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Identification of transposable element insertion polymorphisms (TIPs) based on a pan-genome and large-scale resequencing data

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ITIPs: Identification of transposable element insertion polymorphisms (TIPs)

We developed a pipeline to identify population-scale TIPs based on a pan-genome analysis and large-scale resequencing of accessions in B. rapa. The pipeline for identifying population-scale TIPs employed three sequential steps: identification of insertions and deletions, construction of the TE insertion dataset, and determination of TIPs at a population scale.

Introduction

A pipeline developed to adequately retrieve population-scale TIPs

Step 1:Identification of insertions and deletions in the B. rapa pan-genome.

In this step, we used each of the 20 B. rapa genomes as the reference and identified insertions and deletions in the B. rapa pan-genome using the smartie-sv piepeline.

image

Step 2: Construction of the TE insertion dataset.

After obtaining insertions and deletions, we mapped each insertion or deletion onto the B. rapa TE library. If the similarity and coverage of one deletion (or insertion) were greater than 80% (also called ‘the 80-80 rule’), then the deletion (or insertion) was defined as a TE insertion. Furthermore, we proposed the concepts of ‘aligned regions’ and ‘unaligned regions’ to describe TIPs in the pan-genome. The concepts were based on Chiifu genomic sequences. If genomic sequences from the other 19 accessions could be covered by the Chiifu sequences, we denoted such regions as being ‘aligned regions’; if the genomic sequences in the other genomes could not be covered by the Chiifu sequences, we defined them as ‘unaligned regions’.

image

Step 3: Determination of TIPs at a population scale.

We implemented the strategy by mapping the short reads onto the TE insertion and their flanking sequences. If one or two boundaries for a TE insertion were covered by the short reads, we defined this accession as harboring the same TE insertion. The detailed process included three steps: we first extracted the flanking sequences of each TE insertion (including 1 kb upstream and downstream of the TE insertion); then, the upstream flanking sequence, the TE insertion sequence, and the downstream flanking sequence were linked together in order. After that, we mapped the population-scale resequencing short reads onto our constructed target sequences. If a read in one accession was directly aligned to the upstream and downstream flanking sequences, we considered that there was no TE insertion in this accession; if a read in one accession was directly aligned to the TE insertion sequence and at least one flanking sequence (upstream or downstream flanking sequence), then the accession was considered to harbor the same TE insertion.

image

Installation

The pipeline ITIPs is installation-free but requires dependencies: smartie-sv and bwa (Version: 0.7.17-r1188). The binary file of bwa have been provided in the /ITIPs/scripts/ folder.

git clone https://github.com/caixu0518/ITIPs.git
cd ITIPs
chmod u+x *pl 
cd scripts
chmod u+x *

Inputs

Two types of inputs are required for ITIPs

  1. Genome fasta. i.e. reference genome, query 1 genome, query 2 genome ......
  2. population-scale resequencing reads. i.e. Sam1_1.fq.gz, Sam1_2.fq.gz ......

Outputs

Phase 1: the pipeline will generated reference TE insertion and non-reference TE insertion. i.e. reference_TE.insertions.xls, non-reference_TE.insertions.xls

Chr     Start   End     Type    SVlen   Upstream        Downstream      Gene    CDS
A10     90093   90797   deletion        704     query1;query2   BraA10g000190.3.1C      BraA10g000200.3.1C      -       -
A10     158873  161879  deletion        3006    query1  BraA10g000350.3.1C      BraA10g000340.3.1C      -       -
A10     161994  162256  deletion        262     query1  BraA10g000350.3.1C      -       -       -
A10     248968  253788  deletion        4820    query2  -       BraA10g000500.3.1C      -       -
A10     252712  253372  deletion        660     query1  -       BraA10g000500.3.1C      -       -
A10     253389  254595  deletion        1206    query1  -       BraA10g000500.3.1C      -       -
A10     253794  254442  deletion        648     query2  -       BraA10g000500.3.1C      -       -
A10     325403  326892  deletion        1489    query1  BraA10g000690.3.1C      -       -       -
A10     325405  325631  deletion        226     query2  BraA10g000680.3.1C      -       -       -
A10     325635  326898  deletion        1263    query2  BraA10g000690.3.1C      -       -       -
A10     329657  332373  deletion        2716    query2  -       BraA10g000690.3.1C      -       -

Phase 2: Genotypes of TE insertions in each resequencing genome. i.e. Sam1.refereceTEinsertion and Sam1.Non-refereceTEinsertion.

