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Omics-based integrated analysis identified ATRX as a biomarker associated with glioma diagnosis and prognosis

Cancer Biology & Medicine 2019年第4期16卷 784-796页

作者： Yingbin Xie Yanli Tan Chao Yang Xuehao Zhang Can Xu Xiaoxia Qiao Jianglong Xu Shaohui Tian Chuan Fang Chunsheng Kang Department of Neurosurgery Affiliated Hospital of Hebei UniversityBaoding 071000China Department of Neurosurgery Hebei University Medical CollegeBaoding 071000China Department of Pathology Hebei University Medical CollegeBaoding 071000China Department of Pathology Affiliated Hospital of Hebei UniversityBaoding 071000China Lab of Neuro-oncology Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemTianjin Medical University General HospitalTianji n 300052China Department of Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China

Objective:ATRX is a multifunctional protein that is tightly regulated by and implicated in transcriptional regulation and chromatin *** studies have shown that genetic alterations in ATRX play a significant role in *** study aims to further determine the relationship between ATRX and glioma prognosis and identify possible mechanisms for exploring the biological significance of ATRX using large data ***:We used The Cancer Genome Atlas(TCGA)database and 130 immunohistochemical results to confirm the difference in ATRX mutations in high-and low-grade *** online analysis of the TCGA glioma datasets using the cBioPortal platform was performed to study the relationship between ATRX mutations and IDH1,TP53,CDKN2 A and CDKN2 B mutations in the corresponding TCGA glioma *** combination with clinical pathology data,the biological significance of the relationships were *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses and annotations of all adjacent genes in the network were performedin the Database for Annotation,Visualization and Integrated Discovery(DAVID)and R language.A protein-protein interaction(PPI)network was constructed,and the interactions of all adjacent nodes were analyzed by the String database and using Cytoscape ***:In the selected TCGA glioma datasets,a total of 2,228 patients were queried,21%of whom had ATRX alterations,which co-occurred frequently with TP53 and IDH1 *** alterations are associated with multiple critical molecular events,which results in a significantly improved overall survival(OS)*** low-grade gliomas,ATRX mutations are significantly associated with multiple important molecular events,such as ZNF274 and FDXR at mRNA and protein levels.A functional cluster analysis revealed that these genes played a role in chromatin binding and P53,and a link was observed between ATRX and IDH1 and TP53 in the interaction *** and TP53

关键词： ATRX mutation copy number variation glioma biomarkers

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Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield

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Molecular Plant 2022年第8期15卷 1310-1328页

作者： Baosheng Liao Xiaofeng Shen Li Xiang Shuai Guo Shiyu Chen Ying Meng Yu Liang Dandan Ding Junqi Bai Dong Zhang Tomasz Czechowski Yi Li Hui Yao Tingyu Mai Caroline Howard Chao Sun Haitao Liu Jiushi Liu Jin Pei Jihai Gao Jigang Wang Xiaohui Qiu Zhihai Huang Hongyi Li Ling Yuan Jianhe Wei lan Graham Jiang Xu Boli Zhang Shilin Chen Instituteof ChineseMateria Medica China Academyof ChineseMedical SciencesBeijing 100700China Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong Provincial Medical Products Administration the Second Clinical CollegeGuangzhou Universityof ChineseMedicineGuangzhou510006China Institute of Medicinal Plant Development Chinese Academy of Medical SciencesBeijing 100193China Artemisinin Research.Center China Academy of Chinese Medical SciencesBeijing 100700China Pharmacy College Chengdu University of Traditional Chinese MedicineChengdu 611137China Centre for Novel Agricultural Products Department of BiologyUniversity of YorkYorkUK Wellcome Sanger Institute Wellcome Trust Genome CampusHinxton CB101RQUK Kentucky Tobacco Research and Development Center University of KentuckyLexingtonKY 40546USA Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement&Guangdong Provincial Key Laboratory of Applied Botany South China Botanical GardenChineseAcademyof SciencesGuangzhou 510520China School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 300193China Chengdu University of Traditional Chinese Medicine Chengdu 611137China

Artemisia annua is the major natural source of artemisinin,an anti-malarial medicine commonly used ***,we present chromosome-level haploid maps for two *** strains with different artemisinin contents to explore the relationships between genomic organization and artemisinin ***-fidelity sequencing,optical mapping,and chromatin conformation capture sequencing were used to assemble the heterogeneous and repetitive genome and resolve the haplotypes of *** 5o,ooo genes were annotated for each haplotype genome,and a triplication event that occurred approximately 58.12million years ago was examined for the first time in this species.A total of 3,903,467-5,193,414 variants(SNPs,indels,and structural variants)were identified in the 1.5-Gb genome during pairwise comparison between haplotypes,consistent with the high heterozygosity of this *** analyses revealed a correlation between artemisinin concents and the copy number of amorpha-4,11-dienes *** correlation was further confirmed by resequencing of *** samples with varied artemisinin *** consensus sequencing of transcripts facilitated the detection of paralog ***,our study provides chromosome-level allele-aware genome assemblies for two *** strains and new insights into the biosynthesis of artemisinin and its regulation,which will contribute to conquering malaria worldwide.

