MotifMap: integrative genome-wide maps of regulatory motif sites for model species

<p>Abstract</p> <p>Background</p> <p>A central challenge of biology is to map and understand gene regulation on a genome-wide scale. For any given genome, only a small fraction of the regulatory elements embedded in the DNA sequence have been characterized, and there is great interest in developing computational methods to systematically map all these elements and understand their relationships. Such computational efforts, however, are significantly hindered by the overwhelming size of non-coding regions and the statistical variability and complex spatial organizations of regulatory elements and interactions. Genome-wide catalogs of regulatory elements for all model species simply do not yet exist.</p> <p>Results</p> <p>The MotifMap system uses databases of transcription factor binding motifs, refined genome alignments, and a comparative genomic statistical approach to provide comprehensive maps of candidate regulatory elements encoded in the genomes of model species. The system is used to derive new genome-wide maps for yeast, fly, worm, mouse, and human. The human map contains 519,108 sites for 570 matrices with a False Discovery Rate of 0.1 or less. The new maps are assessed in several ways, for instance using high-throughput experimental ChIP-seq data and AUC statistics, providing strong evidence for their accuracy and coverage. The maps can be usefully integrated with many other kinds of omic data and are available at <url>http://motifmap.igb.uci.edu/</url>.</p> <p>Conclusions</p> <p>MotifMap and its integration with other data provide a foundation for analyzing gene regulation on a genome-wide scale, and for automatically generating regulatory pathways and hypotheses. The power of this approach is demonstrated and discussed using the P53 apoptotic pathway and the Gli hedgehog pathways as examples.</p

Retrotransposon profiling of RNA polymerase III initiation sites

Although retroviruses are relatively promiscuous in choice of integration sites, retrotransposons can display marked integration specificity. In yeast and slime mold, some retrotransposons are associated with tRNA genes (tDNAs). In the Saccharomyces cerevisiae genome, the long terminal repeat retrotransposon Ty3 is found at RNA polymerase III (Pol III) transcription start sites of tDNAs. Ty1, 2, and 4 elements also cluster in the upstream regions of these genes. To determine the extent to which other Pol III-transcribed genes serve as genomic targets for Ty3, a set of 10,000 Ty3 genomic retrotranspositions were mapped using high-throughput DNA sequencing. Integrations occurred at all known tDNAs, two tDNA relics (iYGR033c and ZOD1), and six non-tDNA, Pol III-transcribed types of genes (RDN5, SNR6, SNR52, RPR1, RNA170, and SCR1). Previous work in vitro demonstrated that the Pol III transcription factor (TF) IIIB is important for Ty3 targeting. However, seven loci that bind the TFIIIB loader, TFIIIC, were not targeted, underscoring the unexplained absence of TFIIIB at those sites. Ty3 integrations also occurred in two open reading frames not previously associated with Pol III transcription, suggesting the existence of a small number of additional sites in the yeast genome that interact with Pol III transcription complexes

Identifying and ranking potential driver genes of Alzheimer\u27s disease using multiview evidence aggregation.

MOTIVATION: Late onset Alzheimer\u27s disease is currently a disease with no known effective treatment options. To better understand disease, new multi-omic data-sets have recently been generated with the goal of identifying molecular causes of disease. However, most analytic studies using these datasets focus on uni-modal analysis of the data. Here, we propose a data driven approach to integrate multiple data types and analytic outcomes to aggregate evidences to support the hypothesis that a gene is a genetic driver of the disease. The main algorithmic contributions of our article are: (i) a general machine learning framework to learn the key characteristics of a few known driver genes from multiple feature sets and identifying other potential driver genes which have similar feature representations, and (ii) A flexible ranking scheme with the ability to integrate external validation in the form of Genome Wide Association Study summary statistics. While we currently focus on demonstrating the effectiveness of the approach using different analytic outcomes from RNA-Seq studies, this method is easily generalizable to other data modalities and analysis types. RESULTS: We demonstrate the utility of our machine learning algorithm on two benchmark multiview datasets by significantly outperforming the baseline approaches in predicting missing labels. We then use the algorithm to predict and rank potential drivers of Alzheimer\u27s. We show that our ranked genes show a significant enrichment for single nucleotide polymorphisms associated with Alzheimer\u27s and are enriched in pathways that have been previously associated with the disease. AVAILABILITY AND IMPLEMENTATION: Source code and link to all feature sets is available at https://github.com/Sage-Bionetworks/EvidenceAggregatedDriverRanking

Lessons Learned from the First 10 Years of the Oaks and Prairies Joint Venture’s Grassland Restoration Incentive Program (GRIP)

