Delivering FAIR Datasets for the Neglected Parasite Trichomonas vaginalis and Studies in Comparative Genomics

为被忽视的寄生虫阴道毛滴虫提供 FAIR 数据集和比较基因组学研究

基本信息

批准号：
10152873
负责人：
JANE M CARLTON
金额：
$ 8.44万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-17 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10152873
关键词：
Address Anaerobic Bacteria Animals Basic Science Biology Birds Cattle Centers for Disease Control and Prevention (U.S.)Characteristics Chromosomes Code Collaborations Comparative Genomic Analysis Complement DNA Transposable Elements Data Data Set Databases Deposition Dideoxy Chain Termination DNA Sequencing Disease Distant Eukaryotic Cell Family Sizes Fetus Funding Gene Family Genes Genome Genomics HIV Hi-C Human Inflammation Investments Knowledge Length Livestock Low Birth Weight Infant Manuals Maps Mastigophora Modeling Modernization Molecular National Institute of Allergy and Infectious Disease Not Hispanic or Latino Ontology Pain Parasites Parasitic infection Pathogenesis Pathogenicity Phenotype Pregnancy Premature Birth Prevalence Protein Databases Proteins Proteomics Publications Publishing RNA Repetitive Sequence Research Research Personnel Resources Risk Staphylococcus hominis Time Trichomonas Trichomonas Infections Trichomonas vaginalis Tritrichomonas foetus Uncertainty United States United States National Institutes of Health Update Vertebrates Woman Zoonoses aged annotation system arm base bioinformatics resource black women comparative genomics contig cross-species transmission data access data repository genomic data high standard improved multiple datasets neglect pathogen pet animal preference prevent public health priorities reference genome reproductive tract scaffold tenax tool transcriptome transcriptome sequencing transcriptomics transmission process virtual

项目摘要

Project Summary Trichomonas vaginalis is a flagellated, anaerobic protist that causes trichomoniasis, the most common non-viral sexually transmitted disease in humans, with prevalence in the USA estimated at 13% for non- Hispanic Black woman, and 5% in women aged 15-49 globally. Trichomoniasis can induce painful genital tract inflammation and discharge, increase the risk of HIV acquisition and transmission, and have pregnancy sequelae that include preterm delivery and low birth weight. The Centers for Disease Control and Prevention has identified trichomoniasis as a neglected parasitic infection and targeted it as a priority for public health action. In addition to T. vaginalis, virtually all known trichomonads are parasites or commensals of vertebrates, and include other human-infecting species (Trichomonas tenax, Pentatrichomonas hominis), devastating pathogens of birds (Trichomonas gallinae, Trichomonas stableri), an economically important pathogen of cattle (Tritrichomonas foetus), and pathogens of pets (Tr. foetus, P. hominis). Alarmingly, the host ranges of some trichomonads suggest that they can be agents of disease transmitted between humans and animals (i.e., zoonotic). Research on trichomonads remains neglected; genomic studies to date are primarily confined to T. vaginalis, a draft assembly of which (TvG3_2007) was published by our group in 2007 and deposited in public databases, including the NIH-funded Bioinformatics Resource Center (BRC) TrichDB, part of the EuPathDB suite of eukaryotic pathogen databases. While TvG3_2007 was groundbreaking and fruitful for research into the basic biology of T. vaginalis, it is highly fragmented due to the enormous complement of high copy number sequences, particularly long transposable elements (TEs), as well as expanded gene families. Uncertainty about gene and TE copy numbers due to assembly fragmentation is compounded by the enormous number (>70%) of the ~50,000 predicted protein-coding genes that could not be annotated beyond `hypothetical' or `conserved hypothetical' status. TvG3_2007 remains the only trichomonad genome deposited in TrichDB, and only its TE annotation has been updated since then. All of these factors are obstacles to studying T. vaginalis and other trichomonad pathogens at genomic, evolutionary, and molecular levels. This proposal seeks to remedy this situation by using modern databases and tools, including those available from the EuPathDB BRC, to annotate a new, high-quality, long-read T. vaginalis assembly that we have recently generated, and transfer that annotation to 17 assemblies that we and colleagues have also generated from eight trichomonad species. All data will be deposited in TrichDB, massively expanding the genomic assets available for T. vaginalis and trichomonad research. We will subsequently use the improved TrichDB resource to conduct comparative genomics across the trichomonads to elucidate differences in genome characteristics, gene family expansion, and importantly TE burden, in order to investigate correlates to host range and implications for potential zoonosis.

项目摘要阴道Trichomonas是一种鞭毛的，厌氧的原生物，导致毛oriasisis，最常见非病毒性传播疾病在人类中，在美国的普遍存在估计为13％西班牙裔黑人妇女，全球15-49岁的妇女中有5％。毛滴虫病可以诱导疼痛的生殖道炎症和排出，增加艾滋病毒收购和传播的风险，并怀孕后遗症包括早产和低出生体重。疾病控制与预防中心已将trichomoniasis确定为被忽视的寄生虫感染，并将其作为公共卫生的优先事项行动。除了阴道猪笼草外，几乎所有已知的trichomonads都是脊椎动物的寄生虫或共生，并包括其他人类感染物种（Trichomonas tenax，pentatrichomonas hominis），毁灭性鸟类的病原体（Trichomonas Gallinae，Trichomonas Stableri），这是牛经济上重要的病原体（Tritrichomonas胎儿）和宠物的病原体（Tr。Fetus，P。hominis）。令人震惊的是，一些主机范围 Trichomonads认为它们可以是人类和动物之间传播的疾病的药物（即，人畜共患病）。关于毛毛龙的研究仍然被忽略；迄今为止的基因组研究主要仅限于T。阴道，我们的小组于2007年出版了一项大会（TVG3_2007），并存放在公共场所数据库，包括NIH资助的生物信息学资源中心（BRC）TRICHDB，EUPATHDB的一部分真核病原体数据库的套件。虽然TVG3_2007是开创性的，并且富有成果 T.阴道的基本生物学，由于高拷贝数的巨大补体，它高度分散序列，尤其是长期可转移元件（TES）以及扩展的基因家族。不确定关于组装碎片引起的基因和TE拷贝数，由庞大的数字复合（>> 70％）在约50,000个预测的蛋白质编码基因中，无法在“假设”或 “保守的假设”状态。 TVG3_2007仍然是唯一存放在Trichdb的Trichomonad基因组，以及从那时起，只有其TE注释已更新。所有这些因素都是研究阴道猪笼草的障碍以及基因组，进化和分子水平的其他毛毛虫病原体。该提议试图通过使用现代数据库和工具，包括EupathDB BRC可用的情况，补救这种情况，注释我们最近生成的新的，高质量的长读T.阴道大会，并转移我们和同事也从八种trichomonad物种产生的17个集会的注释。所有数据都将存放在TrichDB中，并大量扩展了可用于阴道和阴道的基因组资产 Trichomonad研究。随后，我们将使用改进的TrichDB资源进行比较跨毛核的基因组学阐明了基因组特征的差异，基因家族膨胀，重要的是，为了研究与宿主范围的相关性以及对潜在的影响人畜共患病。