Package 'ModCon'

Title: Modifying splice site usage by changing the mRNP code, while maintaining the genetic code
Description: Collection of functions to calculate a nucleotide sequence surrounding for splice donors sites to either activate or repress donor usage. The proposed alternative nucleotide sequence encodes the same amino acid and could be applied e.g. in reporter systems to silence or activate cryptic splice donor sites.
Authors: Johannes Ptok [aut, cre]
Maintainer: Johannes Ptok <[email protected]>
License: GPL-3 + file LICENSE
Version: 1.15.0
Built: 2024-11-29 06:26:26 UTC
Source: https://github.com/bioc/ModCon

Help Index

Calculate HZEI integral of nucleotide sequence

Description

This function calcuales the HZEI integral of a nucleotide sequence.

Usage

calculateHZEIint(ntSequence)

Arguments

ntSequence

Character value of nucleotide sequence whose HZEI integral will be calculated. It should be at least 11 nt long and only contain bases 'A', 'G', 'C', 'T'.

Value

Integer value stating the HZEI integral of the given sequence ntSequence

Examples

## Example to increase HZEI integral for a given coding sequence
x <- calculateHZEIint('ATACCAGCCAGCTATTACATTT')

Calculate MaxEntScan score of a splice site sequence

Description

This function calculates the MaxEntScan score of either splice donor (SD) or acceptor sequences (SA).

Usage

calculateMaxEntScanScore(seqVector, ssType)

Arguments

seqVector

Character value of nucleotide sequence of a splice site sequence. SA sequences should be 23nt long (20 intronic, 3 exonic) and SD sequences should be 9nt long (3 exonic, 6 intronic). Only bases 'A', 'G', 'C', 'T' permitted.
ssType

Numeric value which indicates the type of splice site. Either '3' for an SA or '5' for an SD.

Value

Numeric vector stating the MaxEntScan score per splice site sequence entered with seqVector

Examples

calculateMaxEntScanScore('TTCCAAACGAACTTTTGTAGGGA',3)
calculateMaxEntScanScore('GAGGTAAGT',5)

CDS of firefly luciferase

Description

Character string of the nucleotide sequence encoding the firefly luciferase.

Usage

cds

Format

character string

Examples

cds

Adjust HZEI integral of nucleotide sequence

Description

Adjust the HZEI integral of a nucleotide sequence (min. 24nt long)

Usage

changeSequenceHZEI(inSeq, increaseHZEI=TRUE, nGenerations=50, parentSize=300,
startParentSize=1000, bestRate=50, semiLuckyRate=20, luckyRate=5, mutationRate=1e-04,
optiRate=100, sdMaximalHBS=10, acMaximalMaxent=4, nCores=-1)

Arguments

inSeq

Character value of nucleotide sequence (min 24nt long, only bases A, G, T or C)
increaseHZEI

Logical value if HZEI integral should be increased or decreased during SD degradation. If TRUE, function aims to increase HZEI integral.
nGenerations

Numeric value setting maximal number of generations
parentSize

Numeric value setting size of parent generations, generated from previous generations
startParentSize

Numeric value setting size of initiated parent generation of sequences
bestRate

Numeric value setting percentage how many of the fittest sequences are used to produce the next generation
semiLuckyRate

Numeric value setting percentage of sequences which are selected for breeding with a probability based on the respective HZEI-score integral
luckyRate

Numeric value setting percentage of sequences which are randomly selected for breeding
mutationRate

Numeric value setting chance of each codon, to mutate randomly within a child sequence
optiRate

Numeric value setting level of HZEI integral optimization
sdMaximalHBS

Numeric value of minimal HBS of SDs which should be tried to be degraded in their intrinsic strength
acMaximalMaxent

Numeric value of minimal MaxEntScan score of SAs which should be tried to be degraded in their intrinsic strength
nCores

Numeric value setting number of cores which should be used for parallel computations. If set to '-1' all availible cores are selected.

Value

Character value of a nucleotide sequence encoding the same amino acid sequence as inSeq, but an increased HZEI integral, due to alternative codon selection.

