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.

项目概要阴道毛滴虫是一种有鞭毛的厌氧原生生物，可引起滴虫病，滴虫病是最常见的疾病人类非病毒性传播疾病，在美国非病毒性传播疾病的患病率估计为 13% 西班牙裔黑人女性，占全球 15-49 岁女性的 5%。滴虫病可引起生殖道疼痛炎症和分泌物，增加艾滋病毒感染和传播的风险，以及怀孕后遗症包括早产和低出生体重。疾病控制和预防中心已将滴虫病确定为一种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。除了阴道毛滴虫外，几乎所有已知的毛滴虫都是脊椎动物的寄生虫或共生体，并包括其他感染人类的物种（特纳克斯毛滴虫、人五毛滴虫），具有毁灭性鸟类病原体（鸡毛滴虫、稳定毛滴虫），一种重要的牛经济病原体（胎儿三滴虫）和宠物病原体（胎儿三滴虫、人型三滴虫）。令人担忧的是，一些宿主范围毛滴虫表明它们可能是人类和动物之间传播疾病的媒介（即，人畜共患病）。对滴虫的研究仍然被忽视；迄今为止的基因组研究主要局限于 T. vaginalis，其大会草案 (TvG3_2007) 由我们小组于 2007 年出版并公开保存数据库，包括 NIH 资助的生物信息学资源中心 (BRC) TrichDB（EuPathDB 的一部分）真核病原体数据库套件。虽然 TvG3_2007 在研究方面具有开创性且富有成果阴道毛滴虫的基本生物学，由于高拷贝数的巨大补充，它是高度碎片化的序列，特别是长转座元件（TE），以及扩展的基因家族。不确定关于基因和 TE 拷贝数由于装配碎片而变得更加复杂 (>70%) 约 50,000 个预测的蛋白质编码基因无法在“假设”或“假设”之外进行注释 “保守的假设”状态。 TvG3_2007 仍然是唯一保存在 TrichDB 中的毛滴虫基因组，并且此后仅更新了其 TE 注释。所有这些因素都是研究阴道毛滴虫的障碍和其他毛滴虫病原体在基因组、进化和分子水平上的差异。该提案旨在通过使用现代数据库和工具（包括 EuPathDB BRC 提供的数据库和工具）来解决这种情况，注释我们最近生成的新的、高质量的、长读的阴道毛滴虫装配体，并转移我们和同事也从八种毛滴虫物种中生成了 17 个组件的注释。所有数据都将存储在 TrichDB 中，从而大规模扩展可用于阴道毛滴虫和滴虫研究。我们后续将利用改进后的TrichDB资源进行对比滴虫的基因组学，以阐明基因组特征、基因家族扩展、重要的是 TE 负担，以便研究与宿主范围的相关性以及对潜在的影响人畜共患病。