scholarly journals Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2

2018 ◽  
Author(s):  
Bo Zhou ◽  
Steve S. Ho ◽  
Stephanie U. Greer ◽  
Noah Spies ◽  
John M. Bell ◽  
...  

SUMMARYThe HepG2 cancer cell line is one of the most widely-used biomedical research and one of the main cell lines of ENCODE. Vast numbers of functional genomics and epigenomics datasets have been produced to characterize its biology. However, the correct interpretation such data requires an understanding of the cell line’s genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of HepG2 genome characteristics: copy numbers of chromosomal segments, SNVs and Indels (corrected for aneuploidy), phased haplotypes extending to entire chromosome arms, loss of heterozygosity, retrotransposon insertions, structural variants (SVs) including complex and somatic genomic rearrangements. We also identified allele-specific expression and DNA methylation genome-wide and assembled an allele-specific CRISPR/Cas9 targeting map.SIGNIFICANCEHaplotype-resolved and comprehensive whole-genome analysis of a widely-used cell line for cancer research and ENCODE, HepG2, serves as an essential resource for unlocking complex cancer gene regulation using a genome-integrated framework and also provides genomic context for the analysis of ~1,000 functional datasets to date on ENCODE for biological discovery. We also demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework.


2019 ◽  
Vol 47 (8) ◽  
pp. 3846-3861 ◽  
Author(s):  
Bo Zhou ◽  
Steve S Ho ◽  
Stephanie U Greer ◽  
Noah Spies ◽  
John M Bell ◽  
...  


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nuha Sweidan ◽  
Ezaldeen Esawi ◽  
Mohammad Ismail ◽  
Walhan Alshaer

Abstract Column chromatography (CC) analysis of methanol and butanol extracts of the aerial parts of Calortopis procera as well as the methanol extract of its latex, led to the isolation of 8 cardenolides, of which the structures were elucidated by NMR and HRESIMS spectroscopy. They also revealed several triterpenes and flavonoid glycoside. Based on the antiproliferative activity reported for cardenolides, the activity of calotropin and calotoxin was tested against two common cancer cell lines, human triple-negative breast cancer cell line (MDA-MB-231) and human lung adenocarcinoma cell line (A549). The high toxicity of the latex also encouraged performing the same test on the same cancer cell lines. The anti-proliferative activity of calotropin and calotoxin was compared to the methanol extract and the wax of the latex. The results showed that calotropin and calotoxin have significant cytotoxicity against MDA-MB-231 and A549 cell lines ranging from 0.046 to 0.072 μM compared to the methanol extract and the wax of its latex ranging from 0.47 to 58.41 μM. Moreover, the results showed lower toxicity of all treatments to the human skin fibroblasts compared to the toxicity to both MDA-MB-231 and A549 cancer cells lines except the higher toxicity of Methanolic extracts of C. procera latex to the MDA-MB-231 cells. In conclusion, C. procera is a medicinal plant with a wide spectrum of cardinolides including calotropin and calotoxin, which are promising agents for targeted cancer phytotherapy.



2017 ◽  
Author(s):  
Bo Zhou ◽  
Steve S. Ho ◽  
Stephanie U. Greer ◽  
Xiaowei Zhu ◽  
John M. Bell ◽  
...  

ABSTRACTK562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Such information is essential for the correct interpretation and understanding of the vast troves of existing functional genomics and epigenomics data for K562. We performed and integrated deep-coverage whole-genome (short-insert), mate-pair, and linked-read sequencing as well as karyotyping and array CGH analysis to identify a wide spectrum of genome characteristics in K562: copy numbers (CN) of aneuploid chromosome segments at high-resolution, SNVs and Indels (both corrected for CN in aneuploid regions), loss of heterozygosity, mega-base-scale phased haplotypes often spanning entire chromosome arms, structural variants (SVs) including small and large-scale complex SVs and non-reference retrotransposon insertions. Many SVs were phased, assembled, and experimentally validated. We identified multiple allele-specific deletions and duplications within the tumor suppressor geneFHIT. Taking aneuploidy into account, we re-analyzed K562 RNA-seq and whole-genome bisulfite sequencing data for allele-specific expression and allele-specific DNA methylation. We also show examples of how deeper insights into regulatory complexity are gained by integrating genomic variant information and structural context with functional genomics and epigenomics data. Furthermore, using K562 haplotype information, we produced an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize K562 as well as a framework for the analysis of other cancer genomes.



2001 ◽  
Vol 120 (5) ◽  
pp. A336-A336
Author(s):  
M SHIMADA ◽  
A ANDOH ◽  
Y ARAKI ◽  
Y FUJIYAMA ◽  
T BAMBA


2006 ◽  
Vol 175 (4S) ◽  
pp. 201-201 ◽  
Author(s):  
Isao Hara ◽  
Junya Furukawa ◽  
Kazuki Yamanaka ◽  
Yuji Yamada ◽  
Masato Fujisawa




Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
E Bautista ◽  
M Fragoso ◽  
R Pereda-Miranda


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