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  • Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression [Figure presented]

    • 摘要:

      Background: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. Objective: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa. Design, setting, and participants: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. Outcome measurements and statistical analysis: The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses. Results and limitations: We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated. Conclusions: There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression. Patient summary: We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment. We presented the first comprehensive genetic alteration landscape of prostate cancer in Chinese men and identify novel genes and progression pathways that may help advance prostate cancer diagnosis, prognosis, and personalized medicine.

    • 作者:

      Shancheng Ren    卫功宏    Liu Dongbing    Liguo Wang    Yong Hou    Zhu Shida    Peng Lihua    Zhang Qin    Cheng Yanbing    Su Hong    Zhou Xiuqing    Jibin Zhang    Li Fuqiang    Hancheng Zheng    Zhao Zhikun    Changjun Yin    He Zengquan    Xin Gao    Zhau Haiyen E.    Chu Chia-Yi    Wu Jason Boyang    Colin Collins    Volik Stas    Bell Robert H.    Jiaoti Huang    Kui Wu    Danfeng Xu    Ye Dingwei    Yongwei Yu    Zhu Lianhui    Qiao Meng    Lee Hang Mao    Yang Yuehong    Zhu Yasheng    Shi Xiaolei    Rui Chen    王洋    徐卫东    Cheng Yan-Qiong    许传亮    Xu Gao    Tie Zhou    Bo Yang    Jianguo Hou    Liu Li    Zhensheng Zhang    朱耀    Qin Chao    Shao Pengfei    Pang Jun    Chung Leland W.K.    徐剑锋    Chin lee Wu    Zhong Wei-De    Xu Xun    Yingrui Li    Xiuqing Zhang    Wang Jian    杨焕明     Wang Jun    黄浩杰    孙颖浩   

    • 刊名:

      European Urology

    • 在线出版时间:

      2018

  • Characterization of viral RNA splicing using whole-transcriptome datasets from host species

    • 摘要:

      RNA alternative splicing (AS) is an important post-transcriptional mechanism enabling single genes to produce multiple proteins. It has been well demonstrated that viruses deploy host AS machinery for viral protein productions. However, knowledge on viral AS is limited to a few disease-causing viruses in model species. Here we report a novel approach to characterizing viral AS using whole transcriptome dataset from host species. Two insect transcriptomes (Acheta domesticus and Planococcus citri) generated in the 1,000 Insect Transcriptome Evolution (1KITE) project were used as a proof of concept using the new pipeline. Two closely related densoviruses (Acheta domesticus densovirus, AdDNV, and Planococcus citri densovirus, PcDNV, Ambidensovirus, Densovirinae, Parvoviridae) were detected and analyzed for AS patterns. The results suggested that although the two viruses shared major AS features, dramatic AS divergences were observed. Detailed analysis of the splicing junctions showed clusters of AS events occurred in two regions of the virus genome, demonstrating that transcriptome analysis could gain valuable insights into viral splicing. When applied to large-scale transcriptomics projects with diverse taxonomic sampling, our new method is expected to rapidly expand our knowledge on RNA splicing mechanisms for a wide range of viruses.

    • 作者:

      Zhou Chengran    Liu Shanlin    Song Wenhui    Luo Shiqi    Meng Guanliang    Yang Chentao    Yang Hua    Ma Jinmin    Wang Liang    Gao Shan    Wang Jian    杨焕明     Zhao Yun    Wang Hui    Xin Zhou   

    • 刊名:

      Scientific Reports

    • 在线出版时间:

      2018

  • SOAPnuke: A MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data

    • 摘要:

      Quality control (QC) and preprocessing are essential steps for sequencing data analysis to ensure the accuracy of results. However, existing tools cannot provide a satisfying solution with integrated comprehensive functions, proper architectures, and highly scalable acceleration. In this article, we demonstrate SOAPnuke as a tool with abundant functions for a "QC-Preprocess-QC" workflow and MapReduce acceleration framework. Four modules with different preprocessing functions are designed for processing datasets from genomic, small RNA, Digital Gene Expression, and metagenomic experiments, respectively. As a workflow-like tool, SOAPnuke centralizes processing functions into 1 executable and predefines their order to avoid the necessity of reformatting different files when switching tools. Furthermore, the MapReduce framework enables large scalability to distribute all the processing works to an entire compute cluster. We conducted a benchmarking where SOAPnuke and other tools are used to preprocess a ~30× NA12878 dataset published by GIAB. The standalone operation of SOAPnuke struck a balance between resource occupancy and performance. When accelerated on 16 working nodes with MapReduce, SOAPnuke achieved ~5.7 times the fastest speed of other tools.

