Comprehensive single-cell genome analysis at nucleotide resolution using the PTA Analysis Toolbox

We developed a comprehensive bioinformatic workflow, called the PTA Analysis Toolbox (PTATO), to accurately detect single base substitutions, insertions-deletions (indels) and structural variants in PTA-based WGS data. PTATO includes a machine learning approach and filtering based on recurrency to distinguish PTA-artefacts from true mutations with high sensitivity (up to 90%), outperforming existing bioinformatic approaches. Our results show that PTATO enables studying somatic mutagenesis in the genomes of single cells with unprecedented sensitivity and accuracy.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001011126	Whole genome sequencing data of 57 single (PTA), clonally expanded and bulk human cells. Cells were obtained from bone marrow samples of patients with Fanconi Anemia (PMCFANCNN) or pediatric AML (PBNNNNN), from a clonal intestinal organoid line (STE0072/D-ORGWTNISL), from human cord blood (PMCCB15) and from a human lymphoblastoid cell line (PMCAHH1). WGS libraries were sequenced to ~15-30x genomic coverage (paired-end) on an Illumina Novaseq.	Illumina NovaSeq 6000	58

Publications	Citations
Comprehensive single-cell genome analysis at nucleotide resolution using the PTA Analysis Toolbox. Middelkamp S, Manders F, Peci F, van Roosmalen MJ, González DM, Bertrums EJM, van der Werf I, Derks LLM, Groenen NM, Verheul M, Trabut L, Pleguezuelos-Manzano C, Brandsma AM, Antoniou E, Reinhardt D, Bierings M, Belderbos ME, van Boxtel R. Cell Genom 3: 2023 100389	2