Gene structure prediction and alternative splicing analysis using genomically aligned ESTs
Gene structure prediction and alternative splicing analysis using genomically aligned ESTs
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DOI：
10.1101/gr.155001
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发表时间：
2001-05-01
期刊：
影响因子：
7
通讯作者：
States, DJ
中科院分区：
文献类型：
--
作者：
Kan, ZY;Rouchka, EC;States, DJ
随着人类基因组几乎完整的序列的可用性，对基因组序列的表达序列标签（EST）已成为基因预测的实用且强大的策略。阐明基因结构是一个复杂的问题，需要识别剪接连接，基因边界和替代剪接变体。我们已经开发了一种软件工具，即成绩单组装程序（TAP），以使用基因组对齐的EST序列来描述基因结构。 TAP使用单个剪接连接对的整个基因组区域的关节基因结构，使用一种新型算法，该算法使用EST编码的连接性和冗余信息来整理复杂的替代剪接模式。已经开发了一种称为聚腺苷酸化位点扫描（PASS）的方法来检测基因组中的聚-A位点。 TAP使用这些预测来通过分割聚腺苷酸化末端外显子的关节基因结构来识别基因边界。重建1007个已知成绩单，TAP在外显子水平上评分为60％的灵敏度（SN），特异性（SP）为92％。发现基因边界识别过程是准确的78％。 TAP还报告EST对齐中的替代剪接模式。对1124个基因区域中替代剪接的分析表明，超过一半的人类基因经历了替代剪接。令人惊讶的是，我们看到绝对大多数检测到的替代剪接事件会影响编码区域。此外，使用基于EST的方法分析了人与小鼠之间替代剪接的进化保守。 （请参阅http://stl.wustl.edu/-zkan/tap/）。
With the availability of a nearly complete sequence of the human genome, aligning expressed sequence tags (EST) to the genomic sequence has become a practical and powerful strategy for gene prediction. Elucidating gene structure is a complex problem requiring the identification of splice junctions, gene boundaries, and alternative splicing variants. We have developed a software tool, Transcript Assembly Program (TAP), to delineate gene structures using genomically aligned EST sequences. TAP assembles the joint gene structure of the entire genomic region from individual splice junction pairs, using a novel algorithm that uses the EST-encoded connectivity and redundancy information to sort out the complex alternative splicing patterns. A method called polyadenylation site scan (PASS) has been developed to detect poly-A sites in the genome. TAP uses these predictions to identify gene boundaries by segmenting the joint gene structure at polyadenylated terminal exons. Reconstructing 1007 known transcripts, TAP scored a sensitivity (Sn) of 60% and a specificity (Sp) of 92% at the exon level. The gene boundary identification process was found to be accurate 78% of the time. TAP also reports alternative splicing patterns in EST alignments. An analysis of alternative splicing in 1124 genic regions suggested that more than half of human genes undergo alternative splicing. Surprisingly, we saw an absolute majority of the detected alternative splicing events affect the coding region. Furthermore, the evolutionary conservation of alternative splicing between human and mouse was analyzed using an EST-based approach. (See http://stl.wustl.edu/-zkan/TAP/).