Boquila: NGS read simulator to eliminate read nucleotide bias in sequence analysis

Abstract

Sequence content is heterogeneous throughout genomes. Therefore, Genome-wide NGS reads biased towards specific nucleotide profiles are affected by the genome-wide heterogeneous nucleotide distribution. Boquila generates sequences that mimic the nucleotide profile of true reads, which can be used to correct the nucleotide-based bias of genome-wide distribution of NGS reads. Boquila can be configured to generate reads from only specified regions of the reference genome. It also allows the use of input DNA sequencing to correct the bias due to the copy number variations in the genome. Boquila uses standard file formats for input and output data, and it can be easily integrated into any workflow for high-throughput sequencing applications.

The interplay of 3D genome organization with UV-induced DNA damage and repair

“…We first aimed to analyze the distribution of the simulated reads only, which reflects the nucleotide content bias of the genome in the 3D organization. Our simulation tool, Boquila, randomly selects genomic regions from the reference genome or input DNA sequencing data in a way that selected pseudo-reads will have a similar nucleotide frequency to the given NGS dataset ( 22 ). It takes two inputs: (i) reference genome or preexisting sequencing read data and (ii) actual NGS data (XR-seq or Damage-seq in this study).…”

“…Simulated datasets are generated using boquila ( 22 ) (v0.6). For HeLa cells, we used input DNA sequencing data accessed from SRA SRA PRJNA608124.…”