Combining classifiers to predict gene function in Arabidopsis thaliana using large-scale gene expression measurements

<p>Abstract</p> <p>Background</p> <p><it>Arabidopsis thaliana </it>is the model species of current plant genomic research with a genome size of 125 Mb and approximately 28,000 genes. The function of half of these genes is currently unknown. The purpose of this study is to infer gene function in Arabidopsis using machine-learning algorithms applied to large-scale gene expression data sets, with the goal of identifying genes that are potentially involved in plant response to abiotic stress.</p> <p>Results</p> <p>Using in house and publicly available data, we assembled a large set of gene expression measurements for <it>A. thaliana</it>. Using those genes of known function, we first evaluated and compared the ability of basic machine-learning algorithms to predict which genes respond to stress. Predictive accuracy was measured using ROC₅₀and precision curves derived through cross validation. To improve accuracy, we developed a method for combining these classifiers using a weighted-voting scheme. The combined classifier was then trained on genes of known function and applied to genes of unknown function, identifying genes that potentially respond to stress. Visual evidence corroborating the predictions was obtained using electronic Northern analysis. Three of the predicted genes were chosen for biological validation. Gene knockout experiments confirmed that all three are involved in a variety of stress responses. The biological analysis of one of these genes (At1g16850) is presented here, where it is shown to be necessary for the normal response to temperature and NaCl.</p> <p>Conclusion</p> <p>Supervised learning methods applied to large-scale gene expression measurements can be used to predict gene function. However, the ability of basic learning methods to predict stress response varies widely and depends heavily on how much dimensionality reduction is used. Our method of combining classifiers can improve the accuracy of such predictions – in this case, predictions of genes involved in stress response in plants – and it effectively chooses the appropriate amount of dimensionality reduction automatically. The method provides a useful means of identifying genes in <it>A. thaliana </it>that potentially respond to stress, and we expect it would be useful in other organisms and for other gene functions.</p

Plasma microRNA levels following resection of metastatic melanoma

Melanoma remains the leading cause of skin cancer–related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples. Principal component analysis detected underlying patterns of miR expression between pre- vs postsurgical patients. Group A contained 3 of 4 patients with stage IV disease (pre- and postsurgical samples) and 2 patients with stage III disease (postsurgical samples only). The corresponding preoperative samples to both individuals with stage III disease were contained in group B along with 1 individual with stage IV disease (pre- and postsurgical samples). Group A was distinguished from group B by statistically significant analysis of variance changes in miR expression ( P < .0001). This analysis revealed that group A vs group B had downregulation of let-7b-5p, miR-520f, miR-720, miR-4454, miR-21-5p, miR-22-3p, miR-151a-3p, miR-378e, and miR-1283 and upregulation of miR-126-3p, miR-223-3p, miR-451a, let-7a-5p, let-7g-5p, miR-15b-5p, miR-16-5p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-26a-5p, miR-106a-5p, miR-17-5p, miR-130a-3p, miR-142-3p, miR-150-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, and miR-1976. Changes in miR expression were not readily evident in individuals with distant metastatic disease (stage IV) as these individuals may have prolonged inflammatory responses. Thus, inflammatory-driven miRs coinciding with tumor-derived miRs can blunt anticipated changes in expression profiles following surgical resection

Mechanical Harvesting Effectively Controls Young Typha spp. Invasion and Unmanned Aerial Vehicle Data Enhances Post-treatment Monitoring