Examples

## Load R packages
library('parallel')
library('utils')
library('data.table')

## Set parameters for genetic algorithm
inSeq <- 'ATGGAAGACGCCAAAAACATAAAGAAAGGCCCGGCGCCATTCTATCCGCTGGAAGATGGAACC'

## Increase HZEI integral
res <- changeSequenceHZEI(inSeq)

## Setting additional parameters
res <- changeSequenceHZEI(inSeq, increaseHZEI=TRUE, nGenerations=50, parentSize=300,
startParentSize=1000, bestRate=50, semiLuckyRate=20, luckyRate=5, mutationRate=1e-04,
optiRate=100, sdMaximalHBS=10, acMaximalMaxent=4, nCores=1)

## Access sequence with highest generated HZEI intregral
res[[3]]

Table of codons and encoded amino acids

Description

Table of codons and encoded amino acids

Usage

Codons

Format

A data frame with columns:

ndiff

Indicator, how many codons encode the same amino acid

AA

Amino acid three-lettre code

name

Amino acid full name

seq

Codon sequence

Examples

Codons

Create codon matrix from coding nucleotide sequence

Description

This function creates a codon matrix with 2 rows and as many columns as codons within the sequence.

Usage

createCodonMatrix(cds)

Arguments

cds

Character value of nucleotide sequence whose HZEI integral will be calculated. It should be at least 3 nt long and only contain bases 'A', 'G', 'C', 'T'. Length must be a multiple of 3.

Value

Character matrix holding the encoded codon sequence in both rows.

Examples

## Example to create codon matrix
createCodonMatrix("ATGAATGATCAAAAGCTAGCC")

Generate new sequences by recombination

Description

This function generates new sequences from set of parental sequences through recombination.

Usage

createFilialSequencePopulation(sequenceVector, generateNrecombinedSequences)

Arguments

sequenceVector

Character vector of nucleotide sequences which will be used to create new sequences through recombination.
generateNrecombinedSequences

Numeric value setting number of recombined sequences which will be generated

Value

Character vector of nucleotide sequences, generated by recombination from the entered sequenceVector, holding as much filial sequences as stated in generateNrecombinedSequences. Modes of recombination are cross-over, insertion and random.

Examples

createFilialSequencePopulation(c('AAABBBCCCDDDEEEFFF','GGGHHHIIIJJJKKKLLL'), 3)

Remove or degrade intrinsic strength of specific GT site while keeping the HZEI integral neutral.

Description

Degrade or remove specific GT site from a coding sequence by codon selection keeping the HZEI integral near zero.

Usage

decreaseGTsiteStrength(cds, sdSeqStartPosition)

Arguments

cds

Character value of a coding nucleotide sequence which holds the splice site of interest. Sequence length must be devidable by 3 and only contain bases 'A', 'G', 'C', 'T'.
sdSeqStartPosition

Numeric value of position of the first nucleotide of the splice donor of interest

Value

Character vector of a nucleotide sequence encoding the same amino acid as the entered cds, but the intrinsic strength of a specific GT site within the CDS is degraded as much as possible.

Examples

library(data.table)
cds <- paste0('ATGGAAGACGCCAAAAACATAAAGAAAGGCCCGGCGCCATTCTATCCGCTGGAAGATGGAACCGCTGGAGAGCAACTGCA',