关键词： Artemisia annua artemisinin haplotype chromosome amorpha-4 11-diene synthase copy number variation

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Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

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Protein & Cell 2023年第2期14卷 105-122页

作者： Fangyu Wang Xuan Liu Shaowen Li Chen Zhao Yumei Sun Kuan Tian Junbao Wang Wei Li Lichao Xu Jing Jing Juan Wang Sylvia MEvans Zhiqiang Li Ying Liu Yan Zhou Department of Neurosurgery Zhongnan hospital of Wuhan UniversityFrontier Science Center for Immunology and MetabolismMedical Research InstituteThe RNA InstituteCollege of Life SciencesWuhan UniversityWuhan 430071China Department of Neurology The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Skaggs School of Pharmacy Department of MedicineDepartment of PharmacologyUniversity of California at San DiegoLa JollaCA 92093USA

Glioblastoma multiforme(GBM),a highly malignant and heterogeneous brain tumor,contains various types of tumor and non-tumor *** GBM cells can trans-differentiate into non-neural cell types,including mural cells or endothelial cells(ECs),to support tumor growth and invasion remains *** we generated two genetic GBM models de novo in immunocompetent mouse brains,mimicking essential pathological and molecular features of human ***-tracing and transplantation studies demonstrated that,although blood vessels in GBM brains underwent drastic remodeling,evidence of trans-differentiation of GBM cells into vascular cells was barely ***,GBM cells could promiscuously express markers for mural cells during ***,single-cell RNA sequencing showed that patterns of copy number variations(CNVs)of mural cells and ECs were distinct from those of GBM cells,indicating discrete origins of GBM cells and vascular ***,single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate *** than expansion owing to trans-differentiation,vascular cell expanded by proliferation during ***,cross-lineage trans-differentiation of GBM cells is very unlikely to occur during *** findings advance understanding of cell lineage dynamics during gliomagenesis,and have implications for targeted treatment of GBMs.

关键词： glioblastoma mural cells endothelial cells trans-differentiation lineage tracing single-cell sequencing copy number variation

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CNV analysis of Meishan pig by nextgeneration sequencing and effects of AHR gene CNV on pig reproductive traits

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Journal of Animal Science and Biotechnology 2020年第3期11卷 667-677页

作者： Xianrui Zheng Pengju Zhao Kaijie Yang Chao Ning Haifei Wang Lei Zhou Jianfeng Liu National Engineering Laboratory for Animal Breeding Key Laboratory of Animal GeneticsBreeding and ReproductionMinistry of AgricultureCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Department of Animal Genetics Breeding and Reproduction and Molecular DesignCollege of Animal Science and TechnologyYangzhou UniversityYangzhou 225009China.

Background:Reproductive performance of livestock is an economically important aspect of global food *** Chinese Meishan pig is a prolific breed,with an average of three to five more piglets per litter than European breeds;however,the genetic basis for this difference is not well ***:In this study,we investigated copy number variations(CNVs)of 32 Meishan pigs and 29 Duroc pigs by nextgeneration sequencing.A genome-wide analysis of 61 pigs revealed 12,668 copy number variable regions(CNVRs)that were further divided into three categories based on copy number(CN)of the whole population,i.e.,gain(n=7,638),and loss(n=5,030)*** then compared Meishan and Duroc pigs and identified 17.17Mb of 6,387 CNVRs that only existing in Meishan pigs CNVRs that overlapped the reproduction-related gene encoding the aryl hydrocarbon receptor(AHR)*** found that normal AHR CN was more frequent than CN loss in four different pig *** association analysis showed that AHR CN had a positive effect on litter size(Pnumber born(Pnumber born alive(Pnumber of weaned piglets,and birth ***:The present study provides comprehensive CNVRs for Meishan and Duroc pigs through large-scale population *** results provide a supplement for the high-resolution map of copy number variation in the porcine genome and valuable information for the investigation of genomic structural variation underlying traits of interest in *** addition,the association results provide evidence for AHR as a candidate gene associated with reproductive traits that can be used as a genetic marker in pig breeding programs.

