular regions (positions in amino acid sequence) that is allowed to be mutated in the sequences. Both 1 / 0 or TRUE / FALSE encoding is OK. Please refer to Examples below for reference.
...

...

Value

A regioned_dna-class object

See Also

get_cu, get_du, get_region, get_dna

Examples

# Creating a input_seq class directly from system file
filepath <- system.file("extdata", "example.fasta", package = "SynMut")
rgd.seq <- input_seq(filepath)

# Optionally input with region dataframe
filepath.fasta <- system.file("extdata", "example.fasta", package = "SynMut")
fp.csv <- system.file("extdata", "target_regions.csv", package = "SynMut")
region <- read.csv(fp.csv)
rgd.seq <- input_seq(filepath.fasta, region)

# Creating from exsisting DNAStringSet object
seq <- Biostrings::DNAStringSet("ATCGATCGA")
rgd.seq <- input_seq(seq)

An S4 class to record DNA sequences and variable regions for mutations

Description

Recording codon DNA sequences and region.

Slots

dnaseq

a DNAStingSet object recording the sequence(s)

region

a list specifying paticular regions in the sequences allowed to be mutated

Author(s)

Haogao Gu

See Also

input_seq, get_cu, get_region

Generate n random DNA sequnces of length m

Description

Generate n random DNA sequnces of length m, optional exclude stop codons.

Usage

seq_random(n = 1, m, no.stop.codon = FALSE, ...)

## S4 method for signature 'numeric,numeric'
seq_random(n, m, no.stop.codon)

Arguments

n

the number of the output sequence(s).
m

the length of the ouput sequence(s). Eighter a fixed number or a vector of different numbers.
no.stop.codon

Default FALSE. If TRUE, the stop codons in the frame 1 would be substituted to another random codon.
...

...

Value

a DNAStringSet object

Examples

seq_random(n = 1, m = 99)
seq_random(n = 10, m = 30)
seq_random(n = 10, m = 1:10)
seq.nsc <- seq_random(n = 10, m = 100, no.stop.codon = TRUE)
get_cu(seq.nsc)