Functional Annotations for the Pneumocystis Genome.

肺孢子虫基因组的功能注释。

• 批准号: 6696106
• 负责人: JAREK MELLER
• 金额: $ 18.82万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6696106
• 关键词: Pneumocystis; fungal genetics; gene expression; genetic library; genome; information systems; introns; method development

DESCRIPTION (provided by applicant): A Pneumocystis Genome Project was funded in 1999 with the goals of creating a physical map, an EST database and the assembled DNA sequence for the fungal pathogen, Pneumocystis carinii (Pc). Pc causes one of the major HIV-associated infections, Pneumocystis pneumonia (PcP). The genomic sequencing of Pc is ongoing: large contiguous stretches of several chromosomes as well as a non-redundant set of -1900 EST's are available for analysis. Strategies for gene finding in Pc and further annotation of gene products need to be developed now to fully utilize the growing body of sequence data. In this complementary project, we propose (in accord with specific goals of PAS-02-046) to develop and apply computational tools for gene prediction and annotation for the Pc genome in order to facilitate the search for novel drug targets and potential drug candidates for PcP. Despite the growing number of fungal genomes that are being sequenced, only few gene prediction programs for fungi have been developed. Due to specific biases in A/T content, intron/exon boundaries, promoter sequences and gene densities as well as large differences in organization and structure between different fungal genomes, a training set of well characterized genes and splicing signals needs to be developed for each distinct genome. Moreover, the applicability of splicing alignments that are commonly used to enhance ab initio gene predictions is limited due to the high percentage of genes that do not share similarity with sequences of known genes. Approximately half of the putative Pc genes have no identified orthologs (a situation similar to other fungi, such as yeast and Neurospora). Therefore, gene finding and annotation in Pc as well as in other fungal genomes represent a significant challenge. In the present proposal, as a first step toward full annotation, software and analysis tools will be developed to identify putative genes in the Pc genome. We will take advantage of the EST database, available genomic sequences, known Pc genes, as well as the expertise of the personnel on this proposal to create an integrated biological-computational strategy for gene finding and annotation in Pc. Our specific aims are: 1) To build a representative Pc gene database that will identify intron/exon boundaries and other relevant signals; 2) To develop and train Pc-specific gene recognition methods using hierarchical strategy that combines in a novel way advanced pattern recognition approaches such as Support Vector Machines, Hidden Markov Models and adaptable Neural Networks.

描述（由申请人提供）： 1999年为肺炎囊体基因组项目提供了创建物理图，EST数据库和真菌病原体肺炎刺激性Carinii（PC）的组装DNA序列的目标。 PC引起主要的HIV相关感染之一，肺炎肺炎（PCP）。 PC的基因组测序正在进行中：几个染色体的大连续伸展以及一组非冗余的-1900 EST集可以进行分析。现在需要开发PC中基因查找的策略和基因产物的进一步注释，以充分利用序列数据的不断增长。在这个互补项目中，我们建议（符合PAS-02-046的特定目标），以开发和应用计算工具，以用于PC基因组的基因预测和注释，以促进寻找新的药物靶标和PCP的潜在药物候选者。尽管正在测序的真菌基因组数量越来越多，但仅开发了少数针对真菌的基因预测程序。由于A/T含量，内含子/外显子边界，启动子序列和基因密度以及不同真菌基因组之间组织和结构的巨大差异，因此需要为每个独特的基因组开发一组良好特征的基因和剪接信号。此外，由于与已知基因序列不具有相似性的基因的高百分比，通常用于增强基因预测的剪接比对的适用性受到限制。大约一半的推定PC基因没有鉴定的直系同源物（类似于其他真菌，例如酵母和神经孢子）。因此，PC以及其他真菌基因组中的基因发现和注释是一个重大挑战。在本提案中，作为迈向全面注释的第一步，将开发软件和分析工具，以识别PC基因组中的推定基因。我们将利用EST数据库，可用的基因组序列，已知的PC基因，以及该提案中人员的专业知识，以创建PC中基因查找和注释的综合生物计算策略。我们的具体目的是：1）构建一个代表性的PC基因数据库，该数据库将识别内含子/外显子边界和其他相关信号； 2）使用分层策略开发和训练PC特异性基因识别方法，该方法以新颖的方式结合了高级模式识别方法，例如支持向量机器，隐藏的Markov模型和适应性的神经网络。