Bioinformatics Analysis of Next Generation Sequencing Data from Cancer Cells

癌细胞下一代测序数据的生物信息学分析

• 批准号: 10731590
• 负责人: Elizabeth Thomas Bartom
• 金额: $ 22.98万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731590
• 关键词: Acquired Immunodeficiency Syndrome; Area; Award; Base Sequence; Big Data; Bioinformatics; Biological Assay; Biology; Cancer Center; Cancer Patient; Cancer Research Project; Cell Culture Techniques; Cell physiology; Center Core Grants; Chromatin; Comprehensive Cancer Center; Computer Analysis; Data; Data Science Core; Data Set; Defect; Development; Epigenetic Process; Functional disorder; Funding; Gene Activation; Genetic Transcription; Goals; Grant; Human; Human Herpesvirus 8; Investigation; Kaposi Sarcoma; Malignant Neoplasms; Mutation; Patients; Pharmacologic Substance; Regulation; Reproducibility; Research; Research Personnel; Role; Toxic effect; Transcription Elongation; Universities; Work; cancer cell; high standard; improved outcome; insight; member; molecular dynamics; next generation sequencing; programs

Project Summary This proposal is a renewal of a prior R50 grant that supported the bioinformatics needs of cancer researchers at Northwestern University. The initial award primarily supported two NCI funded Outstanding Investigators, Dr. Marcus Peter and Dr. Ali Shilatifard, with a small fraction of support for the Robert H. Lurie Comprehensive Cancer Center. Now, Dr. Bartom has become the Scientific Associate Director for Bioinformatics for the Cancer Center, and she will support a broader array of research programs for different cancer center members. The Unit Director for this proposal is Dr. Leon Platanias, PI of the Cancer Center. A specific area of note will continue to be Dr. Marcus Peter’s investigations into the role of 6mer seed toxicity in the body’s natural defenses against cancer, and how this mechanism can be activated in order to improve outcomes for cancer patients. She will also continue to work with colleagues within the Simpson Querrey Center for Epigenetics, including Dr. Ali Shilatifard, to understand how genetic changes in the machinery of chromatin regulation can lead to epigenetic mutations and defects in gene activation and transcriptional elongation. Research into the molecular dynamics in primary human cell cultures infected with Kaposi’s Sarcoma-associated Herpesvirus will continue with Dr. Eva Gottwein, giving insight into how Kaposi’s Sarcomas arise in AIDS patients. All three of these investigators are cancer center members, whose research is supported by the Cancer Center P30 grant. The common thread in all of these projects is the need for careful, biologically motivated computational analysis to make sense of next generation sequencing data that is essential in examining the function of cells, both before and after cancer development and before and after pharmaceutical perturbation. Dr. Bartom will provide this analysis, and her expertise in both biology and computation will allow cancer biologists to extract more insight from their data, and to maintain a high standard of scientific rigor and reproducibility.

项目摘要 这项提案是对先前支持癌症生物信息学需求的R50拨款的更新 西北大学的研究人员。最初的奖励主要支持NCI资助的两个 杰出的研究人员，马库斯·彼得博士和阿里·希拉蒂法德博士，以一小部分支持 罗伯特·H·卢里综合癌症中心。现在，Bartom博士已经成为科学助理 癌症中心生物信息学主任，她将支持更广泛的研究 针对不同癌症中心成员的计划。这项提议的单位主任是Leon Platanias博士， 癌症中心的派。值得注意的一个具体领域是马库斯·彼得博士对 6聚体种子毒性在人体对癌症的自然防御中的作用，以及这一机制是如何 可以被激活，以改善癌症患者的预后。她还将继续与 Simpson Querrey表观遗传学中心的同事，包括Ali Shilatifard博士，来理解 染色质调节机制中的基因变化如何导致表观遗传突变和 基因激活和转录延长存在缺陷。中国的分子动力学研究 感染卡波西肉瘤相关疱疹病毒的原代人类细胞培养将继续 Eva Gottwein博士介绍了卡波西肉瘤是如何在艾滋病患者身上发生的。这三个都是 研究人员是癌症中心的成员，他们的研究得到了癌症中心P30拨款的支持。 所有这些项目的共同主线是需要仔细的、生物激励的计算 对下一代测序数据进行分析，这是检查功能所必需的 细胞，包括癌症发展前后和药物干扰前后。Dr。 Bartom将提供这项分析，她在生物学和计算方面的专业知识将使癌症 生物学家从他们的数据中提取更多的洞察力，并保持高标准的科学严谨和 再现性。

项目成果

Therapeutic targeting of metabolic vulnerabilities in cancers with MLL3/4-COMPASS epigenetic regulator mutations.

• DOI: 10.1172/jci169993
• 发表时间: 2023-07-03
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Zhao, Zibo;Cao, Kaixiang;Watanabe, Jun;Philips, Cassandra N.;Zeidner, Jacob M.;Ishi, Yukitomo;Wang, Qixuan;Gold, Sarah R.;Junkins, Katherine;Bartom, Elizabeth T.;Yue, Feng;Chandel, Navdeep S.;Hashizume, Rintaro;Ben-Sahra, Issam;Shilatifard, Ali
• 通讯作者: Shilatifard, Ali

Epigenomic landscape and 3D genome structure in pediatric high-grade glioma.

• DOI: 10.1126/sciadv.abg4126
• 发表时间: 2021-06
• 期刊: Science advances
• 影响因子: 13.6

Nore1 inhibits age-associated myeloid lineage skewing and clonal hematopoiesis but facilitates termination of emergency (stress) granulopoiesis.

• DOI: 10.1016/j.jbc.2023.104867
• 发表时间: 2023-07
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Williams, Olatundun;Hu, Liping;Huang, Weiqi;Patel, Priyam;Bartom, Elizabeth T.;Bei, Ling;Hjort, Elizabeth;Hijiya, Christina;Eklund, Elizabeth A.
• 通讯作者: Eklund, Elizabeth A.

Modeling Therapy-Driven Evolution of Glioblastoma with Patient-Derived Xenografts.

• DOI: 10.3390/cancers14225494
• 发表时间: 2022-11-09
• 期刊: Cancers
• 影响因子: 5.2
• 作者: McCord M;Bartom E;Burdett K;Baran A;Eckerdt FD;Balyasnikova IV;McCortney K;Sears T;Cheng SY;Sarkaria JN;Stupp R;Heimberger AB;Ahmed A;James CD;Horbinski C
• 通讯作者: Horbinski C

Effects of H3.3G34V mutation on genomic H3K36 and H3K27 methylation patterns in isogenic pediatric glioma cells.

• DOI: 10.1186/s40478-020-01092-4
• 发表时间: 2020-12-07
• 期刊: Acta neuropathologica communications
• 影响因子: 7.1
• 作者: Huang TY;Piunti A;Qi J;Morgan M;Bartom E;Shilatifard A;Saratsis AM
• 通讯作者: Saratsis AM