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

我们利用NGS技术、独特的标签系统和原始的硅分析管道来开发和内部验证一种新的高通量方法，该方法能够特异性分离HTLV-1整合位点，并准确测量来自各种临床样品的克隆的绝对大小，甚至是那些pvl非常低的样品[Firouzi等]。基因组医学[2014]。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克隆模式特异性的无症状携带者（ACs）和ATL的不同亚型。因此，我们提出htlv -1感染者可以根据其克隆模式分为不同的组，最终影响他们的诊断和治疗选择。此外，在队列研究中，我们监测了罕见的顺序临床样本集，包括临床状态没有变化的样本，临床状态进展到更高级的样本，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检测ATL发病的有益预后指标。总之，实现我们的方法的潜在应用可能对感染个体的诊断、预后和临床治疗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组成。

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.