关键词： AHR copy number variation Meishan Next-generation sequencing Pig Reproduction

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Integrative Analysis of Genome,3D Genome,and Transcriptome Alterations of Clinical Lung Cancer Samples

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Genomics, Proteomics & Bioinformatics 2021年第5期19卷 741-753页

作者： Tingting Li Ruifeng Li Xuan Dong Lin Shi Miao Lin Ting Peng Pengze Wu Yuting Liu Xiaoting Li Xuheng He Xu Han Bin Kang Yinan Wang Zhiheng Liu Qing Chen Yue Shen Mingxiang Feng Xiangdong Wang Duojiao Wu Jian Wang Cheng Li Center for Bioinformatics School of Life SciencesCenter for Statistical SciencePeking UniversityBeijing 100871China BGI-Shenzhen Shenzhen 518083China Zhongshan Hospital Institute of Clinical Science Fudan UniversityShanghai Institute of Clinical BioinformaticsShanghai 200433China Fudan University Center for Clinical Bioinformatics Shanghai 200433China Department of Thoracic Surgery Zhongshan Hospital of Fudan UniversityShanghai 200032China School of Life Sciences Tsinghua UniversityBeijing 100084China BGI-Qingdao Qingdao 266426China Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics BGI-ShenzhenShenzhen 518083China iCarbonX Shenzhen 518053China Digital Life Research Institute Shenzhen 518110China State Key Laboratory of Proteomics National Center of Biomedical AnalysisInstitute of Basic Medical SciencesBeijing 100850China China National GeneBank BGI-ShenzhenShenzhen 518083China

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of ***,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical *** explore the 3D genome structure in clinical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing *** demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×10^(4)),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer *** also showed that Hi-C data can be used to infer CNVs and point mutations in *** integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene *** propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin *** study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

关键词： Lung cancer 3D genome copy number variation Clinical sample Integrative genomic analysis

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The Performance of Whole Genome Amplification Methods and Next-Generation Sequencing for Pre-Implantation Genetic Diagnosis of Chromosomal Abnormalities

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Journal of Genetics and Genomics 2015年第4期42卷 151-159页

作者： Na Li Li Wang Hui Wang Minyue Ma Xiaohong Wang Yi Li Wenke Zhang Jianguang Zhang David S.Cram Yuanqing Yao Department of Gynecology and Obstetrics Reproductive Medicine CenterTangdu HospitalFourth Military Medical University Department of Obstetrics and Gynecology Affiliated Hospital of Academy of Military Medical Sciences Department of Obstetrics and Gynecology Chinese PLA General Hospital Berry Genomics C.Limited

Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA （15 pg） and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification （MDA） system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing （CNV-Seq） was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient＇s cohort for uterine transplantation,

关键词： Single cells Whole genome amplification Next-generation sequencing copy number variation Pre-implantation genetic diagnosis

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eTumorType, An Algorithm of DiscriminatingCancer Types for Circulating Tumor Cells orCell-free DNAs in Blood

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Genomics, Proteomics & Bioinformatics 2017年第2期15卷 130-140页

作者： Jinfeng Zou Edwin Wang National Research Council Canada Montreal QC H4P 2R2 Canada Department of Experimental Medicine McGill University Montreal QC H3A 2B2 Canada Center Jor Bioinformatics McGill University Montreal QC H3G OB1 Canada Center for Health Genomics and Informatics University of Calgary Cumming School of Medicine Calgary AB T2N 4N1 Canada Department of Biochemistry & Molecular Biology University of Calgary Cumming School Of Medicine Calgary AB T2N 4NICanada Department of Medical Genetics University of Calgary Cumming School of Medicine Calgary AB T2N 4N1 Canada Department of Oncology University of Calgary Cumming School of Medicine Calgary AB T2N 4N1 Canada Alberta Children's Hospital Research Institute Calgary AB T2N 4N1 Canada Arnie Charbonneau Cancer Research Institute Calgary AB T2N 4Nl Canada O'Brien Institute for Public Health Calgary AB T2N 4N1 Canada

With the technology development on detecting circulating tumor cells(CTCs) and cellfree DNAs(cf DNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cf DNAs, making it possible to detect cancers using CTCs and cf DNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm,e Tumor Type, to identify cancer types based on copy number variations(CNVs) of the cancer founding clone. e Tumor Type integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. e Tumor Type has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. e Tumor Type produced high accuracies(0.86–0.96) and high recall rates(0.79–0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies(0.78–0.92)and recall rates(0.58–0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that e Tumor Type could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cf DNAs.