'TAAGGCTATGAAGAGATACGCCCTGGTTCCTGGAACAATTGCTTTTACAGATGCACATATCGAGGTGGACATCACTTACGCTGAGTACTTCGAAA',
'TGTCCGTTCGGTTGGCAGAAGCTATGAAACGATATGGGCTGAATACAAATCACAGAATCGTCGTATGCAGTGAAAACTCTCTTCAATTCTTTAT',
'GCCGGTGTTGGGCGCGTTATTTATCGGAGTTGCAGTTGCGCCCGCGAACGACATTTATAATGAACGTGAATTGCTCAACAGTATGGGCATTTCG',
'CAGCCTACCGTGGTGTTCGTTTCCAAAAAGGGGTTGCAAAAAATTTTGAACGTGCAAAAAAAGCTCCCAATCATCCAAAAAATTATTATCATGG',
'ATTCTAAAACGGATTACCAGGGATTTCAGTCGATGTACACGTTCGTCACATCTCATCTACCTCCCGGTTTTAATGAATACGATTTTGTGCCAGA',
'GTCCTTCGATAGGGACAAGACAATTGCACTGATCATGAACTCCTCTGGATCTACTGGTCTGCCTAAAGGTGTCGCTCTGCCTCATAGAACTGCC',
'TGCGTGAGATTCTCGCATGCCAGAGATCCTATTTTTGGCAATCAAATCATTCCGGATACTGCGATTTTAAGTGTTGTTCCATTCCATCACGGTT',
'TTGGAATGTTTACTACACTCGGATATTTGATATGTGGATTTCGAGTCGTCTTAATGTATAGATTTGAAGAAGAGCTGTTTCTGAGGAGCCTTCA',
'GGATTACAAGATTCAAAGTGCGCTGCTGGTGCCAACCCTATTCTCCTTCTTCGCCAAAAGCACTCTGATTGACAAATACGATTTATCTAATTTA',
'CACGAAATTGCTTCTGGTGGCGCTCCCCTCTCTAAGGAAGTCGGGGAAGCGGTTGCCAAGAGGTTCCATCTGCCAGGTATCAGGCAAGGATATG',
'GGCTCACTGAGACTACATCAGCTATTCTGATTACACCCGAGGGGGATGATAAACCGGGCGCGGTCGGTAAAGTTGTTCCATTTTTTGAAGCGAA',
'GGTTGTGGATCTGGATACCGGGAAAACGCTGGGCGTTAATCAAAGAGGCGAACTGTGTGTGAGAGGTCCTATGATTATGTCCGGTTATGTAAAC',
'AATCCGGAAGCGACCAACGCCTTGATTGACAAGGATGGATGGCTACATTCTGGAGACATAGCTTACTGGGACGAAGACGAACACTTCTTCATCG',
'TTGACCGCCTGAAGTCTCTGATTAAGTACAAAGGCTATCAGGTGGCTCCCGCTGAATTGGAATCCATCTTGCTCCAACACCCCAACATCTTCGA',
'CGCAGGTGTCGCAGGTCTTCCCGACGATGACGCCGGTGAACTTCCCGCCGCCGTTGTTGTTTTGGAGCACGGAAAGACGATGACGGAAAAAGAG',
'ATCGTGGATTACGTCGCCAGTCAAGTAACAACCGCGAAAAAGTTGCGCGGAGGAGTTGTGTTTGTGGACGAAGTACCGAAAGGTCTTACCGGAA',
'AACTCGACGCAAGAAAAATCAGAGAGATCCTCATAAAGGCCAAGAAGGGCGGAAAGATCGCCGTG')

sdSeqStartPosition <- 1001
cdsNew <- decreaseGTsiteStrength(cds, sdSeqStartPosition)
print(cdsNew)

Remove or degrade intrinisc strength of splice acceptors while adjusting HZEI integral.

Description

Degrade or remove splice acceptor sites of certain intrinsic strength (in MaxEntScan score) from a coding sequence by codon selection while keeping the HZEI integral up.

Usage

degradeSAs(fanFunc, maxhbs=10, maxME=4, increaseHZEI=TRUE)

Arguments

fanFunc

codon matrix with two rows (see example below)
maxhbs

Numeric treshold which strength of internal donor sites should be degraded (in HBS)
maxME

Numeric treshold which strength of internal acceptor sites should be degraded (in MaxEntScan score)
increaseHZEI

Logical value if HZEI integral should be increased or decreased during SD degradation. If TRUE, function aims to increase HZEI integral.

Value

Character value of a nucleotide sequence encoding the same amino acid as the entered codon matrix fan, but the intrinsic strength of all present splice acceptor (SA) sites is degraded as much as possible, in case they exceed the given treshold maxME. Additionally, splice donor site strengths greater maxhbs are avoided, during SA degradation.

Examples

library(data.table)
sdMaximalHBS <- 10
acMaximalMaxent <- 4
increaseHZEI <- TRUE
## Initiaing the Codons matrix plus corresponding amino acids
ntSequence <- 'TTTTGTCTTTTTCTGTGTGGCAGTGGGATTAGCCTCCTATCGATCTATGCGATA'
## Create Codon Matrix by splitting up the sequence by 3nt
fanFunc <- createCodonMatrix(ntSequence)
degradeSAs(fanFunc, maxhbs=sdMaximalHBS, maxME=acMaximalMaxent, increaseHZEI=increaseHZEI)

Remove or degrade intrinisc strength of splice donors while adjusting HZEI integral.

