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Quality Assessment of Domesticated Animal Genome Assemblies

Bioinformatics and Biology Insights 2015年第Suppl 4期9S4卷 49-58页

作者： Seemann, Stefan E. Anthon, Christian Palasca, Oana Gorodkin, Jan Center for non-coding RNA in Technology and Health Department of Veterinary Clinical and Animal Sciences University of Copenhagen København Denmark

The era of high-throughput sequencing has made it relatively simple to sequence genomes and transcriptomes of individuals from many species. In order to analyze the resulting sequencing data, high-quality reference genome assemblies are required. However, this is still a major challenge, and many domesticated animal genomes still need to be sequenced deeper in order to produce high-quality assemblies. In the meanwhile, ironically, the extent to which rna seq and other next-generation data is produced frequently far exceeds that of the genomic sequence. Furthermore, basic comparative analysis is often affected by the lack of genomic sequence. Herein, we quantify the quality of the genome assemblies of 20 domesticated animals and related species by assessing a range of measurable parameters, and we show that there is a positive correlation between the fraction of mappable reads from rnaseq data and genome assembly quality. We rank the genomes by their assembly quality and discuss the implications for genotype analyses. © 2015, © 2015 SAGE Publications.

关键词： assembly quality domesticated animals genome assembly

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Targeting Micrornas With Small Molecules: From Dream to Reality

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CLINICAL PHARMACOLOGY & THERAPEUTICS 2010年第6期87卷 754-758页

作者： Zhang, S. Chen, L. Jung, E. J. Calin, G. A. Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Houston TX 77030 USA

Currently, one out of four deaths in the United States is due to cancer; therefore, every major therapeutic advance in cancer has the potential to save many lives. One of the most fascinating discoveries in the area of molecular oncology in the past decade is that, in cancer, alterations in both protein-coding genes and noncoding rnas, known as micrornas (mirnas), complement each other. In this article, we focus on a novel idea involving the use of small molecules to target overexpressed mirnas as a new therapy for diseases, particularly cancer, in humans. Clinical Pharmacology & Therapeutics (2010) 87 6, 754–758. doi: 10.1038/clpt.2010.46

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Gut microbiota:a new player in regulating immune-and chemo-therapy efficacy

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Cancer Drug Resistance 2020年第3期3卷 356-370页

作者： Simone Anfossi George A.Calin Department of Experimental Therapeutics The University of Texas MD Anderson Cancer CenterHoustonTX 77054USA. Center for RNA Interference and Non-coding RNAs The University of Texas MD Anderson Cancer CenterHoustonTX 77054USA.

Development of drug resistance represents the major cause of cancer therapy failure,determines disease progression and results in poor prognosis for cancer *** mechanisms are responsible for drug *** genetic modifications of cancer cells induce the alteration of expression of gene controlling specific pathways that regulate drug resistance:drug transport and metabolism;alteration of drug targets;DNA damage repair;and deregulation of apoptosis,autophagy,and pro-survival *** the other hand,a complex signaling network among the entire cell component characterizes tumor microenvironment and regulates the pathways involved in the development of drug *** microbiota represents a new player in the regulation of a patient’s response to cancer therapies,including chemotherapy and *** particular,commensal bacteria can regulate the efficacy of immune checkpoint inhibitor therapy by modulating the activation of immune responses to *** bacteria can also regulate the efficacy of chemotherapeutic drugs,such as oxaliplatin,gemcitabine,and ***,it has been shown that such bacteria can produce extracellular vesicles(EVs)that can mediate intercellular communication with human host ***,bacterial EVs carry rna molecules with gene expression regulatory ability that can be delivered to recipient cells of the host and potentially regulate the expression of genes involved in controlling the resistance to cancer *** the other hand,host cells can also deliver human EVs to commensal bacteria and similarly,regulate gene *** intercellular communication between commensal bacteria and host cells may thus represent a novel research area into potential mechanisms regulating the efficacy of cancer therapy.

关键词： Gut microbiota resistance chemotherapy immunotherapy immune checkpoint inhibitor extracellular vesicles mirnas cell-to-cell communication

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Fundamental Principles of Cancer Biology: Does It Have Relevance to the Perioperative Period?

