NHGRI/DIR Bioinformatics and Scientific Programming Core

NHGRI/DIR 生物信息学和科学编程核心

• 批准号: 8750737
• 负责人: Andreas Baxevanis
• 金额: $ 334.41万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8750737
• 关键词: Address; Alternative Splicing; Anemia; Archives; Behavioral; Binding; Binding Sites; Bioinformatics; Biological Markers; Bladder Neoplasm; Canis familiaris; Cataloging; Catalogs; ChIP-seq; Clinical; Clinical Data; Code; Communities; Complementary DNA; Computer Analysis; Computer software; DNA Binding; Data; Data Collection; Databases; Detection; Development; Diagnosis; EP300 gene; Enhancers; Exhibits; Exons; Gene Expression; Genes; Genetic; Genome; Genomics; Genotype; Global Change; Goals; Hereditary Disease; Histocompatibility Testing; Human; Investigation; Lewy Body Dementia; Location; Malignant Neoplasms; Maps; Measurement; Metastatic Melanoma; Methylation; Mnemiopsis; Mus; Mutation; Mutation Detection; National Human Genome Research Institute; Nucleic Acid Regulatory Sequences; Oncogenes; Online Systems; Orthologous Gene; Pathway Analysis; Pathway interactions; Patients; Phenotype; Plant Genome; Protein Isoforms; Proteins; Quality Control; RNA Interference; RNA Splicing; Records; Research; Research Personnel; Research Support; Retrieval; Sampling; Sequence Analysis; Silent Mutation; Site; Solutions; Somatic Mutation; Spliced Genes; Surveys; Techniques; Terminology; Text; The Cancer Genome Atlas; Time; Transcript; Tumor Cell Line; Tumor Subtype; Update; Variant; Weight; Weight maintenance regimen; Woman; Zebrafish; base; computerized tools; design; exome sequencing; genetic pedigree; glucosylceramidase; histone modification; human disease; innovation; invertebrate genome; malformation; malignant breast neoplasm; melanoma; programs; response; thymocyte; tool; transcription factor; transcriptome sequencing; tumor; vertebrate genome; web interface; web site

The NHGRI Bioinformatics and Scientific Programming Core actively supports the research being performed by NHGRI investigators by providing expertise and assistance in bioinformatics and computational analysis. The Core facilitates access to specialized software and hardware, develops generalized software solutions that can address a variety of questions in genomic research, develops database solutions for the efficient archiving and retrieval of experimental and clinical data, disseminates new software and database solutions to the genome community at-large, collaborates with NHGRI researchers on computationally-intensive projects, and provides educational opportunities in bioinformatics to NHGRI Investigators and trainees. Scientific projects completed in 2012-2013 include the valuation of shared motifs in sequences flanking non-Alu driven break point deletions in FANCA and FANCC; the analysis of RNA-seq data to detect global changes in gene expression and splicing due to RRP1B knockdown; the design and implementation of the Clinical Genomic Database (CGD), a searchable, Web-based database of all conditions with known genetic causes; the creation of a comprehensive list of mutations by merging lab-generated genotypes with those in COSMIC (Catalogue of Somatic Mutations in Cancer); quality control and subsequent retrieval of genomic coordinates from HGVS-formatted cDNA and protein mutations; pathway analysis of a list of genes implicated in melanoma by exome sequencing of metastatic melanoma samples; prediction of gene regulatory regions in thymocytes of Itk deficient mice; collation of multi-center survey data to study association between glucocerebrosidase mutations and Lewy Body dementia; and analysis of sequence traces to detection mutations for the zebrafish TILLING project Ongoing scientific projects include the annotation of the Mnemiopsis genome using NextGen sequence data; the detection of gene and isoform expression changes during early development by RNA-seq; the analysis of human disease gene orthologs in Mnemiopsis; the analysis of sequence traces to detect mutations in putative oncogenes in tumor samples; development of a human malformation terminology tool to allow clinicians to build and maintain downloadable spreadsheets of patient conditions; the characterization of large exons in vertebrate, invertebrate, and plant genomes; ongoing updates and improvements to the Breast Cancer Information Core (BIC); the development of a bioinformatic pipeline to map zebrafish retroviral integration sites using Illumina sequence tags and to identify integrations occurring within ENSEMBL-annotated genes; development of a Web site and database to search for integration sites; the analysis of RNA-seq data to investigate alternative splicing in Fanconia Anemia patients; the analysis of alternatively spliced genes in select tissue types over time; the identification of a set of 500 methylation markers that classifies different types of tumors; the identification of DNA binding sites of RRP1B by ChIP-seq; determination of the effects of RRP1B knockdown on gene expression; the development of a customized SQL database for storing and computing on large numbers of records for canine genotypes, phenotypes, sequences, variations, sample data, and pedigree data; the analysis of ChIP-seq data to identify the genomic locations of specific histone modifications in dog bladder tumor cell lines; genome-guided, ab initio, and de novo transcript assembly for RNA-seq data; the analysis of ChIP-seq to investigate Sox10 transcription factor binding at enhancer sites in mouse, and correlating Sox10 binding with EP300 and H3K4Me1 binding; the mapping and annotation of transcription factors to experimental and predicted transcription factor binding sites; the development of a Web-based survey studying how women feel about the techniques doctors use to talk with patients about their weight (Weight Management Interaction Study); identification of co-varying mutations and pathways to classify subtypes of tumors; measurement of gene expression changes in thymocytes over four different stimulations and four different mutations; biomarker selection of targets from RNAi screens; performing multi-species BLAST to estimate cross-species sequence similarity of protein-coding genes; software pipeline to create word cloud based on SMS text responses from visitors as they interact with the Smithsonian genome exhibit; development of a Web interface and data collection for eight surveys developed by SBRB PIs in conjunction with the Smithsonian genome exhibit; and investigation of the effect of silent mutations on splicing from TCGA RNA-seq data.

