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標題: | 比較24位點MIRU-VNTR與全基因定序兩種基因分型方法所辨別的結核病群聚一致性:以醫院為基礎的研究 Comparing the consistency of 24-loci MIRU-VNTR and whole genome sequencing in identifying clusters: a hospital-based study in Taiwan |
作者: | Yu-Ren Liao 廖佑荏 |
指導教授: | 林先和(Hsien-Ho Lin) |
關鍵字: | 結核病,基因分型,全基因定序,結核分枝桿菌散置變異性重複序列, Tuberculosis,genotyping,whole genome sequencing,mycobacterial interspersed repetitive-unit-variable-number tandem-repeat, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 背景
由於結核病透過空氣傳播,以致難以明確釐清傳染源。然而,結核分枝桿菌散置變異性重複序列及全基因定序兩種基因分型方法能夠區分不同群聚事件,輔以克服該困境。本研究目的將比較兩種基因分型方法,探討他們在根據在地數據資料下的一致性。 方法 在2017年3月至12月期間,來自高雄醫學大學體系內四家醫院的結核病患者(n = 155),均透過痰培養確認且具有完整的流行病學數據,包括基因數據。對這些患者的分離株採用國際標準24位點結核分枝桿菌散置變異性重複序列及全基因定序分型方法進行分析,對於每對病人的分離株,具有相同的結核分枝桿菌散置變異性重複序列表現譜定義為「結核分枝桿菌散置變異性重複序列群聚」,具有≤12的單核苷酸多態性距離則被定義為「全基因定序群聚」。流行病學資訊包括結核病例之間的已知接觸紀錄,以及每位患者的居住、戶籍和工作地址。我們分析結核分枝桿菌散置變異性重複序列和全基因定序兩者之間群聚的一致性,同時檢驗它們判別的群聚與流行病學數據之間是否具有相關性,若接觸調查支持其關係,抑或是病人間地理距離相距5公里內,均判別為有流病關聯性。 結果 隨著結核分枝桿菌散置變異性重複序列上基因位點差異數量增加,單核苷酸多態性距離也增加。在具有相同24位點結核分枝桿菌散置變異性重複序列的88對患者中,只有8對(9.1%)的單核苷酸多態性距離≤12。另外,在單核苷酸多態性距離≤12的23對患者中,有15對(65.2%)在結核分枝桿菌散置變異性重複序列模式中至少有一個位點的差異。 23對全基因定序有關的群聚中有13對(57%)具有地理相關性,而88對(29.5%)結核分枝桿菌散置變異性重複序列有關的群聚,只有26對是地理相關性。值得注意的是,我們的全基因定序分析顯示了有四個潛在的基因型群聚存在,但其中僅有一個是通過常規接觸調查確定。 結論 在我們的研究人群中,24位點結核分枝桿菌散置變異性重複序列和全基因定序分析的分析結果顯示兩工具分型存在不一致的情形,又以結核分枝桿菌散置變異性重複序列的群聚不一致情況最嚴重。透過接觸調查和地理空間資訊結果表現出全基因定序的群聚比結核分枝桿菌散置變異性重複序列群聚更具有流病相關性。 Introduction Due to Tuberculosis (TB) transmissible characteristic of airborne, it is difficult to clarify the source of infection. However, whole genome sequencing (WGS) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VTNR) of genotyping techniques can identify separate clusters as different transmission events to overcome this obstacle. The purpose of this study is to compare two genotyping methods head-to-head, and to explore the consistency of them based on local epidemiological data. Methods Between March and December 2017, TB patients (n = 155) from four hospitals of the Kaohsiung Medical University system were confirmed by sputum culture and had complete epidemiological data, including genetic data. The isolates of these patients were employed both international standard 24-loci MIRU-VNTR and WGS. For each pair of patients, the same MIRU-VNTR pattern was defined as 'MIRU-VNTR cluster', and the single nucleotide polymorphism (SNP) distance of ≤ 12 was defined as 'WGS cluster'. Epidemiological information included known contact investigation between TB cases, and the location of patients such as permanent, residential, and work addresses. We analyzed the concordance of clusters between MIRU-VNTR and WGS, and examined whether there was a correlation between genetic clusters and epidemiological data. If contact investigation had shown to support the relationship between the pair, or the geographical distance between patients within 5 kilometer (km), the pair were identified as having epidemiological correlation. Results The SNP distance increased as the number of discrepant MIRU loci increased. Among the 88 pairs of patients with identical 24-MIRU pattern, only eight (9.1%) pairs had a SNP distance of ≤12. On the other hand, among the 23 pairs of patients with SNP ≤12, 15 pairs (65.2%) had at least one loci difference in MIRU pattern. 13 of 23 (57%) WGS-linked pairs had geographical correlation, while only 26 of 88 (29.5%) MIRU linked pairs were geographical correlation. Of note, our WGS analysis revealed four potential genotypic clusters, but only one of them had been identified by conventional contact investigation. Conclusion In our study population, the outcomes of 24-loci MIRU-VNTR and WGS had indicated that there was high discordant situation between two genotyping tools, especially for MIRU-VNTR clusters. Through contact investigation and spatial information, WGS clusters were more epidemiological correlation than MIRU-VNTR. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78622 |
DOI: | 10.6342/NTU201901899 |
全文授權: | 有償授權 |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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