Faculty Bibliography

BACKGROUND: Due to the recent rapid development in ChIP-seq technologies, which uses high-throughput next-generation DNA sequencing to identify the targets of Chromatin Immunoprecipitation, there is an increasing amount of sequencing data being generated that provides us with greater opportunity to analyze genome-wide protein-DNA interactions. In particular, we are interested in evaluating and enhancing computational and statistical techniques for locating protein binding sites. Many peak detection systems have been developed; in this study, we utilize the following six: CisGenome, MACS, PeakSeq, QuEST, SISSRs, and TRLocator. RESULTS: We define two methods to merge and rescore the regions of two peak detection systems and analyze the performance based on average precision and coverage of transcription start sites. The results indicate that ChIP-seq peak detection can be improved by fusion using score or rank combination. CONCLUSION: Our method of combination and fusion analysis would provide a means for generic assessment of available technologies and systems and assist researchers in choosing an appropriate system (or fusion method) for analyzing ChIP-seq data. This analysis offers an alternate approach for increasing true positive rates, while decreasing false positive rates and hence improving the ChIP-seq peak identification process.

Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl(2) for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3), a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s) underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq) and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq). The effect of NiCl(2) treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs) on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl(2). This study may provide insights into the epigenetic mechanism(s) underlying the carcinogenicity of nickel compounds

We provide a brief description of a Wikibook open-content textbook that was set up with a goal of providing a comprehensive and continually updated list of all of the software packages of interest to the cryo-EM community. While the content of the Wikibook will change over time, here we provide a snapshot of the current state of software tools available, and encourage the members of this community to view the pages, add content, correct errors, and make any other contributions that might be useful

BACKGROUND: Relatively few studies have rigorously assessed the effectiveness of computer-based self-assessment in medical education. AIM: To assess whether an online self-assessment tool can be an effective adjunct to a traditional curriculum for second-year medical students. METHODS: The NYU School of Medicine Online Self-Assessment Tool (SOMOSAT) consists of >450 multiple-choice questions spanning disciplines of internal medicine, administered as separate modules focused on individual organ systems. Questions are coded on multiple dimensions, permitting second-year medical students to receive low-stakes, highly specific feedback regarding their knowledge and performance. Students can also review their answers to guide future study. We employed data collected during SOMOSAT operation to assess its utility and effectiveness. RESULTS: Overall, SOMOSAT accurately predicted student performance on future exams. SOMOSAT participants generally performed better than non-participants on subsequent graded course examinations (p < 0.05). Students using SOMOSAT subsequently experienced greater improvement in areas in which they initially performed poorly, compared with those in which they initially performed well. Students reported that SOMOSAT was most helpful in filling knowledge gaps, and providing opportunities to practice exam-style questions. CONCLUSION: The ability of SOMOSAT to enhance learning and exam performance suggests that web-based self-assessment tools can be effective adjuncts to traditional educational methods

In our role as the editors of a special edition of the Journal of Structural Biology published in 1996 and devoted to the development of software tools, we offer our view of past developments and future prospects in this area. The astonishing progress in computer hardware over the past decade has fueled a significant increase in computational power available for the solution of macromolecular structures. At the same time the relatively slow growth and development of the accompanying software reflects the difficulties of developing large, complex and very specialized analytical methods