A novel unsupervised method to identify genes important in the anti-viral response: application to interferon/ribavirin in hepatitis C patients.
A novel unsupervised method to identify genes important in the anti-viral response: application to interferon/ribavirin in hepatitis C patients.
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DOI：
10.1371/journal.pone.0000584
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发表时间：
2007-07-04
期刊：
影响因子：
3.7
通讯作者：
Taylor MW
中科院分区：
文献类型：
--
作者：
Brodsky LI;Wahed AS;Li J;Tavis JE;Tsukahara T;Taylor MW
用干扰素/利巴韦林治疗丙型肝炎在病毒滴度降低和最终结果方面的反应各不相同。显著应答者在治疗开始的几天内病毒滴度急剧下降，而在其他患者中对病毒没有影响（不良应答者）。先前的研究表明，联合治疗在体外和体内改变了数百个基因的表达。然而，确定这些基因中的哪些（如果有的话）在病毒清除中起作用仍然具有挑战性。本文的目的是将病毒水平与基因表达联系起来，从而确定可能导致病毒滴度早期下降的基因。对从接受干扰素/利巴韦林治疗的患者的PBMC分离的RNA进行微阵列。在给药前（第0天）和开始给药后1、2、7、14和28天采集样本。应用一种新的方法来鉴定与干扰素/利巴韦林治疗期间病毒滴度降低相关的基因。该方法使用基于患者间基因表达的接近度和基于患者间病毒滴度的接近度之间的关系来定义每个基因的微阵列基因表达测量值和病毒滴度测量值之间的关联。我们检测到36个独特的基因，其表达提供了类似于基于病毒滴度的患者聚类的患者聚类。这些基因包括IRF 7、MX 1、OASL和OAS 2、viperin和许多功能未知的ISG。通过这种方法鉴定的基因似乎在治疗的早期阶段减少丙型肝炎病毒中起主要作用。该方法具有广泛的实用性，并可用于分析响应于任何组的影响生物学结果的因素，如抗病毒药物或抗癌剂，其中微阵列数据是可用的。
Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available.
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影响因子：
5.3
作者：
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通讯作者：
Crocker, PR
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2.1
作者：
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作者：
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DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D