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. Scientific projects completed in 2015-2016 include creating a database and Web interface for BRCA1 Circos, a visualization resource for functional data on BRCA1 missense variants; reating database and Web interface to display validated CRISPR targets in zebrafish, analysis of alternatively spliced genes in select tissue types over time, RNA immunoprecipitation)-seq analysis to identify RNAs interacting with RRP1B, and RNA-seq analysis of 180 samples, cases and controls from the MH-GRID study. Ongoing scientific projects include the annotation and analysis of two newly sequenced Hydractinia genomes, including comparison of whole genome alignment strategies and evaluation of visualization tools; development of computational methods to analyze RNA-seq data obtained from the zebrafish translatome, assessing mRNA that is being actively translated; analysis of sequence traces to detect mutations in putative oncogenes in tumor samples, developing a Web interface to return ClinSeq variant results to patients, implementing the ExAC variant browser at NHGRI and populating it with ClinSeq exome data, developing a Web interface for a hierarchical taxonomy of clinical genomic uncertainty, creation of an online tool to facilitate a systematic review of sickle cell trait publications, characterization of large exons in vertebrate, invertebrate, and plant genomes; ongoing updates and improvements to the Breast Cancer Information Core (BIC), identifying differentially expressed genes in samples from patients with different folate levels, analysis of RNA-seq data to investigate alternative splicing in Fanconi anemia patients, correlation of SNP genotypes between different groups of mouse strains, analysis of RNA-seq data and eQTL mapping with Diversity Outbred mice to identify germline variation that influenes aggressive forms of prostate cancer, determining differentially expressed genes via RNA-seq on patients with ablepharon macrostomia syndrome and performing pathway and network analysis, refining a list of genes that are differentially expressed between wildtype and kctd7 knockouts in zebrafish, identifying the genes that are differentially expressed between wildtype and pus3 knockouts in zebrafish, ChIP-seq analysis to assess EBF3 binding in cells overexpressing wild type and mutant forms of the transcription factor, assessing the gene expression profile of bone marrow cells in which genes associated with leukemia have been mutagenized; developing a method to identify metabolic biomarkers that can distinguish among five different types of T helper cells, identifying differentially expressed genes in individuals with Turner syndrome (monosomy X) with and without bicuspid aortic valves, creating a database and Web interface for the Atlas of Human Malformation Syndromes in Diverse Populations, an online tool to help clinicians diagnose syndromic disorders across diverse populations; continuing maintenance of a customized database and Web interface for storing and computing on dog data including genotypes, phenotypes, sequences, variations, samples, and pedigrees; re-development of the Dog Genome Project Web site, including the integration of several new participant forms, research protocols and canine linkage maps, program information, and study data; RNA-seq analysis in melanA and CoCl2-treated mouse cells, RNA-seq analysis in mouse melanocyte stem cells, identifying gene expression changes in cells from NPC patients treated with different drug regimen, RNA-seq analysis comparing human melanocytes treated with AZD to untreated controls, statistical analysis for a behavioral study of neuromuscular control in mice on different drug therapies, selection of biomarkers that can differentiate between different stages of melanoma, network and pathway analysis of genes that influence body composition in zebrafish, ChIP-seq analysis to assess Bimp1 and Tcf1 transcription factor binding in TFH and TH1 cells, measuring gene expression changes in thymocytes over four different stimulations and four different mutations, biomarker selection of targets from RNAi screens, identifying differentially expressed genes after GBA knockdown in Gaucher disease, network reconstruction to find novel connections between genes involved in Gaucher disease and those involved in Parkinsons disease, clustering of clinical biomarkers across patients with Gaucher disease, as well as Gaucher disease with Parkinsons disease; development of a Web interface and data collection for eight surveys developed by Social and Behavioral Research Branch investigators, developing a new method, based on eQTL analysis, to analyze gene expression changes caused by DNA integration; and identifying changes in gene expression in male and female patients with methylmalonic acidemia and homocysteinemia, cblX type. 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 775,000 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.
