README.md

In PhHermann/STRAH: Short Tandem Repeats Analysis of Hotspot Zones

STRAH

STRAH is an R package to search for short tandem repeats (STR) in a specified region of the (human) chromosome. This analysis can also be expanded when specifying that several chromosomes should be studied. These STRs can be grouped into hotspot as well as flanking regions of user specified length. Hotspots are defined by the double strand break maps from Pratto et al. (2014). Moreover, we implemented a function to search for a specified motif in a provided DNAStringSet-object, or a fasta-file, or a specified region of the (human) chromosome. For further details see the PDF Manual with complete documentation for each function. The accompanying paper with an application of STRAH can be found here.

Authors (Requests)

Please contact us in case of questions, comments, bug reports, etc...

Authors: Philipp Hermann, Monika Heinzl, Mehdin Masinovic, Angelika Heissl, Irene Tiemann-Boege, Andreas Futschik
E-Mail: [e-mail], [e-mail], [e-mail]

Dependencies & System Requirements

This package makes use of functions of other R-packages. Here we provide the list of the used R-packages:

• R (>= 2.10)
• Biostrings (>= 2.38.4)
• BSgenome.Hsapiens.UCSC.hg19

Notice that Biostrings and BSgenome.Hsapiens.UCSC.hg19 need to be installed via Biocondutor using the underlying links.

Installation

The ZIP-File of the package can be downloaded via "Clone or download" as well as the command line:

git clone https://github.com/PhHermann/STRAH.git
R CMD build STRAH
R CMD INSTALL STRAH_<version>.tar.gz

Using R one can also install the .tar.gz file with the following command:

install.packages("/PathToSTRAH/STRAH_<version>.tar.gz", repos=NULL, type="source")

Usage

STR_analysis

After loading the package in the workspace one can use the main function STR_analysis in order to analyse Short Tandem Repeats (STRs) in a given sequence of the (human) chromosome under study. This function calls STR_detection but we start with the description of STR_analysis and then explain further options with STR_detection.

require(STRAH)
STR_analysis(nr.STRs = 10, nr.mismatch = 0, chrs = "chr22", STR = "A", lens.grey = 0:5*1000,
  addToHs = 0, start.position = 30000000, end.position = 40000000, reverse.comp = FALSE, 
  bed_file = "", pos_matrix = "", output_file="")

Detailed descriptions of the main functions and all adjacent functions to detect and analyze STRs can be found via e.g.

?STRAH

The first two function arguments nr.STRs and nr.mismatch contain the minimum length of the short tandem repeat and the number of allowed mismatches per STR. Hence, both are non-negative integer parameters and we recommend to only search for STRs of at least length 6.

A string parameter chrs reflects the chromosome to be analyzed. This parameter should start with "chr" and is followed either by one of the intergers 1-22 or "X" or "Y". This parameter can also be a vector of several strings (or integers) to study several chromosomes.

A string parameter STR equals to one of the nucleotides A,C,G,T and by default one searches for poly-As (set to "A").

An integer parameter vector lens.grey contains the lengths of the regions to be analysed as outside regions next to the hotspot positions used. By default it is a vector of 6 integer values ending up with 5 regions of length 1kb, left and right from the hotspot regions.

An optional integer argument addToHs enables to enlarge the analyzed hotspot zones left and right by a positive integer value.

The two arguments start.position and end.position contain the corresponding positions on the chromosome and are indicated with positive integer values. Naturally, these positions must fit the start and end position of the given chromosome. If these are set to NA, then the function will analyze from the first position and until the last position of the chromosome. They can also be set separately to NA to search either from the starting position or until the end position if start.position or end.position are set to NA, respectively. If one wants to use several chromosomes with different start and end positions, we refer to the arguments bed_file or pos_matrix.

A logical parameter reverse.comp is by default FALSE, but if set to TRUE it enables to search for STRs on the reverse complement.

With the string parameter bed_file (leading to a prepared bed-file), STRAH reads the chromosome, start, and end position of the regions to be analyzed. These data can also be fed with the argument pos_matrix.

The parameter species enables to use other reference genomes than the human one installing for instance the chimpanzees reference genome BSgenome.Ptroglodytes.UCSC.panTro5 via e.g.:

source("http://bioconductor.org/biocLite.R")
biocLite("BSgenome.Ptroglodytes.UCSC.panTro5")
library(BSgenome.Ptroglodytes.UCSC.panTro5)

The string parameter dsb_map is set to the human DSB map of Pratto et al. (2014) by default. It can be changed to maps of different genomes. The DSB map for chimpanzees is included in the package which was tranlated via liftOver of the UCSC Genome Browser.

A user defined string output_file excluding the extension (always .bed) writes the output to this filename. By default it is an empty string and does not save an output file.

STR_detection

The function STR_detection detects short tandem repeats in any genome provided by the user. An example for the download of the chimpanzees reference genome can be found in the previous section. The following example shows how to detect STRs in the chimpanzees reference genome:

require(STRAH)
STR_detection(seqName = "", chrs = "chr1", start.position =222339618, end.position = 222339660,
 nr.STRs = 10, nr.mismatch = 0, reverse.comp = FALSE, STR = "A", species = BSgenome.Ptroglodytes.UCSC.panTro5)

The logical parameter translated_regions is FALSE by default. If set to TRUE then the function assumes that the parameters start.position and end.position were translated by some tool (e.g. liftOver) from one species to another. The untranslated and translated positions are included in the output.

Motif_detection

This function searches for a given "motif" in a sequence (seqName). The argument seqName can be either a DNAStringSet object or refers to a fasta-file. Additionally, we provide the option to specify a chromosome as well as start and stop position for a region of the human genome to be analyzed. Optionally, one can also specify the number of mismatches and whether the reverse complement has to be searched.

motif_detection(seqName = chr6_1580213_1582559, chrs="",
 start.position = NA, end.position = NA, motif = "CCNCCNTNNCCNC",
nr.mismatch = 1, reverse.comp = FALSE, print.status = TRUE)

motif_detection(seqName = "", chrs = "chr6", start.position = 1580213, end.position = 1582559,  motif = "CCNCCNTNNCCNC", nr.mismatch = 1, reverse.comp = FALSE, print.status = FALSE)

The following command detects the specified "motif" in the chimpanzees reference genome:

motif_detection(seqName = "", chrs = "chr1", start.position =222339618, end.position = 222339660, motif = "A", nr.mismatch = 0, reverse.comp = FALSE, print.status = FALSE, species = BSgenome.Ptroglodytes.UCSC.panTro5)

References

Heissl, A., Betancourt, A. J., Hermann, P., Povysil, G., Arbeithuber, B., Futschik, A., Ebner, T., Tiemann-Boege, I. (2018). Length asymmetry and heterozygosity strongly influences the evolution of poly-A microsatellites at meiotic recombination hotspots. bioRxiv 431841; doi.

Pratto, F., Brick, K., Khil, P., Smagulova, F., Petukhova, G. V. & Camerini-Otero, R. D. (2014) DNA recombination. Recombination initiation maps of individual human genomes. Science, 825 346, 1256442.

Kuhn RM, et al. (2013) The UCSC genome browser and associated tools, Brief. Bioinform., 14, 144-161.

PhHermann/STRAH documentation built on June 7, 2020, 6:15 p.m.