Description

Degrade or remove splice donor sites of certain intrinsic strength (in HBS) from a coding sequence by codon selection.

Usage

degradeSDs(fanFunc, maxhbs=10, increaseHZEI=TRUE)

Arguments

fanFunc

Codon matrix with two rows (see example below)
maxhbs

Numeric treshold which strength of internal donor sites should be degraded
increaseHZEI

Logical value of HZEI integral should be increased or decreased during SD degradation. If TRUE, function aims to increase HZEI integral.

Value

Character value of a nucleotide sequence encoding the same amino acid as the entered codon matrix fanFunc, but the intrinsic strength of all present splice donors (SD) sites is degraded as much as possible, in case they exceed the given treshold maxhbs.

Examples

library(data.table)
## Initiaing the Codons matrix plus corresponding amino acids
ntSequence <- 'TTTTCGATCGGGATTAGCCTCCAGGTAAGTATCTATCGATCTATGCGATAG'
## Create Codon Matrix by splitting up the sequence by 3nt
fanFunc <- createCodonMatrix(ntSequence)
degradeSDs(fanFunc, maxhbs=10, increaseHZEI=TRUE)

Randomly choose Codon to encode amino acid sequence

Description

Encode amino acid sequence by random codon selection

Usage

generateRandomCodonsPerAA(aaVector)

Arguments

aaVector

Character vector of amino acids in three lettre code (e.g. Met)

Value

Character value of a nucleotide sequence encoding the same amino acid as the entered by aaVector by random Codon selection.

Examples

generateRandomCodonsPerAA(c('Lys','Lys'))

Create overlapping subvectors

Description

Create overlapping subvectors from large vector

Usage

getOverlappingVectorsFromVector(largeVector, subvectorLength, subvectorOverlap )

Arguments

largeVector

Large character vector to break down into overlapping subvectors
subvectorLength

Numeric value of length of smaller subvectors
subvectorOverlap

Numeric value of length of subvector overlap

Value

Creates a list of overlapping subvectors from an input vector largeVector. The length of these overlapping subvectors is stated by subvectorLength and the overlap of the resulting subvectors is stated by subvectorOverlap.

Examples

getOverlappingVectorsFromVector(c(1,2,3,4), 2, 1)

Donor sequences and their HBS

Description

Donor sequences and their HBS

Usage

hbg

Format

A data frame with columns:

seq

11nt long donor sequence

hbs

HBS of the donor sequence

special_seq

Shorter version of the donor sequence

Examples

hbg

Hexamers and Z scores

Description

Hexamers and Z scores

Usage

hex

Format

A data frame with columns:

seq

Sequence of the hexamer.

value

ZEI-score of the hexamer from HEXplorer.

first

First codon within the hexamer.

second

Second codon within the hexamer.

first_AA

First encoded amino acid within the hexamer (three lettre code).

second_AA

Second encoded amino acid within the hexamer (three lettre code).

AA

Both encoded amino acid within the hexamer

Examples

hex

Increasing intrinsic strength of specific GT site while keeping the HZEI integral neutral.

Description

Increasing intrinsic strength specific GT site from a coding sequence by codon selection keeping the HZEI integral near zero.

Usage

increaseGTsiteStrength(cds, sdSeqStartPosition)

Arguments

cds

Coding nucleotide sequence which holds the splice site of interest
sdSeqStartPosition

Numeric value of position of the first nucleotide of the splice donor of interest

Value

Character vector of a nucleotide sequence encoding the same amino acid as the entered cds, but the intrinsic strength of a specific GT site within the CDS is enhanced as much as possible.

