Modeling leaderless transcription and atypical genes results in more accurate gene prediction in prokaryotes.

Modeling leaderless transcription and atypical genes results in more accurate gene prediction in prokaryotes.
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DOI:
10.1101/gr.230615.117
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发表时间:
2018-07
期刊:
影响因子:
7
通讯作者:
Borodovsky M
Borodovsky M
中科院分区:
生物学1区
文献类型:
--
作者:
Lomsadze A;Gemayel K;Tang S;Borodovsky M

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在原核基因组组织的传统观点中,启动子先于操纵子和核糖体结合位点(RBS),而Shine-Dalgarno共有序列先于基因。然而,最近的实验研究表明更加多样化的观点促使我们开发一种提高基因查找准确性的算法。我们描述了 GeneMarkS-2,这是一种从头开始的算法,它使用通过自我训练得出的模型来寻找物种特异性(天然)基因,以及一系列预先计算的“启发式”模型,旨在识别难以检测的基因(可能是水平转移的)。重要的是,我们设计 GeneMarkS-2 来识别参与基因表达控制的几种不同类型的序列模式(信号),其中包括无前导序列转录的特征模式以及非规范 RBS 模式。为了评估 GeneMarkS-2 的准确性,我们使用了通过 COG(直系同源簇)注释、蛋白质组学实验和 N 端蛋白质测序验证的基因。我们观察到,与当前最先进的基因预测工具相比,GeneMarkS-2 在所有准确度测量中平均表现更好。此外,GeneMarkS-2 对约 5000 个代表性原核基因组的筛选预测了古细菌和细菌中频繁出现的无前导序列转录。我们还观察到,一些具有先导转录的物种中的 RBS 位点不一定表现出 Shine-Dalgarno 共识。调节基因表达的不同类型序列基序的建模促使原核基因组分为五类,在基因起始点周围具有不同的序列模式。
In a conventional view of the prokaryotic genome organization, promoters precede operons and ribosome binding sites (RBSs) with Shine-Dalgarno consensus precede genes. However, recent experimental research suggesting a more diverse view motivated us to develop an algorithm with improved gene-finding accuracy. We describe GeneMarkS-2, an ab initio algorithm that uses a model derived by self-training for finding species-specific (native) genes, along with an array of precomputed “heuristic” models designed to identify harder-to-detect genes (likely horizontally transferred). Importantly, we designed GeneMarkS-2 to identify several types of distinct sequence patterns (signals) involved in gene expression control, among them the patterns characteristic for leaderless transcription as well as noncanonical RBS patterns. To assess the accuracy of GeneMarkS-2, we used genes validated by COG (Clusters of Orthologous Groups) annotation, proteomics experiments, and N-terminal protein sequencing. We observed that GeneMarkS-2 performed better on average in all accuracy measures when compared with the current state-of-the-art gene prediction tools. Furthermore, the screening of ∼5000 representative prokaryotic genomes made by GeneMarkS-2 predicted frequent leaderless transcription in both archaea and bacteria. We also observed that the RBS sites in some species with leadered transcription did not necessarily exhibit the Shine-Dalgarno consensus. The modeling of different types of sequence motifs regulating gene expression prompted a division of prokaryotic genomes into five categories with distinct sequence patterns around the gene starts.
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