Functional Annotations for the Pneumocystis Genome.

肺孢子虫基因组的功能注释。

• 批准号: 6782669
• 负责人: JAREK MELLER
• 金额: $ 17.45万
• 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 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6782669
• 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年资助了一个肺孢子虫基因组计划，目标是建立一个物理图谱、一个EST数据库和一个真菌病原体卡氏肺孢子虫（Pc）的DNA序列。Pc导致主要的HIV相关感染之一，肺孢子虫肺炎（PcP）。Pc的基因组测序正在进行中：几条染色体的大的连续延伸以及约1900个EST的非冗余集合可用于分析。现在需要开发在Pc中发现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（在雅阁PAS-02-046的具体目标）开发和应用计算工具的基因预测和注释的Pc基因组，以促进寻找新的药物靶点和潜在的药物候选人的PcP。尽管越来越多的真菌基因组被测序，只有少数真菌的基因预测程序已经开发出来。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组织和结构的巨大差异，需要为每个不同的基因组开发一组良好表征的基因和剪接信号的训练集。此外，剪接比对的适用性，通常用于增强从头基因预测是有限的，由于高百分比的基因不共享与已知基因的序列的相似性。大约有一半的推定Pc基因没有确定的直系同源物（类似于其他真菌，如酵母和脉孢菌的情况）。因此，在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，作为迈向完整注释的第一步，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，以及该建议的人员的专业知识，以创建一个综合的生物计算策略，基因发现和注释的Pc。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特异性基因识别方法，该策略以一种新的方式结合了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。

项目成果

Draft assembly and annotation of the Pneumocystis carinii genome.

卡氏肺囊虫基因组的组装草图和注释。

• DOI: 10.1111/j.1550-7408.2006.00184.x
• 发表时间: 2006
• 期刊: The Journal of eukaryotic microbiology
• 作者: Slaven,BradleyE;Meller,Jaroslaw;Porollo,Aleksey;Sesterhenn,Thomas;Smulian,AGeorge;Cushion,MelanieT
• 通讯作者: Cushion,MelanieT

Large-scale characterization of introns in the Pneumocystis carinii genome.

卡氏肺囊虫基因组内含子的大规模表征。

• DOI: 10.1111/j.1550-7408.2006.00211.x
• 发表时间: 2006
• 期刊: The Journal of eukaryotic microbiology
• 作者: Slaven,BradleyE;Porollo,Aleksey;Sesterhenn,Thomas;Smulian,AGeorge;Cushion,MelanieT;Meller,Jaroslaw
• 通讯作者: Meller,Jaroslaw