NHGRI 生物信息学和科学编程核心通过提供生物信息学和计算分析方面的专业知识和帮助，积极支持 NHGRI 研究人员正在进行的研究。该核心促进对专用软件和硬件的访问，开发可以解决基因组研究中的各种问题的通用软件解决方案，开发用于实验和临床数据的高效归档和检索的数据库解决方案，向整个基因组社区传播新的软件和数据库解决方案，与 NHGRI 研究人员合作开展计算密集型项目，并向 NHGRI 提供生物信息学教育机会 调查员和实习生。 2012-2013年完成的科学项目包括评估FANCA和FANCC中非Alu驱动的断点删除侧翼序列中的共享基序；分析 RNA-seq 数据以检测 RRP1B 敲低导致的基因表达和剪接的全局变化；临床基因组数据库（CGD）的设计和实施，这是一个可搜索的、基于网络的数据库，包含已知遗传原因的所有疾病；通过将实验室生成的基因型与 COSMIC（癌症体细胞突变目录）中的基因型合并来创建全面的突变列表；质量控制以及随后从 HGVS 格式的 cDNA 和蛋白质突变中检索基因组坐标；通过转移性黑色素瘤样本的外显子组测序，对一系列与黑色素瘤有关的基因进行通路分析； Itk缺陷小鼠胸腺细胞基因调控区的预测；整理多中心调查数据，研究葡萄糖脑苷脂酶突变与路易体痴呆之间的关联；和分析序列轨迹以检测斑马鱼 TILLING 项目的突变 正在进行的科学项目包括使用 NextGen 序列数据对 Mnemiopsis 基因组进行注释；通过 RNA-seq 检测早期发育过程中基因和亚型表达的变化； Mnemiopsis人类疾病基因直系同源物分析；分析序列痕迹以检测肿瘤样本中假定癌基因的突变；开发人类畸形术语工具，使临床医生能够构建和维护可下载的患者病情电子表格；脊椎动物、无脊椎动物和植物基因组中大外显子的表征；乳腺癌信息核心 (BIC) 的持续更新和改进；开发生物信息学流程，使用 Illumina 序列标签绘制斑马鱼逆转录病毒整合位点，并识别 ENSEMBL 注释基因内发生的整合；开发网站和数据库来搜索集成站点；分析 RNA-seq 数据以研究 Fanconia 贫血患者的选择性剪接；随着时间的推移，分析选定组织类型中的可变剪接基因；鉴定一组 500 个甲基化标记，对不同类型的肿瘤进行分类；通过 ChIP-seq 鉴定 RRP1B 的 DNA 结合位点；确定RRP1B敲低对基因表达的影响；开发定制的 SQL 数据库，用于存储和计算大量犬基因型、表型、序列、变异、样本数据和谱系数据记录；分析 ChIP-seq 数据，以确定狗膀胱肿瘤细胞系中特定组蛋白修饰的基因组位置； RNA-seq 数据的基因组引导、从头开始和从头转录组装；通过 ChIP-seq 分析来研究小鼠增强子位点上的 Sox10 转录因子结合，并将 Sox10 结合与 EP300 和 H3K4Me1 结合相关联；转录因子与实验和预测转录因子结合位点的映射和注释；开发一项基于网络的调查，研究女性对医生与患者谈论体重的技术有何看法（体重管理互动研究）；识别共变突变和对肿瘤亚型进行分类的途径；测量胸腺细胞在四种不同刺激和四种不同突变下的基因表达变化；从 RNAi 筛选中选择目标生物标志物；进行多物种BLAST来估计蛋白质编码基因的跨物种序列相似性；软件管道，用于根据访客与史密森基因组展览互动时的短信回复创建文字云；为 SBRB PI 与史密森基因组展览联合开发的八项调查开发网络界面和数据收集；并研究沉默突变对 TCGA RNA-seq 数据剪接的影响。