Genome-wide analysis of mouse transcripts using exon microarrays and factor graphs

Genome-wide analysis of mouse transcripts using exon microarrays and factor graphs
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DOI:
10.1038/ng1630
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发表时间:
2005-09-01
期刊:
影响因子:
30.8
通讯作者:
Hughes, TR
Hughes, TR
中科院分区:
生物学1区
文献类型:
--
作者:
Frey, BJ;Mohammad, N;Hughes, TR

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最近的哺乳动物微阵列实验检测到广泛的转录,并表明可能存在许多未被发现的多外显子蛋白质编码基因。为了探索这种可能性,我们将来自 37 个小鼠组织的未扩增、多腺苷酸化选择的 RNA 样本中的 cDNA 标记到包含 114 万个外显子探针的微阵列中。我们使用 GenRate 分析了这些数据,GenRate 是一种贝叶斯算法,它使用因子图中的全基因组评分函数来推断基因。 GenRate 以 2.7% 的严格外显子错误检测率检测到 12,145 个基因长度转录本,并确认了 10,000 个表达最高的已知基因中的 81%。值得注意的是,我们的分析表明,GenRate 检测到的 155,839 个外显子中的大多数与已知基因相关,这提供了基于微阵列的证据,表明大多数多外显子基因已被识别。 GenRate 还检测到数以万计的潜在新外显子,并通过将新转录区域“缝合”到先前注释的基因中来协调当前 cDNA 数据库中的差异。
Recent mammalian microarray experiments detected widespread transcription and indicated that there may be many undiscovered multiple- exon protein- coding genes. To explore this possibility, we labeled cDNA from unamplified, polyadenylation- selected RNA samples from 37 mouse tissues to microarrays encompassing 1.14 million exon probes. We analyzed these data using GenRate, a Bayesian algorithm that uses a genome- wide scoring function in a factor graph to infer genes. At a stringent exon false detection rate of 2.7%, GenRate detected 12,145 gene- length transcripts and confirmed 81% of the 10,000 most highly expressed known genes. Notably, our analysis showed that most of the 155,839 exons detected by GenRate were associated with known genes, providing microarray- based evidence that most multiple- exon genes have already been identified. GenRate also detected tens of thousands of potential new exons and reconciled discrepancies in current cDNA databases by ` stitching' new transcribed regions into previously annotated genes.