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Current Anesthesiology Reports 2015年第3期5卷 250-256页

作者： Jiang, Li Nick, Alpa M. Sood, Anil K. Department of Gynecologic Oncology & Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston 77584 TX United States Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston 77584 TX United States Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center Houston 77584 TX United States

Malignant tumors are characterized by their ability to metastasize, which is the main cause of cancer-related mortality. Besides intrinsic alternations in cancer cells, the tumor microenvironment plays a pivotal role in tumor growth and metastasis. Ample evidence suggests that the perioperative period and the excision of the primary tumor can promote the development of metastases and can influence long-term cancer patient outcomes. The role of cancer biology and its impact on the perioperative period are of increasing interest. This review will present evidence regarding fundamental principles of cancer biology, especially tumor microenvironment, and discuss new therapeutic opportunities in the perioperative timeframe. We will also discuss the regulatory signaling that could be relevant to various aspects of surgery and surgical responses, which could facilitate the metastatic process by directly or indirectly affecting malignant tissues and the tumor microenvironment. We address the influences of surgery-related stress, anesthetic and analgesic agents, blood transfusion, hypothermia, and β-adrenergic blockade administration on tumor growth and metastasis. Through an improved understanding of these processes, we will provide suggestions for potential new perioperative approaches aimed at improving treatment outcomes of cancer patients. © 2015, Springer Science + Business Media New York.

关键词： Cancer biology Perioperative Therapeutics

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Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

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NATURE COMMUNICATIONS 2016年第1期7卷 10798-10812页

作者： Zhang, Dingxiao Park, Daechan Zhong, Yi Lu, Yue Rycaj, Kiera Gong, Shuai Chen, Xin Liu, Xin Chao, Hsueh-Ping Whitney, Pamela Calhoun-Davis, Tammy Takata, Yoko Shen, Jianjun Iyer, Vishwanath R. Tang, Dean G. Univ Texas MD Anderson Canc Ctr Dept Epigenet & Mol Carcinogenesis Smithville TX 78957 USA Univ Texas Austin Ctr Syst & Synthet Biol Inst Cellular & Mol Biol Dept Mol Biosci Austin TX 78712 USA Tongji Univ Sch Med East Hosp Res Ctr Translat MedCanc Stem Cell Inst Shanghai 2001120 Peoples R China Univ Texas MD Anderson Canc Ctr RNA Interference & Non Coding RNAs & Mol Carcinog Ctr Canc Epigenet Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr RNA Interference & Non Coding RNAs & Mol Carcinog Ctr Stem Cell Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr RNA Interference & Non Coding RNAs & Mol Carcinog Ctr Dev Biol Houston TX 77030 USA Univ Texas Austin Dept Chem Engn Austin TX 78712 USA

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep rna sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal rna (rrna) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rrna transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

关键词： Gene expression Prostate cancer

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Platelet Effects on Ovarian Cancer

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SEMINARS IN ONCOLOGY 2014年第3期41卷 378-384页

作者： Davis, Ashley N. Afshar-Kharghan, Vahid Sood, Anil K. Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Houston TX 77230 USA Univ Texas MD Anderson Canc Ctr Dept Benign Hematol Houston TX 77230 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77230 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77230 USA

Growing understanding of the role of thrombocytosis, high platelet turnover, and the presence of activated platelets in the circulation in cancer progression and metastasis has brought megakaryocytes into focus. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. However, before megakaryocyte/platelet-directed therapies can be considered for clinical use, understanding of the mechanism and biology of paraneoplastic thrombocytosis in malignancy is required. Here, we provide an overview of the clinical implications, biological significance, and mechanisms of paraneoplastic thrombocytosis in the context of ovarian cancer. (C) 2014 Elsevier Inc. All rights reserved.

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Prognostic SLC family genes promote cell proliferation,migration,and invasion in hepatocellular carcinoma

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生物化学与生物物理学报（英文版） 2021年第8期53卷 1065-1075页

作者： Xiao Fang Ying Liu Wangwen Xiao Nan Zhao Chunmiao Zhu Duonan yu Ya Zhao Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Clinical Medical College Yangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Medical CollegeYangzhou UniversityYangzhou 225009China

The solute carrier (SLC) superfamily genes encode more than 300 members that are responsible for the transmembrane transportation of many essential endogenous and exogenous compounds ranging from nutrients to *** are highly expressed in metabolic organs such as the liver,regulating the homeostasis of metabolites and the disposition of *** contrast to their well-studied roles in physiological and pharmacological processes,little is known about the relationship between SLCs and cancer ***,we aimed to explore the potential role of SLCs in progression and prognosis of hepatocellular carcinoma (HCC),one of the most commonly diag-nosed cancers and leading causes of death *** performing bioinformatics analyses of HCC dataset from The Cancer Genome Atlas database,we identified three novel signature SLCs(SLC51B,SLC22A15,and SLC2A1) that are indicative of poor *** functional analyses suggested the potential regulation of the three prognostic SLCs on cell proliferation and *** knockdown experiments performed in HCC cell lines showed that all three prognostic SLCs positively regulated the proliferation of HCC cells,among which SLC22A 15 and SLC2A 1 were required for migration and invasion of the cells,demonstrating remarkable consistency with the roles identified by bioinformatics methods in ***,our study provides a novel prognos-tic biomarker for HCC and reveals the significant roles of SLCs in HCC progression,which might have been undervalued in the past.

