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▎Professor Li Cheng's research group submitted the chromatin that folds into a highly complex three-dimensional structure in the nucleus, and is dynamically regulated during the process of cell differentiation and proliferation
.
Chromatin conformation capture technologies such as Hi-C can capture genome-wide high-resolution chromatin interactions and help us better understand the relationship between three-dimensional genomes and cell functions
.
Lung cancer is currently one of the cancers with the highest incidence and death rate.
The omics research related to lung cancer covers genome, epigenetics, transcriptome and proteome, but there are few studies related to three-dimensional genome, especially direct use Research on clinical cancer samples
.
In this study, the researchers first demonstrated the feasibility of using a small number of cells (1×10^4) Hi-C experiments to study the three-dimensional genome of clinical lung cancer samples (Figure 1)
.
Then, the cancer and adjacent tissues were extracted from the two lung cancer patients, and Hi-C and RNA-seq sequencing were performed to obtain three-dimensional genome and transcriptome information
.
▲Figure 1: In the A549 cell line and 5534T clinical samples, the comparison of TAD detection in Hi-C experiments with different cell amounts (picture source: Contributed by Professor Li Cheng's research group) Through multi-omics data integration analysis of different levels of genomic changes, it is found: (1) The topological domains (TADs) and chromatin loops (loops) structure in clinical lung cancer samples have undergone significant changes
.
(2) Hi-C technology can be used not only to detect the three-dimensional structure of chromatin, but also to infer copy number variation (CNV) (Figure 2) and point mutations (SNV) in cancer
.
▲Figure 2: Identification of CNVs from Hi-C data
.
CNVs estimated from the Hi-C data of clinical patients and A549 cell line, red represents copy number increase, blue represents copy number decrease, and green represents normal copy number; TCGA row is from TCGA database (The Cancer Genome Atlas Research Network, The average copy number of 120 lung adenocarcinoma patients obtained in 2014) (Image source: Contributed by Professor Li Cheng’s research group) (3) The authors obtained the three-dimensional genome structure, CNV and mutation information of clinical lung cancer patients through Hi-C data.
Integrating analysis with RNA-seq data explored how genomic variation affects transcriptional regulation through three-dimensional genomes
.
There is a significant correlation between CNV, three-dimensional genome and gene expression
.
(4) This study emphasizes the importance of 3D genomics in clinical cancer sample research, and provides a data integration analysis process for future cancer 3D genomics research
.
The study was published on June 8, 2021 under the title "Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples" in the journal Genomics, Proteomics & Bioinformatics
.
Li Tingting (Academy of Military Sciences), Li Ruifeng (Tsinghua University), Dong Xuan (BGI), Shi Lin (Zhongshan Hospital of Fudan University), Lin Miao (Zhongshan Hospital of Fudan University) and Peng Ting (Peking University) are the joint articles of this paper.
One author
.
Professor Wu Duojiao from the Institute of Clinical Medicine, Zhongshan Hospital Affiliated to Fudan University, Wang Jian, Associate Dean of the Carbon Cloud Intelligent Digital Life Institute, and Researcher Li Cheng from the School of Life Sciences, Peking University, are the co-corresponding authors of the paper
.
This work was supported by the National Natural Science Foundation of China, the National Key Research and Development Program, and the "Polaris" high-performance computing platform of Peking University
.
Li Cheng's research group is interested in three-dimensional genomics experiments and analysis methods and their applications in regenerative biology and healthy aging.
They are currently recruiting postdoctoral fellows in bioinformatics and molecular biology.
Welcome to contact and exchange (http://3d-genome.
life/)
.
The title of this article: 123RF
.
Chromatin conformation capture technologies such as Hi-C can capture genome-wide high-resolution chromatin interactions and help us better understand the relationship between three-dimensional genomes and cell functions
.
Lung cancer is currently one of the cancers with the highest incidence and death rate.
The omics research related to lung cancer covers genome, epigenetics, transcriptome and proteome, but there are few studies related to three-dimensional genome, especially direct use Research on clinical cancer samples
.
In this study, the researchers first demonstrated the feasibility of using a small number of cells (1×10^4) Hi-C experiments to study the three-dimensional genome of clinical lung cancer samples (Figure 1)
.
Then, the cancer and adjacent tissues were extracted from the two lung cancer patients, and Hi-C and RNA-seq sequencing were performed to obtain three-dimensional genome and transcriptome information
.
▲Figure 1: In the A549 cell line and 5534T clinical samples, the comparison of TAD detection in Hi-C experiments with different cell amounts (picture source: Contributed by Professor Li Cheng's research group) Through multi-omics data integration analysis of different levels of genomic changes, it is found: (1) The topological domains (TADs) and chromatin loops (loops) structure in clinical lung cancer samples have undergone significant changes
.
(2) Hi-C technology can be used not only to detect the three-dimensional structure of chromatin, but also to infer copy number variation (CNV) (Figure 2) and point mutations (SNV) in cancer
.
▲Figure 2: Identification of CNVs from Hi-C data
.
CNVs estimated from the Hi-C data of clinical patients and A549 cell line, red represents copy number increase, blue represents copy number decrease, and green represents normal copy number; TCGA row is from TCGA database (The Cancer Genome Atlas Research Network, The average copy number of 120 lung adenocarcinoma patients obtained in 2014) (Image source: Contributed by Professor Li Cheng’s research group) (3) The authors obtained the three-dimensional genome structure, CNV and mutation information of clinical lung cancer patients through Hi-C data.
Integrating analysis with RNA-seq data explored how genomic variation affects transcriptional regulation through three-dimensional genomes
.
There is a significant correlation between CNV, three-dimensional genome and gene expression
.
(4) This study emphasizes the importance of 3D genomics in clinical cancer sample research, and provides a data integration analysis process for future cancer 3D genomics research
.
The study was published on June 8, 2021 under the title "Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples" in the journal Genomics, Proteomics & Bioinformatics
.
Li Tingting (Academy of Military Sciences), Li Ruifeng (Tsinghua University), Dong Xuan (BGI), Shi Lin (Zhongshan Hospital of Fudan University), Lin Miao (Zhongshan Hospital of Fudan University) and Peng Ting (Peking University) are the joint articles of this paper.
One author
.
Professor Wu Duojiao from the Institute of Clinical Medicine, Zhongshan Hospital Affiliated to Fudan University, Wang Jian, Associate Dean of the Carbon Cloud Intelligent Digital Life Institute, and Researcher Li Cheng from the School of Life Sciences, Peking University, are the co-corresponding authors of the paper
.
This work was supported by the National Natural Science Foundation of China, the National Key Research and Development Program, and the "Polaris" high-performance computing platform of Peking University
.
Li Cheng's research group is interested in three-dimensional genomics experiments and analysis methods and their applications in regenerative biology and healthy aging.
They are currently recruiting postdoctoral fellows in bioinformatics and molecular biology.
Welcome to contact and exchange (http://3d-genome.
life/)
.
The title of this article: 123RF