Error-pooling-based statistical methods for identifying novel temporal replication profiles of human chromosomes observed by DNA tiling arrays.
Error-pooling-based statistical methods for identifying novel temporal replication profiles of human chromosomes observed by DNA tiling arrays.
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DOI：
10.1093/nar/gkm130
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发表时间：
2007
影响因子：
14.9
通讯作者：
Lee JK
中科院分区：
文献类型：
--
作者：
Park T;Kim Y;Bekiranov S;Lee JK
平铺阵列数据的统计分析是非常具有挑战性的，由于天文数字的序列探针，高噪声水平的个别探针和有限的重复在这些数据。为了克服这些困难，我们首先开发了统计误差估计和加权方差分析建模方法的高密度平铺阵列数据，特别是前者基于一个先进的错误池方法，以准确地获得异质技术误差的小样本平铺阵列数据。基于这些方法，我们分析了高密度平铺阵列数据的时间复制模式在细胞周期S期同步的HeLa细胞在人类21号和22号染色体。我们发现了许多新的时间复制模式，确定约26%的超过100万平铺阵列序列探针在4个2小时的时间段的S期具有显着的差异复制。在这些差异复制探针中，126 941个序列探针与417个已知基因匹配。这些基因中的大多数被发现在一个或两个连续的时间段内复制，而其他的则在两个非连续的时间段内复制。此外，发现编码区在特定的时间段比非编码区在基因贫乏的21号染色体（25%的基因探针之间的差异复制与18.6%之间的基因间探针），而这种现象是不太突出的基因丰富的22号染色体。对差异复制基因和基因间探针的局部接近性进行严格的统计学检验，以鉴定差异复制序列区域的显著延伸。从这个分析中，我们发现相邻的基因在不同的时间段频繁复制，这可能意味着存在相当密集的复制起点。通过对21号和22号染色体上已识别基因的条件概率显著性进行评估，我们发现这些差异复制基因中存在一些过度表达的分子功能和生物学过程，例如与水解酶、转移酶和受体结合活性相关的基因。这些结果中的一些被证实，显示出与平行于平铺阵列独立产生的cDNA微阵列数据> 70%的一致性。因此，我们专门为高密度平铺阵列数据设计的改进分析方法使我们能够可靠和灵敏地识别人类染色体上许多新的时间复制模式。
Statistical analysis on tiling array data is extremely challenging due to the astronomically large number of sequence probes, high noise levels of individual probes and limited number of replicates in these data. To overcome these difficulties, we first developed statistical error estimation and weighted ANOVA modeling approaches to high-density tiling array data, especially the former based on an advanced error-pooling method to accurately obtain heterogeneous technical error of small-sample tiling array data. Based on these approaches, we analyzed the high-density tiling array data of the temporal replication patterns during cell-cycle S phase of synchronized HeLa cells on human chromosomes 21 and 22. We found many novel temporal replication patterns, identifying about 26% of over 1 million tiling array sequence probes with significant differential replication during the four 2-h time periods of S phase. Among these differentially replicated probes, 126 941 sequence probes were matched to 417 known genes. The majority of these genes were found to be replicated within one or two consecutive time periods, while the others were replicated at two non-consecutive time periods. Also, coding regions found to be more differentially replicated in particular time periods than noncoding regions in the gene-poor chromosome 21 (25% differentially replicated among genic probes versus 18.6% among intergenic probes), while such a phenomenon was less prominent in gene-rich chromosome 22. A rigorous statistical testing for local proximity of differentially replicated genic and intergenic probes was performed to identify significant stretches of differentially replicated sequence regions. From this analysis, we found that adjacent genes were frequently replicated at different time periods, potentially implying the existence of quite dense replication origins. Evaluating the conditional probability significance of identified gene ontology terms on chromosomes 21 and 22, we detected some over-represented molecular functions and biological processes among these differentially replicated genes, such as the ones relevant to hydrolase, transferase and receptor-binding activities. Some of these results were confirmed showing >70% consistency with cDNA microarray data that were independently generated in parallel with the tiling arrays. Thus, our improved analysis approaches specifically designed for high-density tiling array data enabled us to reliably and sensitively identify many novel temporal replication patterns on human chromosomes.
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影响因子：
3
作者：
Dean N;Raftery AE
通讯作者：
Raftery AE
DOI：
10.1073/pnas.0405088102
发表时间：
2005-05-03
影响因子：
11.1
作者：
Jeon, Y;Bekiranov, S;Dutta, A
通讯作者：
Dutta, A
影响因子：
7
作者：
Kampa, D;Cheng, J;Gingeras, TR
通讯作者：
Gingeras, TR
影响因子：
5.8
作者：
Beissbarth, T;Speed, TP
通讯作者：
Speed, TP
DOI：
10.1073/pnas.1530509100
发表时间：
2003-08-05
影响因子：
11.1
作者：
Storey, JD;Tibshirani, R
通讯作者：
Tibshirani, R