Gene and alternative splicing annotation with AIR
Gene and alternative splicing annotation with AIR
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DOI：
10.1101/gr.2889405
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发表时间：
2005-01-01
期刊：
影响因子：
7
通讯作者：
Sutton, G
中科院分区：
文献类型：
--
作者：
Florea, L;Di Francesco, V;Sutton, G
由于数据的不完整和不准确、计算模型的局限性以及基因组学中不断变化的范式（如可变剪接），设计有效且准确的工具来识别基因组中的功能和结构元件仍然处于基因组注释的前沿。我们提出了一种基于来自同一物种的现有cDNA和蛋白质序列证据，或使用同线性映射信息从相关物种推断的基因及其可变剪接mRNA转录本的自动注释方法。该方法的核心是剪接图，它是基因、其外显子、内含子和可变剪接异构体的一种紧凑表示形式。从图中列举出假定的转录本，并根据序列证据的强度赋予置信分数，然后选择高分候选者的一个子集并将其纳入注释。该方法具有高度选择性，在去除不太可能的候选者的同时，能将98%的高质量mRNA证据保留在结构良好的转录本中，并且所产生的注释比一些基于证据的基因集明显更准确。这个过程快速、准确且完全自动化，以一种全面且系统的方式将传统上不同的基因注释和可变剪接检测过程结合起来，从而极大地有助于后续的人工校正工作。
Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. We present a methodology for the automated annotation of genes and their alternatively spliced mRNA transcripts based on existing cDNA and protein sequence evidence from the same species or projected from a related species using syntenic mapping information. At the core of the method is the splice graph, a compact representation of a gene, its exons, introns, and alternatively spliced isoforms. The putative transcripts are enumerated from the graph and assigned confidence scores based on the strength of sequence evidence, and a subset of the high-scoring candidates are selected and promoted into the annotation. The method is highly selective, eliminating the unlikely candidates while retaining 98% of the high-quality mRNA evidence in well-formed transcripts, and produces annotation that is measurably more accurate than some evidence-based gene sets. The process is fast, accurate, and fully automated, and combines the traditionally distinct gene annotation and alternative splicing detection processes in a comprehensive and systematic way, thus considerably aiding in the ensuing manual curation efforts.