关键词： eTumorType Founding clone copy number variation Non-invasive detection Cancer

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Exploring the interplay of T cell receptor-V gene copy numbers and major histocompatibility complex selection pressure in avian species:Insights into immune system evolution and reproductive investment

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Avian Research 2024年第4期15卷 503-511页

作者： Lin Sun Chunhong Liang Shidi Qin Ying Zhu Ke He College of Animal Science and Technology College of Veterinary MedicineZhejiang Agriculture and Forestry UniversityKey Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang ProvinceZhejiang311300China Institute of Qinghai-Tibetan Plateau Southwest Minzu UniversitySichuan610000China

Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune *** association between major histocompatibility complex(MHC)genes and certain ecological factors in response to pathogen selection has been extensively studied;however,the role of the co-working molecule T cell receptor(TCR)remains poorly *** study aimed to analyze the copy numbers of TCR-V genes,the selection pressure(ωvalue)on MHC genes using available genomic data,and their potential ecological correlates across 93 species from 13 *** study was conducted using the publicly available genome data of *** findings suggested that phylogeny influences the variability in TCR-V gene copy numbers and MHC selection *** phylogenetic generalized least squares regression model revealed that TCR-Vαδcopy number and MHC-I selection pressure were positively associated with body *** size was correlated with MHC selection pressure,and Migration was correlated with TCR-Vβcopy *** analyses revealed that the TCR-Vβcopy number was positively correlated with MHC-IIB selection pressure,while the TCR-Vγcopy number was negatively correlated with MHC-I peptide-binding region selection *** findings suggest that TCR-V diversity is significant in adaptive evolution and is related to species’life-history strategies and immunological defenses and provide valuable insights into the mechanisms underlying TCR-V gene duplication and MHC selection in avian species.

关键词： copy number variation Immune genes MHC selection pressure Pathogen selection TCR-V gene

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An atlas of CNV maps in cattle, goat and sheep

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Science China(Life Sciences) 2021年第10期64卷 1747-1764页

作者： Yongzhen Huang Yunjia Li Xihong Wang Jiantao Yu Yudong Cai Zhuqing Zheng Ran Li Shunjin Zhang Ningbo Chen Hojjat Asadollahpour Nanaei Quratulain Hanif Qiuming Chen Weiwei Fu Chao Li Xiukai Cao Guangxian Zhou Shudong Liu Sangang He Wenrong Li Yulin Chen Hong Chen Chuzhao Lei Mingjun Liu Yu Jiang College of Animal Science and Technology Northwest A&F UniversityYangling 712100China College of Information Engineering Northwest A&F UniversityYangling 712100China Key Laboratory of Genetics Breeding and Reproduction of Grass feeding Livestock Ministry of AgricultureBiotechnology Research InstituteXinjiang Academy of Animal SciencesUrumqi 830026China National Institute for Biotechnology and Genetic Engineering(NIBGE) Faisalabad 577PunjabPakistan Pakistan Institute of Engineering&Applied Sciences(PIEAS) Nilore 45650IslamabadPakistan

copy number variation(CNV)is the most prevalent type of genetic structural variation that has been recognized as an important source of phenotypic variation in humans,animals and ***,the mechanisms underlying the evolution of CNVs and their function in natural or artificial selection remain ***,we generated CNV region(CNVR)datasets which were diverged or shared among cattle,goat,and sheep,including 886 individuals from 171 diverse *** 9 environmental factors for genome-wide association study(GWAS),we identified a series of candidate CNVRs,including genes relating to immunity,tick resistance,multi-drug resistance,and muscle *** number of CNVRs shared between species is significantly higher than expected(P<0.00001),and these CNVRs may be more persist than the single nucleotide polymorphisms(SNPs)shared between *** also identified genomic regions under long-term balancing selection and uncovered the potential diversity of the selected CNVRs close to the important functional *** study provides the evidence that balancing selection might be more common in mammals than previously considered,and might play an important role in the daily activities of these ruminant species.

关键词： copy number variation species-shared balancing selection ruminant livestock

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Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients

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Frontiers of Medicine 2023年第5期17卷 889-906页

作者： Xianggui Yuan Teng Yu Jianzhi Zhao Huawei Jiang Yuanyuan Hao Wen Lei Yun Liang Baizhou Li Wenbin Qian Department of Hematology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China Department of Pathology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhou215006China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou310009China

Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor *** study aimed to depict the genetic landscape of Chinese ***-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also *** variations were identified in all patients with a mean of 349,which did not significantly influence *** loss occurred in all samples,while gains were detected in 77.9%of the *** high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the ***79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.

关键词： primary central nervous system lymphoma whole-genome sequencing TMSB4X copy number variation gene utation

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