Examples

library(data.table)
cds <- paste0('ATGGAAGACGCCAAAAACATAAAGAAAGGCCCGGCGCCATTCTATCCGCTGGAAGATGGAACCGCTGGAGAGCAACTGCA',

'TAAGGCTATGAAGAGATACGCCCTGGTTCCTGGAACAATTGCTTTTACAGATGCACATATCGAGGTGGACATCACTTACGCTGAGTACTTCGAAA',
'TGTCCGTTCGGTTGGCAGAAGCTATGAAACGATATGGGCTGAATACAAATCACAGAATCGTCGTATGCAGTGAAAACTCTCTTCAATTCTTTAT',
'GCCGGTGTTGGGCGCGTTATTTATCGGAGTTGCAGTTGCGCCCGCGAACGACATTTATAATGAACGTGAATTGCTCAACAGTATGGGCATTTCG',
'CAGCCTACCGTGGTGTTCGTTTCCAAAAAGGGGTTGCAAAAAATTTTGAACGTGCAAAAAAAGCTCCCAATCATCCAAAAAATTATTATCATGG',
'ATTCTAAAACGGATTACCAGGGATTTCAGTCGATGTACACGTTCGTCACATCTCATCTACCTCCCGGTTTTAATGAATACGATTTTGTGCCAGA',
'GTCCTTCGATAGGGACAAGACAATTGCACTGATCATGAACTCCTCTGGATCTACTGGTCTGCCTAAAGGTGTCGCTCTGCCTCATAGAACTGCC',
'TGCGTGAGATTCTCGCATGCCAGAGATCCTATTTTTGGCAATCAAATCATTCCGGATACTGCGATTTTAAGTGTTGTTCCATTCCATCACGGTT',
'TTGGAATGTTTACTACACTCGGATATTTGATATGTGGATTTCGAGTCGTCTTAATGTATAGATTTGAAGAAGAGCTGTTTCTGAGGAGCCTTCA',
'GGATTACAAGATTCAAAGTGCGCTGCTGGTGCCAACCCTATTCTCCTTCTTCGCCAAAAGCACTCTGATTGACAAATACGATTTATCTAATTTA',
'CACGAAATTGCTTCTGGTGGCGCTCCCCTCTCTAAGGAAGTCGGGGAAGCGGTTGCCAAGAGGTTCCATCTGCCAGGTATCAGGCAAGGATATG',
'GGCTCACTGAGACTACATCAGCTATTCTGATTACACCCGAGGGGGATGATAAACCGGGCGCGGTCGGTAAAGTTGTTCCATTTTTTGAAGCGAA',
'GGTTGTGGATCTGGATACCGGGAAAACGCTGGGCGTTAATCAAAGAGGCGAACTGTGTGTGAGAGGTCCTATGATTATGTCCGGTTATGTAAAC',
'AATCCGGAAGCGACCAACGCCTTGATTGACAAGGATGGATGGCTACATTCTGGAGACATAGCTTACTGGGACGAAGACGAACACTTCTTCATCG',
'TTGACCGCCTGAAGTCTCTGATTAAGTACAAAGGCTATCAGGTGGCTCCCGCTGAATTGGAATCCATCTTGCTCCAACACCCCAACATCTTCGA',
'CGCAGGTGTCGCAGGTCTTCCCGACGATGACGCCGGTGAACTTCCCGCCGCCGTTGTTGTTTTGGAGCACGGAAAGACGATGACGGAAAAAGAG',
'ATCGTGGATTACGTCGCCAGTCAAGTAACAACCGCGAAAAAGTTGCGCGGAGGAGTTGTGTTTGTGGACGAAGTACCGAAAGGTCTTACCGGAA',
'AACTCGACGCAAGAAAAATCAGAGAGATCCTCATAAAGGCCAAGAAGGGCGGAAAGATCGCCGTG')

sdSeqStartPosition <- 1001
cdsNew <- increaseGTsiteStrength(cds, sdSeqStartPosition)
print(cdsNew)

ModCon

Description

Execute ModCon on a donor site within a coding sequnece either increasing or decreasing its HZEI weight.

