GENE PREDICTION--MARKOV MODELS AND COMPLEMENTARY METHODS

描述(改编自《调查者摘要》)：项目目标 是建立更准确和更强大的DNA序列解释算法 利用先前证明的GeneMark和 GenMark.HMM方法。 我们计划在以下方面提高在原核基因组中发现基因的质量 可靠和准确的基因起始预测和移码检测 测序错误。我们还计划开发一个机器学习迭代 推导精确基因的所有必要模型的步骤 从完全匿名的原核序列进行预测/注释。 对于真核物种，我们将提高从头算方法的准确性。 通过构建更准确的剪接位点模型和 启动/终止地点，我们将准确地解决 寻找具有多聚腺苷酸化位点和启动子的基因间隔区。 在GeneMark.HMM的基础上，我们计划开发一种集成的基因发现 方法是将不同的外在证据“投射”到DNA水平， 将它们翻译成DNA模式，并将这些模式与 广义DNA编码序列和非编码序列的统计模式 嗯，模特。这些附加信息最耐人寻味的来源是 近缘物种DNA序列中的进化保守区， 蛋白质序列中的功能基序和反映蛋白质序列模式 三维结构主题。 所有这些新开发的方法，以及 提案，将处理匿名DNA，对其的解释越来越多 是后基因组时代所需要的。

DESCRIPTION (Adapted from the Investigator's Abstract): The goal of the project is to build more accurate and powerful DNA sequence interpretation algorithms utilizing the positive experience and ideas of previously proven GeneMark and GenMark.hmm methods. We plan to improve the quality of gene finding in prokaryotic genomes in terms of reliable and accurate prediction of gene starts and detection of frameshift sequencing errors. We also plan to develop a machine-learning iterative procedure for deriving all necessary models for precise gene prediction/annotation from totally anonymous prokaryotic sequences. For eukaryotic species, we will improve the accuracy of the ab initio method GeneMark.hmm by building more accurate models for splice sites and initiation/termination sites, and we will address the problem of accurately finding intergenic regions with polyadenilation sites and promoters. On the basis of GeneMark.hmm, we plan to develop an integrated gene finding approach by "projecting" pieces of diverse extrinsic evidence into DNA level, the translating them into DNA patterns and combining these patterns with statistical patterns of DNA coding and non-coding sequence within a generalized HMM model. The most intriguing sources of this additional information are evolutionary conserved regions in DNA sequences of closely related species, functional motifs in protein sequences and protein sequence patterns reflecting three dimensional structural motifs. All these newly developed methods, as well as several others mentioned in the proposal, will deal with anonymous DNA for which interpretation is increasingly needed in the post-genomic era.