高速シークエンサーを用いたＨＴＬＶ－１クローナリティー解析

使用高速测序仪进行 HTLV-1 克隆性分析

• 批准号: 12J06916
• 负责人: フィルジ サナーズ (2014)
• 金额: $ 1.73万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12J06916/
• 关键词: HTLV-1; adult T-cell leukemia; NGS technology; HTLV-1 integration sites; HTLV-1-Clonality; in- silico analysis; absolute size of clones; JSPFAD; 成人T細胞白血病(ATL); HTLV-1ウイルス; クローナリティー解析; Integration site 解析; 次世代シークエンサー; Validation of Methodology

We took advantage of NGS technology, a unique tag system, and an original in- silico analysis pipeline to develop and internally validate a new high-throughput methodology, which enables specific isolation of HTLV-1 integration sites, and an accurate measurement of the absolute size of clones from various kinds of clinical samples even those with very low PVLs [Firouzi et al. Genome medicine 2014]. In addition, we have started analyzing clinical samples with different disease status and PVLs. We could find differing clonality patterns specific to asymptomatic carriers (ACs) and different subtypes of ATL. Hence we proposed that HTLV-1-infected individuals may be classifiable into different groups, based on their clonality patterns, ultimately affecting their diagnosis and choice of therapy. Moreover, in a cohort study, we monitored rare sets of sequential clinical samples including: samples with no change in their clinical status, and those who progressed to a more advance clinical state, as well as patients before and after medical therapy. Our initial data showed that the changes in the clonal composition of infected individuals appear to be a beneficial prognostic indicator for early detection of ATL onset. Taken together, the realization of potential applications of our methodology may have far-reaching impacts on the diagnosis, prognosis, and clinical decision-making for treatment of infected individuals. Thus, a larger scale cohort study to evaluate the clonal composition of infected cells is currently in progress.

我们利用NGS技术、独特的标签系统和原创的硅内分析管道来开发和内部验证一种新的高通量方法，该方法能够特定分离HTLV-1整合位点，并从各种临床样本中准确测量克隆的绝对大小，即使是那些PVL非常低的样本[Firouzi等人。基因组医学2014年]。此外，我们已经开始分析不同疾病状态和PVL的临床样本。我们可以发现不同的无症状携带者(ACS)和不同的ATL亚型特有的克隆模式。因此，我们提出HTLV-1感染者可以根据其克隆性模式被分成不同的组，最终影响他们的诊断和治疗选择。此外，在一项队列研究中，我们监测了几组罕见的连续临床样本，包括：临床状态没有变化的样本，进展到更高级临床状态的样本，以及药物治疗前后的患者。我们的初步数据显示，感染个体克隆组成的变化似乎是早期发现ATL发病的一个有利的预后指标。综上所述，我们方法学的潜在应用可能会对感染者的诊断、预后和临床决策产生深远的影响。因此，目前正在进行一项更大规模的队列研究，以评估感染细胞的克隆性成分。

项目成果

Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites.

• DOI: 10.1186/gm568
• 发表时间: 2014
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Firouzi S;López Y;Suzuki Y;Nakai K;Sugano S;Yamochi T;Watanabe T
• 通讯作者: Watanabe T

A new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites

一种基于原病毒整合位点研究 HTLV-1 感染细胞克隆性的新高通量方法

• 发表时间: 2014
• 作者: Sanaz Firouzi;Tadanori Yamochi;Yosvany Lopez;Yutaka Suzuki;Kenta Nakai;Sumio Sugano;Toshiki Watanabe
• 通讯作者: Toshiki Watanabe

Development of a new high-throughput method to investigate T-cell-clonality and integration site preference among HTLV 1-infected individuals(ポスター)

开发一种新的高通量方法来研究 HTLV 1 感染者的 T 细胞克隆性和整合位点偏好（海报）

• 发表时间: 2013
• 作者: Sanaz Firouzi;Tadanori Yamochi;Yosvany Lopez;Yutaka Suzuki;Kenta Nakai;Sumio Sugano;Toshiki Watanabe;Firouzi Sanaz
• 通讯作者: Firouzi Sanaz

Development of a new high-throughput method to investigate T-cell-clonalityand integration site preference among HTLV-1 infected individuals

开发一种新的高通量方法来研究 HTLV-1 感染个体中的 T 细胞克隆性和整合位点偏好

• 发表时间: 2012
• 作者: Sanaz Firouzi;Tadanori Yamochi;Yosvany Lopez;Yutaka Suzuki;Kenta Nakai;Sumio Sugano;Toshiki Watanabe;Firouzi Sanaz;Firouzi Sanaz;Firouzi Sanaz;Firouzi Sanaz
• 通讯作者: Firouzi Sanaz

Development and validation of a new high-throughput method to investigate T-cell-clonality and integration site preference among HTLV-1-infected individuals

开发和验证一种新的高通量方法来研究 HTLV-1 感染个体中的 T 细胞克隆性和整合位点偏好

• 发表时间: 2012
• 作者: Sanaz Firouzi;Tadanori Yamochi;Yosvany Lopez;Yutaka Suzuki;Kenta Nakai;Sumio Sugano;Toshiki Watanabe;Firouzi Sanaz;Firouzi Sanaz;Firouzi Sanaz;Firouzi Sanaz;Firouzi Sanaz;Firouzi Sanaz
• 通讯作者: Firouzi Sanaz