    • 作者:

      Chen Yuxin    Chen Yongsheng    Shi Chun Mei    Huang Zhibo    Zhang Yong    Li Shengkang    Li Yan    Ye Jia    Yu Chang    Li Zhuo    Xiuqing Zhang    Wang Jian    杨焕明     Fang Lin    Chen Qiang   

    • 刊名:

      GigaScience

    • 在线出版时间:

      2018

  • Earth BioGenome Project: Sequencing life for the future of life

    • 摘要:

      Increasing our understanding of Earth's biodiversity and responsibly stewarding its resources are among the most crucial scientific and social challenges of the new millennium. These challenges require fundamental new knowledge of the organization, evolution, functions, and interactions among millions of the planet's organisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biology that aims to sequence, catalog, and characterize the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces, including data-sharing policies that ensure a permanent, freely available resource for future scientific discovery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describe scientific and organizational challenges in executing such an ambitious project, and the structure proposed to achieve the project's goals. The far-reaching potential benefits of creating an open digital repository of genomic information for life on Earth can be realized only by a coordinated international effort.

    • 作者:

      Harris Lewin    Gene Robinson    John Kress    Baker William J.    Coddington Jonathan    Crandall Keith A.    Richard Durbin    Edwards Scott V.    Forest Félix    Gilbert M. Thomas P.    Goldstein Melissa M.    Igor Grigoriev    Hackett Kevin J.J.    David Haussler    Erich Jarvis    Johnson Warren E.    Aristides Patrinos    Stephen Richards    Castilla-Rubio Juan Carlos    Van Sluys Marie-Anne    Soltis Pamela S.    徐迅    杨焕明     张国捷   

    • 刊名:

      Proceedings of the National Academy of Sciences of the United States of America

    • 在线出版时间:

      2018

  • Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 Genomes Project: Implications for interpretation of structural variation in genomes and the future of clinical cytogenetics

    • 摘要:

      Purpose: Recent studies demonstrate that whole-genome sequencing enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in the 1000 Genomes Project without knowing which bands were affected. Methods: The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparent BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold). Results: With this approach, we detected four reciprocal balanced translocations and four inversions, ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and polymerase chain reaction studies. One of these DNAs has a subtle translocation that is not readily identified by chromosome analysis because of the similarity of the banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene. Conclusion: Our study demonstrates the extension of utilizing low-pass whole-genome sequencing for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.

    • 作者:

      Dong Zirui    Wang Huilin    Chen Haixiao    Jiang Hui    Yuan Jianying    Yang Zhenjun    Wang Wen-Jing    Xu Fengping    Xiaosen Guo    Cao Ye    Zhu Zhenzhen    Geng Chunyu    Cheung Wan Chee    Kwok Yvonne K.    杨焕明     Leung Tak Yeung    Morton Cynthia C.    Sauwai Cheung    Kwongwai Choy   

    • 刊名:

      Genetics in Medicine

    • 在线出版时间:

      2018

  • The landscape of somatic mutation in sporadic Chinese colorectal cancer

    • 摘要:

      Colorectal cancer is the fifth prevalent cancer in China. Nevertheless, a largescale characterization of Chinese colorectal cancer mutation spectrum has not been carried out. In this study, we have performed whole exome-sequencing analysis of 98 patients' tumor samples with matched pairs of normal colon tissues using Illumina and Complete Genomics high-throughput sequencing platforms. Canonical CRC somatic gene mutations with high prevalence ( > 10%) have been verified, including TP53, APC, KRAS, SMAD4, FBXW7 and PIK3CA. PEG3 is identified as a novel frequently mutated gene (10.6%). APC and Wnt signaling exhibit significantly lower mutation frequencies than those in TCGA data. Analysis with clinical characteristics indicates that APC gene and Wnt signaling display lower mutation rate in lymph node positive cancer than negative ones, which are not observed in TCGA data. APC gene and Wnt signaling are considered as the key molecule and pathway for colorectal cancer initiation, and these findings greatly undermine their importance in tumor progression for Chinese patients. Taken together, the application of nextgeneration sequencing has led to the determination of novel somatic mutations and alternative disease mechanisms in colorectal cancer progression, which may be useful for understanding disease mechanism and personalizing treatment for Chinese patients.

    • 作者:

      Liu Zhe    Yang Chao    Xiangchun Li    Luo Wen    Roy Bhaskar    Xiong Teng    Xiuqing Zhang    杨焕明     王健    Ye Zhenhao    Chen Yang    Song Jinghe    Ma Shuai    Zhou Yong    Min Yang    Xiaodong Fang    杜杰   

    • 刊名:

      Oncotarget

    • 在线出版时间:

      2018

  • Genomic full-length sequence of HLA-B*15:178 was identified by full-length group-specific sequencing

    • 摘要:

      Genomic full-length sequence of HLA-B*15:178 was identified by a group-specific sequencing approach from China.

    • 作者:

      He L. M.    杨焕明     Xu Yunping    Hong W. X.   