Usage

ModCon(cds, sdSeqStartPosition, upChangeCodonsIn=16, downChangeCodonsIn=16,
optimizeContext=TRUE, sdMaximalHBS=10, acMaximalMaxent=4, optiRate=100,
nGenerations=50, parentSize=300, startParentSize=1000, bestRate=40,
semiLuckyRate=20, luckyRate=5, mutationRate=1e-04, nCores=-1)

Arguments

cds

Character value of coding nucleotide sequence which holds the splice site of interest
sdSeqStartPosition

Numeric value of the position of the first nucleotide of the splice donor of interest
upChangeCodonsIn

Numeric value of number of codons to change upstream of the donor site of interest
downChangeCodonsIn

Numeric value of number of codons to change downstream of the donor site of interest
optimizeContext

Character value which determines, if TRUE (the default) the donor context will be adjusted to increase the splice site HEXplorer weight (SSHW), if FALSE, the SSHW will be decreased.
sdMaximalHBS

Numeric value of minimal HBS of SDs which should be tried to be degraded in their intrinsic strength
acMaximalMaxent

Numeric value of minimal MaxEntScan score of SAs which should be tried to be degraded in their intrinsic strength
optiRate

Numeric value setting level of HZEI integral optimization
nGenerations

Numeric value setting maximal number of generations
parentSize

Numeric value setting size of parent generations, generated from previous generations
startParentSize

Numeric value setting size of initiated parent generation of sequences
bestRate

Numeric value setting percentage how many of the fittest sequences are used to produce the next generation
semiLuckyRate

Numeric value setting percentage of sequences which are selected for breeding with a probability based on the respective HZEI-score integral
luckyRate

Numeric value setting percentage of sequences which are randomly selected for breeding
mutationRate

Numeric value setting chance of each codon, to mutate randomly within a child sequence
nCores

Numeric value setting number of cores which should be used for parallel computations. If set to '-1' all availible cores are selected.

Value

Creates a character value of a coding nucleotide sequence encoding the same amino acid sequence as the entered cds, but with an alternative nucleotide surrounding around the splice donor (SD) sequence position, stated with sdSeqStartPosition. Depending on the entered optimizeContext, the SD surrounding is either adjusted aiming to enhance or decrease the splice site HEXplorer wheigth.

Examples

## Load R packages
library('parallel')
library('utils')
library('data.table')

## Set parameters for simplest use of ModCon (optimizing to 100%)
cds <- paste0('ATGGAAGACGCCAAAAACATAAAGAAAGGCCCGGCGCCATTCTATCCGCTGGAAGATGGAACCGCTGGAGAGCAACTGCA',

'TAAGGCTATGAAGAGATACGCCCTGGTTCCTGGAACAATTGCTTTTACAGATGCACATATCGAGGTGGACATCACTTACGCTGAGTACTTCGAAA',
'TGTCCGTTCGGTTGGCAGAAGCTATGAAACGATATGGGCTGAATACAAATCACAGAATCGTCGTATGCAGTGAAAACTCTCTTCAATTCTTTAT',
'GCCGGTGTTGGGCGCGTTATTTATCGGAGTTGCAGTTGCGCCCGCGAACGACATTTATAATGAACGTGAATTGCTCAACAGTATGGGCATTTCG',
'CAGCCTACCGTGGTGTTCGTTTCCAAAAAGGGGTTGCAAAAAATTTTGAACGTGCAAAAAAAGCTCCCAATCATCCAAAAAATTATTATCATGG',
'ATTCTAAAACGGATTACCAGGGATTTCAGTCGATGTACACGTTCGTCACATCTCATCTACCTCCCGGTTTTAATGAATACGATTTTGTGCCAGA',
'GTCCTTCGATAGGGACAAGACAATTGCACTGATCATGAACTCCTCTGGATCTACTGGTCTGCCTAAAGGTGTCGCTCTGCCTCATAGAACTGCC',
'TGCGTGAGATTCTCGCATGCCAGAGATCCTATTTTTGGCAATCAAATCATTCCGGATACTGCGATTTTAAGTGTTGTTCCATTCCATCACGGTT',
'TTGGAATGTTTACTACACTCGGATATTTGATATGTGGATTTCGAGTCGTCTTAATGTATAGATTTGAAGAAGAGCTGTTTCTGAGGAGCCTTCA',
'GGATTACAAGATTCAAAGTGCGCTGCTGGTGCCAACCCTATTCTCCTTCTTCGCCAAAAGCACTCTGATTGACAAATACGATTTATCTAATTTA',
'CACGAAATTGCTTCTGGTGGCGCTCCCCTCTCTAAGGAAGTCGGGGAAGCGGTTGCCAAGAGGTTCCATCTGCCAGGTATCAGGCAAGGATATG',
'GGCTCACTGAGACTACATCAGCTATTCTGATTACACCCGAGGGGGATGATAAACCGGGCGCGGTCGGTAAAGTTGTTCCATTTTTTGAAGCGAA',
'GGTTGTGGATCTGGATACCGGGAAAACGCTGGGCGTTAATCAAAGAGGCGAACTGTGTGTGAGAGGTCCTATGATTATGTCCGGTTATGTAAAC',
'AATCCGGAAGCGACCAACGCCTTGATTGACAAGGATGGATGGCTACATTCTGGAGACATAGCTTACTGGGACGAAGACGAACACTTCTTCATCG',
'TTGACCGCCTGAAGTCTCTGATTAAGTACAAAGGCTATCAGGTGGCTCCCGCTGAATTGGAATCCATCTTGCTCCAACACCCCAACATCTTCGA',
'CGCAGGTGTCGCAGGTCTTCCCGACGATGACGCCGGTGAACTTCCCGCCGCCGTTGTTGTTTTGGAGCACGGAAAGACGATGACGGAAAAAGAG',
'ATCGTGGATTACGTCGCCAGTCAAGTAACAACCGCGAAAAAGTTGCGCGGAGGAGTTGTGTTTGTGGACGAAGTACCGAAAGGTCTTACCGGAA',
'AACTCGACGCAAGAAAAATCAGAGAGATCCTCATAAAGGCCAAGAAGGGCGGAAAGATCGCCGTG')

