RT Journal Article
SR Electronic
T1 Chromatin conformation capture (Hi-C) sequencing of patient-derived xenografts: analysis guidelines
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.17.343814
DO 10.1101/2020.10.17.343814
A1 Mikhail G. Dozmorov
A1 Katarzyna M. Tyc
A1 Nathan C. Sheffield
A1 David C. Boyd
A1 Amy L. Olex
A1 Jason Reed
A1 J. Chuck Harrell
YR 2020
UL http://biorxiv.org/content/early/2020/10/19/2020.10.17.343814.abstract
AB Sequencing of patient-derived xenograft (PDX) mouse models allows investigation of the molecular mechanisms of human tumor samples engrafted in a mouse host. Thus, both human and mouse genetic material is sequenced. Several methods have been developed to remove mouse sequencing reads from RNA-seq or exome sequencing PDX data and improve the downstream signal. However, for more recent chromatin conformation capture technologies (Hi-C), the effect of mouse reads remains undefined.We evaluated the effect of mouse read removal on the quality of Hi-C data using in silico created PDX Hi-C data with 10% and 30% mouse reads. Additionally, we generated two experimental PDX Hi-C datasets using different library preparation strategies. We evaluated three alignment strategies (Direct, Xenome, Combined) and three processing pipelines (Juicer, HiC-Pro, HiCExplorer) on the quality of Hi-C data.Removal of mouse reads had little-to-no effect on data quality than the results obtained with Direct alignment strategy. Juicer pipeline extracted the most useful information from PDX Hi-C data. However, library preparation strategy had the largest effect on all quality metrics. Together, our study presents comprehensive guidelines on PDX Hi-C data processing.Competing Interest StatementThe authors have declared no competing interest.