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

项目摘要 阴道毛滴虫是一种有鞭毛的厌氧原生生物，可引起最常见的 人类非病毒性传播疾病，在美国的患病率估计为13%， 西班牙裔黑人女性，以及全球15-49岁女性的5%。滴虫病可引起生殖道疼痛 炎症和分泌物，增加艾滋病毒获得和传播的风险，并有怀孕 后遗症包括早产和低出生体重。美国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 行动上除T.迷走性，几乎所有已知的毛滴虫都是脊椎动物的寄生虫或寄生虫， 并包括其他人类感染物种（毛滴虫tenax，五毛滴虫hominis），破坏性 禽类病原体（鸡毛滴虫、Stableri毛滴虫），一种重要的牛病原体 （胎儿三毛滴虫）和宠物病原体（Tr.胎儿，人疟原虫）。令人担忧的是，一些病毒的宿主范围 毛滴虫表明它们可能是人与动物之间传播的疾病的病原体（即， 动物传染病）。对毛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。 vagelet，本课题组于2007年发表了该汇编的草案（TvG3_2007），并公开存放 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 一套真核生物病原体数据库。虽然TvG3_2007是开创性的和富有成效的研究， T.由于高拷贝数的巨大补充，它是高度碎片化的。 序列，特别是长转座因子（TE），以及扩展的基因家族。不确定 关于基因和TE拷贝数由于组装碎片是复杂的巨大数量 （>70%）的~ 50，000预测的蛋白质编码基因，不能被注释超出“假设”或 “保守假设”状态。TvG3_2007仍然是TrichDB中唯一保藏的滴虫基因组， 从那时起，只有其TE注释被更新。这些因素都是T.阴道毛 和其他毛滴虫病原体在基因组，进化和分子水平。这项建议旨在 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， 来注释一个新的、高质量的、长时间阅读的T。我们最近生成的vagonists集合， 我们和同事也从8个毛滴虫物种中产生了17个组装体的注释。 所有数据都将存储在TrichDB中，大大扩展了T的基因组资产。迷走神经和 毛滴虫研究。我们随后将使用改进后的TrichDB资源进行比较 毛滴虫的基因组学，以阐明基因组特征，基因家族扩展， 重要的是TE负担，为了研究与宿主范围的相关性以及潜在的 人畜共患病

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.