TEindex AB      BC      AC      L       R       Genotype
Dref100 0       0       0       5       0       GG
Dref103 0       0       0       0       0       NA
Dref104 0       0       0       5       0       GG
Dref113 0       0       0       1       0       GG
Dref116 0       0       0       0       0       NA
Dref12  0       0       0       1       0       GG
Dref122 0       0       0       0       0       NA
Dref123 0       0       0       1       0       GG
Dref125 0       0       0       1       0       GG

CC indicates that the genotype in the corresponding accession was consistent with the reference genome, and GG indicates that the genotype in the accession was different from the reference genome, NA represents missing loci.

Usage

There are three main sequential steps to identify and genotype TE insertions, corresponding to 01.Reference_Nonreference_TEinsertion.pl, 02.get_TE_insertions_and_flankingSequences.pl, and 03.TE_insertions_genotype.pl.

Step 1: Identification of reference and non-reference TE insertions between different genomes.

perl 01.Reference_Nonreference_TEinsertion.pl  -h

Usage: perl 01.Reference_Nonreference_TEinsertion.pl  -query <query.info.lst>  -ref <reference.info.lst>  -TElib <EDTA.TElib.fa>  -bin <the path to smartie-sv>  -script <the path to scripts>

-query	[required] the query id and query genome files. Two columns (queryName queryGenomeFile).
-ref    [required] the reference information. Three columns (referenceName ReferenceGenomeFile ReferenceGff3)
-TElib  [required] the species TE library
-bin   	[required] the path to smartie-sv. i.e. /10t/caix/src/smartie-sv/bin
-script [required] the path to perl scripts

Step 2: extract flanking seuqences of each TE insertion

perl 02.get_TE_insertions_and_flankingSequences.pl  -h

Usage: perl 02.get_TE_insertions_and_flankingSequences.pl  -refGenome <ref.fa>  -refName  <ref>   -script <the path to scripts>  reference_TE.insertions.xls  non-reference_TE.insertions.xls

-refGenome	[required] the reference genome in fasta foramt.
-refName	  [required] the reference genome name, same as provided in the first step.
-script   	[required] the path to perl scripts

Step 3: Genotype TE insertions using short reads

perl 03.TE_insertions_genotype.pl -h

perl 03.TE_insertions_genotype.pl   -Fasta  <ref.referenceTEinsertions_and_flanking1kb.fasta>  -leftRead <Sam1_1.fq.gz>  -rightRead <Sam1_2.fq.gz> -samId <Sam1>  -output <Sam1.refereceTEinsertion>  -script <the path to scripts>  -threads <threads>

-Fasta	[required] the TE insertion and flanking sequences in fasta format
-leftRead	[required] left read
-rightRead	[required] right read
-samId	[required] sample name i.e. Sam1
-output	[required] TE genotype results
-script	[required] the path to scripts
-threads	[optional] threads  default: 6 cores

An example

we recommend that users modified their file format with those we provided in the testData.

cd  testData
sh  runMe.sh
cat runMe.sh

#!/bin/bash
path=`pwd`
script="${path}/../scripts/"

perl ../01.Reference_Nonreference_TEinsertion.pl  -query   query.info.lst  \
                                                  -ref     reference.info.lst  \
                                                  -TElib   EDTA.TElib.fa  \
                                                  -bin     /10t/caix/src/smartie-sv/bin  \
                                                  -script  ${script} 

perl ../02.get_TE_insertions_and_flankingSequences.pl  -refGenome ref.fa  \
                                                       -refName   ref  \
                                                       -script    ${script}

perl ../03.TE_insertions_genotype.pl      -Fasta  ref.Non-referenceTEinsertions_and_flanking1kb.fasta  \
                                          -leftRead Sam1_1.fq.gz  \
                                          -rightRead Sam1_2.fq.gz  \
                                          -samId  Sam1 \
                                          -output Sam1.Non-refereceTEinsertion  \
                                          -script  ${script}  \
                                          -threads 10 

perl ../03.TE_insertions_genotype.pl      -Fasta  ref.referenceTEinsertions_and_flanking1kb.fasta  \
                                          -leftRead Sam1_1.fq.gz  \
                                          -rightRead Sam1_2.fq.gz  \
                                          -samId  Sam1 \
                                          -output Sam1.refereceTEinsertion  \
                                          -script  ${script}  \
                                          -threads 10

Final results:
Phase 1: reference_TE.insertions.xls and non-reference_TE.insertions.xls
Pahse 2: Sam1.refereceTEinsertion and Sam1.Non-refereceTEinsertion

Citations

Xu Cai, Runmao Lin, Jianli Liang, Graham J. King, Jian Wu, Xiaowu Wang. (2022). Transposable element insertion: a hidden major source of domesticated phenotypic variation in Brassica rapa. Plant Biotechnology Journal. https://doi.org/10.1111/pbi.13807

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Identification of transposable element insertion polymorphisms (TIPs) based on a pan-genome and large-scale resequencing data

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