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.
