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 2014-2015 include the detection of gene and isoform expression changes during early development in Mnemiopsis by RNA-seq, updates to the Homeodomain Resource database, evolutionary profiling of human disease genes using phylogenetic and comparative genomics analyses of model organisms, finding novel gene-to-gene interactions in patients with Diamond-Blackfan anemia using a network reconstruction algorithm, identifying DNA binding sites of RRP1B by ChIP-seq, identifying changes in gene expression that occur in patients with hereditary inclusion body myopathies (HIBM) after treatment with neuraminidase, identifying a set of biomarkers that correlates with degree of inflammation during sepsis, comparing gene expression profiles among cohorts to assess response to gene therapy in patients with familial platelet disorder, comparing gene expression profiles in cells with and without MSH2 mutation after treatment with baicalein, analysis of ChIP-seq to investigate Sox10 transcription factor binding at enhancer sites in mouse, and correlating Sox10 binding with EP300 and H3K4Me1 binding; providing advice on project design and on performing ChIP-seq analyses using the MACS pipeline, pathway analysis of genes mutated in leukemia, and discovery of differentially expressed genes in patients with methylmalonic acidemia (MMA) 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; 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, developing a Web-based, interactive interface to be used by NIH study participants as they go through the informed consent process, developing procedures to track expiration dates and change Oracle passwords for all Web applications in response to new security requirements, characterization of large exons in vertebrate, invertebrate, and plant genomes; ongoing updates and improvements to the Breast Cancer Information Core (BIC), creating a database and Web interface for BRCA1 Circos, a visualization resource for functional data on BRCA1 missense variants, identifying differentially expressed genes in samples from patients with different folate levels, creating database and Web interface to display validated CRISPR targets in zebrafish, analysis of RNA-seq data to investigate alternative splicing in Fanconi anemia patients, analysis of alternatively spliced genes in select tissue types over time, RIP (RNA immunoprecipitation)-seq analysis to identify RNAs interacting with RRP1B, correlation of SNP genotypes between different groups of mouse strains, identifying a set of 500 methylation markers that classifies various tumor types, classifying unknown tumor samples based on the set of 500 methylation biomarkers, finding differentially expressed proteins from mass spectrometry data, determining differentially expressed genes via RNA-seq on patients with ablepharon macrostomia syndrome and performing pathway and network analysis, RNA-seq analysis of 180 samples, cases and controls from the MH-GRID study; finding differentially expressed metabolites between various types of T-helper cells, finding metabolite biomarkers that can distinguish among the T-helper cells, using a network reconstruction algorithm to find novel connections between metabolites, identifying differentially expressed genes in individuals with Turner syndrome (monosomy X) with and without bicuspid aortic valves, continuing maintenance of a customized database and Web interface for storing and computing on dog data including genotypes, phenotypes, sequences, variations, samples, and pedigrees; 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 regimens, RNA-seq analysis comparing human melanocytes treated with AZD to untreated controls, ChIP-seq analysis to assess Blimp1 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, developing a Web interface and data collection for eight surveys developed by SBRB PIs, 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 11th offering of this course in 2014 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 665,000 YouTube views of the lectures from the 2010-2014 series to date. Planning has already begun for a new offering of the course in Spring 2016.
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