关键词： hepatocellular carcinoma prognostic signature SLC family genes proliferation metastasis

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PTMD: A Database of Human Disease-associated Post-translational Modifications

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Genomics, Proteomics & Bioinformatics 2018年第4期16卷 244-251页

作者： Haodong Xu Yongbo Wang Shaofeng Lin Wankun Deng Di Peng Qinghua Cui Yu Xue Department of Bioinformatics & Systems Biology MOE Key Laboratory of Molecular Biophysics College of Life Science and Technology and the Collaborative Innovation Center for Biomedical Engineering Huazhong University of Science and Technology Department of Biomedical Informatics School of Basic Medical Sciences MOE Key Laboratory of Molecular Cardiovascular Sciences Center for Non-coding RNA Medicine Peking University

Various posttranslational modifications （PTMs） participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in human diseases. Therefore, an integral resource of PTM–disease associations （PDAs）would be a great help for both academic research and clinical use. In this work, we reported PTMD,a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of diseaseassociated PTM events. By reconstructing a disease–gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http：//***.

关键词： Posttranslational modification Phosphorylation PTM-disease association Disease-gene network AKT1

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Computational strategies to search structured rnas in genomic sequence(and roads towards further analysis)

Computational strategies to search structured RNAs in genomi...

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2011国际基因组学大会

作者： Jan Gorodkin Center for non-coding RNA in Technology and Health IBHVUniversity of CopenhagenDenmark

A key application of early methods for computational rna folding was to aid interpretation of structure probing *** the years computational rna biology has developed in which improved energy models and the availability of multiple genomes have contributed substantially to the development of the *** methods that search for common rna structures in a set of co-regulated rnas have

关键词： rna and roads towards further analysis Computational strategies to search structured rnas in genomic sequence

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Interleukin-1β Promotes Ovarian Tumorigenesis through a p53/NF-κB-Mediated Inflammatory Response in Stromal Fibroblasts

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NEOPLASIA 2013年第4期15卷 409-+页

作者： Schauer, Isaiah Gregory Zhang, Jing Xing, Zhen Guo, Xiaoqing Mercado-Uribe, Imelda Sood, Anil K. Huang, Peng Liu, Jinsong Univ Texas MD Anderson Canc Ctr Dept Pathol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Mol Pathol Houston TX 77030 USA

Cancer has long been considered a disease that mimics an "unhealed wound," with oncogene-induced secretory activation signals from epithelial cancer cells facilitating stromal fibroblast, endothelial, and inflammatory cell participation in tumor progression. However, the underlying mechanisms that orchestrate cooperative interaction between malignant epithelium and the stroma remain largely unknown. Here, we identified interleukin-1 beta (IL-1 beta) as a stromal-acting chemokine secreted by ovarian cancer cells, which suppresses p53 protein expression in cancer-associated fibroblasts (CAFs). Elevated expression of IL-1 beta and cognate receptor IL-1R1 in ovarian cancer epithelial cells and CAFs independently predicted reduced overall patient survival, as did repressed nuclear p53 in ovarian CAFs. Knockdown of p53 expression in ovarian fibroblasts significantly enhanced the expression and secretion of chemokines IL-8, growth regulated oncogene-alpha (GRO-alpha), IL-6, IL-1 beta, and vascular endothelial growth factor (VEGF), significantly increased in vivo mouse xenograft ovarian cancer tumor growth, and was entirely dependent on interaction with, and transcriptional up-regulation of, nuclear factor-kappaB (NF-kappa B) p65. Our results have uncovered a previously unrecognized circuit whereby epithelial cancer cells use IL-1 beta as a communication factor instructing stromal fibroblasts through p53 to generate a protumorigenic inflammatory microenvironment. Attenuation of p53 protein expression in stromal fibroblasts generates critical protumorigenic functionality, reminiscent of the role that oncogenic p53 mutations play in cancer cells. These findings implicate CAFs as an important target for blocking inflammation in the tumor microenvironment and reducing tumor growth.

关键词： OVARIAN cancer RESEARCH INTERLEUKIN-1 CANCER invasiveness CANCER cells VASCULAR endothelial growth factors TUMORS -- Growth

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