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）： 肺孢子虫基因组计划于 1999 年获得资助，目标是创建真菌病原体卡氏肺孢子虫 (Pc) 的物理图谱、EST 数据库和组装的 DNA 序列。 PC 会导致一种主要的 HIV 相关感染，即肺孢子菌肺炎 (PcP)。 Pc 的基因组测序正在进行中：几条染色体的大片连续延伸以及一组非冗余的 -1900 EST 可用于分析。现在需要制定在电脑中寻找基因和进一步注释基因产物的策略，以充分利用不断增长的序列数据。在这个补充项目中，我们建议（根据PAS-02-046的具体目标）开发和应用PC基因组基因预测和注释的计算工具，以促进寻找新的药物靶点和潜在的候选药物五氯苯酚。尽管正在测序的真菌基因组数量不断增加，但仅开发了很少的真菌基因预测程序。由于A/T含量、内含子/外显子边界、启动子序列和基因密度的特定偏差以及不同真菌基因组之间的组织和结构的巨大差异，需要为每个真菌开发一组明确表征的基因和剪接信号的训练集独特的基因组。此外，由于与已知基因的序列不具有相似性的基因的比例很高，通常用于增强从头开始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 基因没有确定的直系同源物（与其他真菌类似的情况，例如酵母和脉孢菌）。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，作为全面注释的第一步，将开发软件和分析工具来识别 PC 基因组中的假定基因。我们将利用 EST 数据库、可用的基因组序列、已知的 PC 基因以及该提案人员的专业知识，为 PC 中的基因查找和注释创建集成的生物计算策略。我们的具体目标是： 1）建立一个具有代表性的PC基因数据库，用于识别内含子/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 特定的基因识别方法，该策略以新颖的方式结合先进的模式识别方法，如支持向量机、隐马尔可夫模型和自适应神经网络。