GSE117696
Refined detection and phasing of structural aberrations in pediatric acute lymphoblastic leukemia by linked-read whole genome sequencing (REH_RNAseq)
We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in an ALL cell line (REH) and primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The CNA, RNA-sequencing and linked-read WGS data for the REH ALL cell line has been deposited to GEO. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se. Overall design: RNA-sequencing libraries from REH were constructed with the TruSeq stranded total RNA protocol (RiboZero human/mouse/rat) according to the manufacturer's instructions (Illumina). The strand-specific libraries were sequenced on a NovaSeq 6000 instrument with 100 bp paired-end reads. Raw reads were trimmed to 65bp before STAR aignment.