GENES AND PATHWAYS INTERACTING WITH SPHINGOLIPID PATHWAY IN CANCER PATHOGENESIS

癌症发病过程中与鞘脂通路相互作用的基因和通路

• 批准号: 8360385
• 负责人: WENJIN Jim ZHENG
• 金额: $ 9.4万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-07-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360385
• 关键词: Back; Centers of Research Excellence; Computing Methodologies; Fingerprint; Funding; Genes; Genetic Transcription; Genomics; Goals; Grant; Link; Literature; Malignant Neoplasms; Modeling; National Center for Research Resources; Ontology; Pathogenesis; Pathway interactions; Pattern; Play; Principal Investigator; PubMed; Research; Research Infrastructure; Resources; Role; Source; Sphingolipids; Statistical Methods; United States National Institutes of Health; abstracting; base; cancer cell; cost; genome wide association study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Biologically active sphingolipids play key roles in cancer pathogenesis. While the sphingolipid pathway itself has been extensively studied, its interaction with other genes and pathways is poorly understood but is essential for its action in cancer pathogenesis. We have developed the concept of ontology fingerprint  a list of ontology terms overrepresented in the PubMed abstracts linked to a gene or a pathway along with their corresponding enrichment p-value, to characterize genes and pathways. We further identified genes of a pathway by comparing their ontology fingerprints  the more similar the ontology fingerprint between a gene and a pathway, the more likely the gene will play a role in the pathway. Based on this approach, we hypothesize that: 1) genes and pathways interacting with sphingolipid pathway and influencing its role in cancer pathogenesis will share similar ontology fingerprints with sphingolipid pathway and genes; 2) these genes and pathways can be identified by comparing their ontology fingerprint with that of sphingolipid pathway and genes; 3) we can decipher how these genes and pathways interact with sphingolipid pathway by tracing back to the biomedical literatures contributed to their ontology fingerprints; 4) the inferred relationship between genes and pathways can be investigated and validated by checking whether these genes are co-expressed in cancer cells and whether they are located in the loci strongly associated with cancer identified from genome-wide association studies. We will evaluate our hypothesis by evaluating the following specific aims: 1) Identify genes and pathways interacting with sphingolipid pathway by ontology fingerprints and Bayesian model; and 2) Analyze and validate the interplay of identified genes and pathways with sphingolipid pathway by deciphering the functional role of identified genes and pathways in cancer pathogenesis involved in sphingolipid pathway using PubMed literatures, co-expression patterns of identified genes and the association of these genes with genomic loci that are identified to be associated with cancer pathogenesis from Genome Wide Association Studies. Our long term goal is to develop computational and statistical methods to integrate information from biomedical literature, transcription profiling and genome-wide association study to study genes and pathways interacting with sphingolipid pathway and to decipher the role of such interplay in cancer pathogenesis.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 生物活性鞘脂在癌症发病机理中起关键作用。 尽管鞘脂途径本身已经进行了广泛的研究，但其与其他基因和途径的相互作用知之甚少，但对于其在癌症发病机理中的作用至关重要。 我们已经开发了本体学指纹的概念，一个本体术语列表中与基因或途径相关的PubMed摘要及其相应的富集p值的概念，以表征基因和途径。 我们通过比较它们的本体学指纹进一步识别了途径的基因，其本基因和途径之间的本体学指纹越相似，该基因在途径中的作用越大。 基于这种方法，我们假设：1）与鞘脂途径相互作用并影响其在癌症发病机理中的作用的基因和途径将与鞘脂途径和基因共享相似的本体学指纹； 2）可以通过将它们的本体指纹与鞘脂途径和基因的本体学指纹进行比较来识别这些基因和途径； 3）我们可以通过追溯到生物医学文献有助于其本体论指纹来解解这些基因和途径如何与鞘脂途径相互作用； 4）可以通过检查这些基因在癌细胞中共表达的基因与途径之间的推断关系，以及它们是否位于基因座中与从基因组全基因组关联研究中发现的癌症密切相关的基因座。 我们将通过评估以下特定目的来评估我们的假设：1）通过本体学指纹和贝叶斯模型确定与鞘脂途径相互作用的基因和途径；和2）通过解释鉴定基因和鞘脂途径与鞘脂途径的相互作用，通过解释已鉴定基因和途径在鞘脂途径中涉及的癌症发病机理的功能作用，使用PubMed文献，使用PubMed文献，共表达模式的共表达模式，以及这些基因与基因组相关的基因相关的基因相关的基因的关联。 我们的长期目标是开发计算和统计方法，以整合来自生物医学文献，转录分析和全基因组关联研究的信息，以研究与鞘脂途径相互作用的基因和途径，并破译这种相互作用在癌症发病机理中的作用。