The Oaks and Prairies Joint Venture (OPJV) was formed in 2008 as a public-private partnership of agencies and organizations working across jurisdictional boundaries in portions of Texas and Oklahoma, USA. The OPJV’s major focus is reversing declines of bird populations by supporting strategic habitat conservation (biological planning, conservation design, conservation delivery, mission-based monitoring, and assumption-driven research) for northern bobwhite (Colinus virginianus), grasslandobligate species, and their respective habitats. Our objective for this paper is to document and share a decade of lessons learned in developing a partnership-based native grassland conservation program to meet grassland bird conservation targets. We share lessons learned about how to manage partnership-based, large-scale habitat incentive programs to better target project locations and habitat practice types. To establish initial shared purpose, OPJV partners drew from population and habitat objectives in various state, national, and international bird conservation plans, stepped down to ecoregion levels, to establish the OPJV Grassland Bird Conservation Business Plan. The plan has 4 strategies directly contributing to the achievement of OPJV grassland bird biological objectives that are directly supported by OPJV staff or resources (or both). The overall objective for 2015–2025 was 619,978 ha (1,532,000 acres) improved within 40 focal counties, representing 1/3 of all counties in the OPJV. Our main strategy was to provide financial incentives through the OPJV Grassland Restoration Incentive Program (GRIP) to private landowners for conducting beneficial grassland bird habitat management practices. Since inception in 2013, GRIP has treated over 44,515 ha (110,000 acres) on private lands in Texas and Oklahoma, with the goal of maintaining highquality grassland bird habitat on treated hectares for ≥5 years. In 2017, OPJV partners working with USDA Natural Resources Conservation Service, began a 5-year, $6.1 million partnership to provide additional technical and financial assistance to private landowners interested in grassland conservation through the Regional Conservation Partnership Program (RCPP). A project scoring system was designed to strategically encourage individual projects to include prescribed fire—one of the lowest cost practices per hectare—as a recurring practice to maintain program-achieved grassland improvements. Post-inception of the RCPP, the area treated with prescribed fire increased from approximately 809 ha (2,000 acres)/year to 3,237 ha (8,000 acres)/ year, while maintaining average annual hectares of all other beneficial practices. Beginning in 2013, bird point count surveys were conducted annually to monitor northern bobwhite and grassland bird populations, including a subset of points under the National Bobwhite Conservation Initiative (NBCI) Coordinated Implementation Plan. To date, nearly 25,000 individual point counts have been performed in Texas (n = 20,111) and Oklahoma (n = 4,558). Working together, OPJV partners have made significant progress toward meeting grassland bird habitat and population objectives, while tracking progress and improving methods. However, there is still considerable work ahead

Drilling their own graves:How the European oil and gas supermajors avoid sustainability tensions through mythmaking

This study explores how paradoxical tensions between economic growth and environmental protection are avoided through organizational mythmaking. By examining the European oil and gas supermajors’ ‘‘CEOspeak’’ about climate change, we show how mythmaking facilitates the disregarding, diverting, and/or displacing of sustainability tensions. In doing so, our findings further illustrate how certain defensive responses are employed: (1) regression, or retreating to the comforts of past familiarities, (2) fantasy, or escaping the harsh reality that fossil fuels and climate change are indeed irreconcilable, and (3) projecting, or shifting blame to external actors for failing to address climate change. By highlighting the discursive effects of enacting these responses, we illustrate how the European oil and gas supermajors self-determine their inability to substantively address the complexities of climate change. We thus argue that defensive responses are not merely a form of mismanagement as the paradox and corporate sustainability literature commonly suggests, but a strategic resource that poses serious ethical concerns given the imminent danger of issues such as climate change

Less Than a state, more than an international organization: The Sui generis nature of the European Union

In this paper, I show that the European Union (EU) is less than a state, but more than an international organization. Although it possesses some characteristics of both, the European Union is, I argue, a sui generis project: Although the EU wields extensive influence in some policy areas (such as competition policy or international trade regulation), its institutions’ powers are quite limited in many areas that remain firmly within the grasp of its Member States’ governments (such as security, justice, tax or redistribution policies). The European Union’s supranational elements – especially the EU laws’ supremacy over the laws of individual Member States – distinguish it, furthermore, from international organizations, such as the United Nations or the World Trade Organization. I conclude that the European Union is really a sui generis project that has not been attempted anywhere else: As such, it could be regarded as a useful case study, or perhaps even a “pilot project,” for regional integration projects elsewhere

Plot of counts, should be flagged

<p>Plot of counts that should be flagged based on Cook's distance in F3 (for Wald comparison of F1 vs F3).</p