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，可引起滴虫病，最常见的 人类中的非病毒性传播疾病，美国估计非病毒性传播疾病的患病率为13% 西班牙裔黑人女性，在全球15-49岁的女性中占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，并怀孕 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，几乎所有已知的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(人毛滴虫、人毛滴虫)，具有破坏性 禽类的病原体(鸡毛滴虫、稳定毛滴虫)，一种重要的牛病原体 (胎儿滴虫)和宠物病原体(Tr.人疟原虫胎儿)。令人担忧的是，一些病毒的宿主范围 滴虫表明它们可能是人与动物之间传播疾病的病原体(即， 人畜共患病)。滴虫的研究仍然被忽视；到目前为止，基因组研究主要限于滴虫。 阴道，其组装草案(TvG3_2007)由本组于2007年发表并公开存放 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 一套真核病原体数据库。虽然TvG3_2007在研究方面具有开创性和丰硕成果 阴道毛滴虫的基本生物学，由于高拷贝数的巨大补充，它高度碎片化 序列，特别是长转座元件(TES)，以及扩展的基因家族。不确定度 关于基因和TE拷贝数由于组装断裂而产生的巨大数量 (&gt；70%)~50,000个预测的蛋白质编码基因中，不能超过“假设”或 “保守的假设”地位。TvG3_2007仍然是TrichDB中保存的唯一滴虫基因组，并且 自那以后，只有它的TE注释得到了更新。所有这些因素都是研究阴道毛滴虫的障碍。 和其他滴虫病原体在基因组、进化和分子水平上。这项建议旨在 通过使用现代数据库和工具来纠正这种情况，包括EuPathDB BRC提供的数据库和工具， 来注释我们最近生成的一个新的、高质量的、阅读很长的阴道毛滴虫组件，并将 我们和同事也从8个滴虫物种中生成了17个集合的注释。 所有数据都将存储在TrichDB中，大大扩展了可用于阴道毛滴虫和毛滴虫的基因组资产。 滴虫研究。随后，我们将利用改进后的TrichDB资源进行比较 通过滴虫基因组学来阐明基因组特征、基因家族扩展、 以及重要的TE负担，以调查与寄主范围的相关性和对潜在的影响 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.