## Execute ModCon
finalSequence <- ModCon(cds, 1001)

## Print final cds sequence with the alternative SD nucleotide surrounding
print(finalSequence)




## More parameters can be set for use of ModCon when not optimizing to 100% (e.g. 50%)

## Execute ModCon
finalSequence <- ModCon(cds, 1001, upChangeCodonsIn=16, downChangeCodonsIn=16,
optimizeContext=FALSE, sdMaximalHBS=10, acMaximalMaxent=4,
optiRate=50, nGenerations=5, parentSize=200, startParentSize=800,
bestRate=50, semiLuckyRate=10, luckyRate=5, mutationRate=1e-03, nCores=1)

## Print final cds sequence with the alternative SD nucleotide surrounding
print(finalSequence)

Randomly exchange codons within a set of sequences.

Description

For every codon within a set of nucleotide sequences randomly exchange the codon encoding the same amino acid to a certain chance.

Usage

mutatePopulation(sequenceVector, codonReplacementChance)

Arguments

sequenceVector

Character vector of nucleotide sequences (at least 3 nt long)
codonReplacementChance

Numeric value of chance of a codons within the sequences to get exchanged to another codon encoding the same amino acid

Value

Creates a character vector of coding nucleotide sequences encoding the same amino acid sequence as the entered sequenceVector. By a mutation rate stated in codonReplacementChance, codons are randomly exchanged, by alternative codons encoding the same amino acid.

Examples

mutatePopulation(c("CGCGATACGCTAAGCGCTACCGATAGTGGA","TGGGATATTTTAAGCGCTGACGATAGTGGA"), 0.1)

Generate new sequence from recombination of two sequences

Description

This function generates a new sequences through recombination of two parental sequences using 3 modi of recombination. Either random combination of codons, crossover recombination or insertion.

Usage

recombineTwoSequences(ntSequence1, ntSequence2, preferenceVector)

Arguments

ntSequence1

Character value of a nucleotide sequence
ntSequence2

Character value of a nucleotide sequence
preferenceVector

Numeric vector of length three which indicates which modus of recombination should be prefered. The first number states the chance of random recombination, the second number indicates the chance of cross-over recombination and the third number indicates the chance of insertion recombination.

Value

Character value of a nucleotide sequence, generated by recombination from the entered ntSequence1 and ntSequence2. Modes of recombination are cross-over, insertion and random and mode preferences can be stated by preferenceVector.

Examples

recombineTwoSequences("AGGGCCTGGAGGAGGCTT","TAAGGCAAGCCTGGACCC",c(1,3,2))

Select best HZEI and mean

Description

From all sequences of a generation report highest HZEI integral and mean HZEI integral of all.

Usage

selectBestAndMean(sequenceVector, clusterName, increaseHZEI=TRUE)

Arguments

sequenceVector

Character vector of nucleotide sequences
clusterName

Name of cluster generated with package parallel
increaseHZEI

Logical value if HZEI integral should be increased or decreased during SD degradation. If TRUE, function aims to increase HZEI integral.