    • 刊名:

      HLA

    • 在线出版时间:

      2018

  • Pilot study of expanded carrier screening for 11 recessive diseases in China: results from 10,476 ethnically diverse couples

    • 摘要:

      Expanded carrier screening (ECS) has been demonstrated to increase the detection rate of carriers compared with traditional tests. The aim of this study was to assess the potential value of ECS for clinical application in Southern China, a region with high prevalence of thalassemia and with diverse ethnic groups, and to provide a reference for future implementations in areas with similar population characteristics. A total of 10,476 prenatal/preconception couples from 34 self-reported ethnic groups were simultaneously tested and analyzed anonymously for 11 Mendelian disorders using targeted next-generation sequencing. Overall, 27.49% of individuals without self-reported family history of disorders were found to be carriers of at least 1 of the 11 conditions, and the carrier frequency varied greatly between ethnic groups, ranging from 4.15% to 81.35%. Furthermore, 255 couples (2.43%) were identified as carrier couples at an elevated risk having an affected baby, sixty-five of which would not have been identified through the existing screening strategy, which only detects thalassemia. The modeled risk of fetuses being affected by any of the selected disorders was 531 per 100,000 (95% CI, 497–567 per 100,000). Our data demonstrate the feasibility of ECS, and provide evidence that ECS is a promising alternative to traditional one-condition screening strategies. The lessons learned from this experience should be applicable for other countries or regions with diverse ethnic groups.

    • 作者:

      Zhao Sumin    Xiang Jiale    Fan Chunna    Asan    Shang Xuan    Xinhua Zhang    Chen Yan    Zhu Bao-Sheng    Cai Wang-Wei    Shaoke Chen    Ren Cai    Guo Xiaoling    Zhang Chonglin    Zhou Yuqiu    Huang Shuodan    Liu Yan-hui    Chen Biyan    Yan Shanhuo    Chen Yajun    Ding Hongmei    Guo Fengyu    Wang YaoShen    Zhong Wenwei    Zhu Yaping    Wang Yaling    Chen Chao    Li Yun    Huang Hui    Mao Mao    Yin Ye    Wang Jian    杨焕明     Xiangmin Xu    Sun Jun    Peng Zhiyu   

    • 刊名:

      European Journal of Human Genetics

    • 在线出版时间:

      2018

  • Copy number variation profile in noninvasive prenatal testing (NIPT) can identify co-existing maternal malignancies: Case reports and a literature review

    • 摘要:

      Objective: The coexistence of maternal malignancy and pregnancy has received increasing attention in Noninvasive prenatal testing (NIPT) studies. Malignancy in pregnant women potentially affects the copy number variation (CNV) profile in NIPT results. Only one case of hematologic cancer has been reported in a Hong-Kong pregnant women, and solid tumors have never been reported in pregnant Chinese women. Case report: The patients with dysgerminoma and cervical cancer showed aberrant chromosomal aneuploidies in NIPT and concordant patterns of genome disruption in tumor tissues. The genomic aberrations in the gastric cancer patient had similar copy number variation pattern of gastric cancer. Conclusion: The findings in this study and the literature review further validate the effect of maternal malignancy on the copy number variation profile in NIPT data and strengthen the possibility of detecting malignant tumors with NIPT in the future.

    • 作者:

      Xing Ji    Chen Fang    Zhou Yafeng    Li Jia    Yuan Yuying    Mo Yu    Liu Qiang    Tseng Jen-Yu    Shih-Chieh Lin Diego    Shen S-H    Liu Yu    Ye Weiping    Cheung Yuen Nei    Yuen Ka Yiu    Lin Siyuan    Fu    Hongyun Zhang    Liu Na    Wang Jian    杨焕明     Wang Yuying    Li Shen    Fan Shushu    Jin Xin    Mao Mao    Sung Pi-Lin   

    • 刊名:

      Taiwanese Journal of Obstetrics and Gynecology

    • 在线出版时间:

      2018

  • MetaPGN: a pipeline for construction and graphical visualization of annotated pangenome networks

    • 摘要:

      Pangenome analyses facilitate the interpretation of genetic diversity and evolutionary history of a taxon. However, there is an urgent and unmet need to develop new tools for advanced pangenome construction and visualization, especially for metagenomic data. Here, we present an integrated pipeline, named MetaPGN, for construction and graphical visualization of pangenome networks from either microbial genomes or metagenomes. Given either isolated genomes or metagenomic assemblies coupled with a reference genome of the targeted taxon, MetaPGN generates a pangenome in a topological network, consisting of genes (nodes) and gene-gene genomic adjacencies (edges) of which biological information can be easily updated and retrieved. MetaPGN also includes a self-developed Cytoscape plugin for layout of and interaction with the resulting pangenome network, providing an intuitive and interactive interface for full exploration of genetic diversity. We demonstrate the utility of MetaPGN by constructing Escherichia coli pangenome networks from five E. coli pathogenic strains and 760 human gut microbiomes,revealing extensive genetic diversity of E. coli within both isolates and gut microbial populations. With the ability to extract and visualize gene contents and gene-gene physical adjacencies of a specific taxon from large-scale metagenomic data, MetaPGN provides advantages in expanding pangenome analysis to uncultured microbial taxa.

    • 作者:

      Peng Ye    Tang Shanmei    Wang Dan    Zhong Huanzi    Huijue Jia    Cai Xianghang    Zhang Zhaoxi    Xiao Minfeng    杨焕明     Wang Jian    Karsten Kristiansen    Xu Xun    Junhua Li   

    • 刊名:

      GigaScience

    • 在线出版时间:

      2018

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