NHGRI/DIR Bioinformatics and Scientific Programming Core

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/NHGRI研究人员正在进行的研究。核心促进获得专业的软件和硬件，开发通用的软件解决方案，可以解决基因组研究中的各种问题，开发数据库解决方案，用于有效存档和检索实验和临床数据，向基因组社区传播新的软件和数据库解决方案。并为NHGRI研究人员和受训人员提供生物信息学方面的教育机会。生物信息学和科学编程核心与生物信息学研究人员之间的大部分合作都集中在旨在推进特定研究项目的协作互动上。为这些项目提供的支助不仅包括数据分析，而且还包括通过国家人类住区研究所/人口与发展研究所的公共网站（http：//www.example.com）收集和传播数据的相关努力。research.nhgri.nih.gov 在本报告所述期间开展的科学项目包括：为外显子组测序试点研究提供生物信息学支持，以确定与极端早发性心脏性猝死有关的遗传变异;通过使用单细胞RNA测序技术调查糖尿病风险的功能基础，目的是在单细胞水平上查询转录组; ChIP-seq分析以确定HIST 1H 1A失调如何影响转录因子和染色质相关蛋白结合; ATAC-seq分析以确定HIST 1A失调如何影响前列腺癌特异性染色质结构; RNA-seq分析比较来自敲除小鼠的野生型与HIST 1H 1A前列腺组织样品中基因的差异表达，以确定HIST 1H 1A如何影响前列腺癌的转移易感性; DHX 15的分子建模和比较二级结构分析，DHX 15是一种参与前mRNA剪接和核糖体生物发生的RNA解旋酶，DHX 15点突变的结果为进一步研究提供了适当的敲除和敲入动物模型的开发信息;开发和实施基因预测管道，用于生物体全基因组测序数据的注释和分析;通过对死后脑组织进行RNAseq分析来分析ADHD中的神经基因表达，以表征具有ADHD病史的青年和匹配的非精神病对照中的神经元基因表达，目的是建立神经元转录组并确定哪些基因和神经基因网络影响ADHD的发展;和生物信息学支持基因组确定队列（GTAC），一个共享的基因组确定队列，至少有10，000个个体的基因组或外显子组已被测序，并可重新进行二次表型研究。 在教育方面，Drs. Zerevanis和沃尔夫斯贝格继续担任基因组分析系列讲座当前主题的共同主任。该课程在2016年的第12次提供包括连续星期三的14个1.5小时的会议，由本地和外部演讲者组成，涵盖基因组学的主要领域。（除了担任课程主任外，Drs. Zevanis和沃尔夫斯贝格还亲自讲授了系列课程中的三堂课。）鉴于参加这些讲座的听众多种多样，讲座面向一年级研究生，强调实践而不是理论方法。每堂课都有讲义和参考书目，每堂课结束时都有充足的时间供提问和讨论。多年来，Drs. Drs. Zevanis和沃尔夫斯贝格确保系列讲座跟上基因组技术和方法的变化，正如课程大纲如何随着每次课程的发展而演变所证明的那样，纳入了随着时间的推移而出现的重要的基因组学和生物信息学的新方面。这门课受欢迎程度的最佳衡量标准是数字。通过使用社交媒体技术，如YouTube和通过各种Facebook和Twitter的饲料覆盖面，该课程的覆盖面已经远远超出了贝塞斯达校园，从2010年到2016年系列讲座的YouTube浏览量超过900，000。计划已经开始在2018年春季提供新的课程。

The NHGRI Bioinformatics and Scientific Programming Core actively supports the research being performed by NHGRI/DIR 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. The majority of engagements between the Bioinformatics and Scientific Programming Core and DIR investigators are focused on collaborative interactions intended to advance specific research projects. The support provided for these projects includes not only data analysis, but related efforts focused on data collection and dissemination through the public NHGRI/DIR Web site (http://research.nhgri.nih.gov) as well. Scientific projects undertaken during the reporting period include providing bioinformatic support for an exome sequencing pilot study to determine genetic variants linked to extreme early-onset sudden cardiac death; investigations of the functional basis of diabetes disease risk through the use of single-cell RNA sequencing technology, with the goal of interrogating the transcriptome at the single-cell level; ChIP-seq analyses to determine how HIST1H1A dysregulation affects transcription factor and chromatin-associated protein binding; ATAC-seq analyses to determine how HISTH1A dysregulation impacts prostate cancer-specific chromatin structure; RNA-seq analyses comparing differential expression of genes in wild type vs. HIST1H1A prostate tissue samples from knock-out mice, to determine how HIST1H1A affects metastasis susceptibility in prostate cancer; molecular modeling and comparative secondary structural analyses of DHX15, an RNA helicase involved in pre-mRNA splicing and ribosome biogenesis, with results from DHX15 point mutations informing the development of appropriate knock-out and knock-in animal models for further study; development and implementation of a gene prediction pipeline for the annotation and analysis of organismal whole-genome sequencing data; profiling neural gene expression in ADHD by performing RNAseq analyses of post-mortem brain tissue to characterize neuronal gene expression in youth with a history of ADHD and matched non-psychiatric controls, with the goal establishing a neuronal transcriptome and determining which genes and neural gene networks influence the development of ADHD; and bioinformatic support for The Genomic Ascertainment Cohort (GTAC), a shared genomic ascertainment cohort of at least 10,000 individuals whose genomes or exomes have been sequenced and are recallable for secondary phenotyping studies. On the educational front, Drs. Baxevanis and Wolfsberg continue to serve as co-directors of the Current Topics in Genome Analysis lecture series. The 12th offering of this course in 2016 consisted of 14 1.5-hour sessions on successive Wednesdays, with a mixture of local and outside speakers covering the major areas of genomics. (Besides serving as the Course Directors, Drs. Baxevanis and Wolfsberg also give three of the lectures in the series themselves.) Given the diverse audience attending these lectures, the lectures have been geared towards first-year graduate students, with an emphasis on practical rather than theoretical approaches. Handouts and reference lists are provided for each lecture, and ample time is allotted at the end of each lecture for questions and discussion. Over the years, Drs. Baxevanis and Wolfsberg have made sure that the lecture series keeps pace with changes in genomic technologies and approaches, as evidenced by how the syllabus for the course has evolved with each offering, incorporating new aspects of genomics and bioinformatics that have emerged as important over time. The best measure of the popularity of this course is in the numbers. Through the use of social media technologies such as YouTube and coverage through various Facebook and Twitter feeds, the reach of the course has gone well-beyond the Bethesda campus, with over 900,000 YouTube views of the lectures from the 2010-2016 series to date. Planning has already begun for a new offering of the course in Spring 2018.