Value

Numeric vector of length 2 stating the best HZEI integral and the mean HZEI integral of a nucleotide sequence vector sequenceVector. Depending on the increaseHZEI mode, the best HZEI integral value is either the highest (for increaseHZEI==TRUE) or lowest (for increaseHZEI==FALSE).

Examples

## Setup cluster
library(parallel)
nCores <- 1
clust <- makeCluster(nCores)
clusterExport(clust, list('getOverlappingVectorsFromVector', 'hex',
'calculateHZEIint'), envir = environment())
selectBestAndMean(c('CGCGATACGCTAAGCGCTACCGATAGTGGA','TGGGATATTTTAAGCGCTGACGATAGTGGA'),
clust, increaseHZEI=TRUE)

Selecting mating sequences from a pool of sequences

Description

Selecting sequences from a pool of nucleotide sequences based in chance and their HZEI integral.

Usage

selectMatingIndividuals(inputGeneration, whoMatesBestPercent=40, whoMatesSemiRandom=20,
whoMatesLuckily=5, clust, increaseHZEI=TRUE)

Arguments

inputGeneration

Character vector of nucleotide sequences
whoMatesBestPercent

Numeric value e.g. 20 (which would mean that sequences with the top 20 percent highest HZEI integral are selected for mating)
whoMatesSemiRandom

Numeric value (is always lower than total number of sequences in input_generation)
whoMatesLuckily

Numeric value (is always lower than total number of sequences in input_generation)
clust

Name of cluster generated with package parallel
increaseHZEI

Logical value of HZEI integral should be increased or decreased during SD degradation. If TRUE, function aims to increase HZEI integral.

Value

Character vector of nucleotide sequences which are selected from an entered vector of nucleotide sequences inputGeneration for creation of filial sequences by recombination. Sequences are selected by different criteria stated by whoMatesBestPercent, whoMatesSemiRandom, whoMatesLuckily and increaseHZEI.

Examples

## Setup cluster
library(parallel)
nCores <- 1
clust <- makeCluster(nCores)
clusterExport(clust, list('getOverlappingVectorsFromVector',
'hex'), envir=environment())
selectMatingIndividuals(c('CGCGATACGCGCGATACG','CGCGATACGTGGGATATT',
'CTAAGCGCTCGCGATACG','CGCGATACGTTAAGCGCT','GACGATAGTCGCGATACG'),
 whoMatesBestPercent=40, whoMatesSemiRandom=1, whoMatesLuckily=1, clust, increaseHZEI=TRUE)

Quickly manipulate HZEI integral of nucleotide sequence

Description

Quickly manipulate HZEI integral of nucleotide sequence (min. 21nt long)

Usage

slidingWindowHZEImanipulation(inSeq, increaseHZEI=TRUE)

Arguments

inSeq

Character value of nucleotide sequence (min 21nt long, only bases 'A', 'G', 'T' or 'C')
increaseHZEI

Logical value if HZEI integral should be increased or decreased during SD degradation. If TRUE, function aims to increase HZEI integral.

Value

Character value of a nucleotide sequence encoding the same amino acid sequence as inSeq, but an increased HZEI integral, due to alternative codon selection, accomplished through sliding window optimization.

Examples

# Load R packages
library('parallel')
library('utils')
library('data.table')

# Set parameters for genetic algorithm
inSeq <- 'ATGGAAGACGCCAAAAACATAAAGAAAGGCAGGCTAAGCCTAGCTTGCCATTGCCCGGCGCCATTCTATCCGCTGGAAGATGGAATT'

maximizedHZEIseq <- slidingWindowHZEImanipulation(inSeq, increaseHZEI=TRUE)
minimizedHZEIseq <- slidingWindowHZEImanipulation(inSeq, increaseHZEI=FALSE)

#Access sequence with maximized HZEI intregral
maximizedHZEIseq

#Access sequence with minimized HZEI intregral
minimizedHZEIseq

Start GUI of VarCon.

Description

Start graphical user interface for the ModCon application.

Usage

startModConApp()

Value

Shiny app

Examples

startModConApp()