The ecological impacts of invasive plants increase dramatically with time since invasion. Targeting young populations for treatment is therefore an economically and ecologically effective management approach, especially when linked to post-treatment monitoring to evaluate the efficacy of management. However, collecting detailed field-based post-treatment data is prohibitively expensive, typically resulting in inadequate documentation of the ecological effects of invasive plant management. Alternative approaches, such as remote detection with unmanned aerial vehicles (UAV), provide an opportunity to advance the science and practice of restoration ecology. In this study, we sought to determine the plant community response to different mechanical removal treatments to a dominant invasive wetland macrophyte (Typha spp.) along an age-gradient within a Great Lakes coastal wetland. We assessed the post-treatment responses with both intensive field vegetation and UAV data. Prior to treatment, the oldest Typha stands had the lowest plant diversity, lowest native sedge (Carex spp.) cover, and the greatest Typha cover. Following treatment, plots that were mechanically harvested below the surface of the water differed from unharvested control and above-water harvested plots for several plant community measures, including lower Typha dominance, lower native plant cover, and greater floating and submerged aquatic species cover. Repeated-measures analysis revealed that above-water cutting increased plant diversity and aquatic species cover across all ages, and maintained native Carex spp. cover in the youngest portions of Typha stands. UAV data revealed significant post-treatment differences in normalized difference vegetation index (NDVI) scores, blue band reflectance, and vegetation height, and these remotely collected measures corresponded to field observations. Our findings suggest that both mechanically harvesting the above-water biomass of young Typha stands and harvesting older stands below-water will promote overall native community resilience, and increase the abundance of the floating and submerged aquatic plant guilds , which are the most vulnerable to invasions by large macrophytes. UAV’s provided fast and spatially expansive data compared to field monitoring, and effectively measured plant community structural responses to different treatments. Study results suggest pairing UAV flights with targeted field data collection to maximize the quality of post-restoration vegetation monitoring

Rules of engagement promote polarity in RNA trafficking

Many cell biological pathways exhibit overall polarity (net movement of molecules in one direction) even though individual molecular interactions in the pathway are freely reversible. The A2 RNA trafficking pathway exhibits polarity in moving specific RNA molecules from the nucleus to localization sites in the myelin compartment of oligodendrocytes or dendritic spines in neurons. The A2 pathway is mediated by a ubiquitously expressed trans-acting trafficking factor (hnRNP A2) that interacts with a specific 11 nucleotide cis-acting trafficking sequence termed the A2 response element (A2RE) found in several localized RNAs. Five different molecular partners for hnRNP A2 have been identified in the A2 pathway: hnRNP A2 itself, transportin, A2RE RNA, TOG (tumor overexpressed gene) and hnRNP E1, each playing a key role in one particular step of the A2 pathway. Sequential interactions of hnRNP A2 with different molecular partners at each step mediate directed movement of trafficking intermediates along the pathway. Specific "rules of engagement" (both and, either or, only if) govern sequential interactions of hnRNP A2 with each of its molecular partners. Rules of engagement are defined experimentally using three component binding assays to measure differential binding of hnRNP A2 to one partner in the presence of each of the other partners in the pathway. Here we describe rules of engagement for hnRNP A2 binding to each of its molecular partners and discuss how these rules of engagement promote polarity in the A2 RNA trafficking pathway. For molecules with multiple binding partners, specific rules of engagement govern different molecular interactions. Rules of engagement are ultimately determined by structural relationships between binding sites on individual molecules. In the A2 RNA trafficking pathway rules of engagement governing interactions of hnRNP A2 with different binding partners provide the basis for polarity of movement of intermediates along the pathway

Uptake and effectiveness of the Children's Fitness Tax Credit in Canada: the rich get richer

<p>Abstract</p> <p>Background</p> <p>The Government of Canada implemented a Children's Fitness Tax Credit (CFTC) in 2007 which allows a non-refundable tax credit of up to $500 to register a child in an eligible physical activity (PA) program. The purposes of this study were to assess whether the awareness, uptake, and perceived effectiveness of this tax credit varied by household income among Canadian parents.</p> <p>Methods</p> <p>An internet-based panel survey was conducted in March 2009 with a representative sample of 2135 Canadians. Of those, parents with children aged 2 to 18 years of age (<it>n </it>= 1004) were asked if their child was involved in organized PA programs (including dance and sports), the associated costs to register their child in these programs, awareness of the CFTC, if they had claimed the CFTC for the tax year 2007, and whether they planned to claim it in the upcoming year. Parents were also asked if they believed the CFTC has lead to their child being more involved in PA programs.</p> <p>Results</p> <p>Among parents, 54.4% stated their child was in organized PA and 55.5% were aware of the CFTC. Parents in the lowest income quartile were significantly less aware and less likely to claim the CFTC than other income groups. Among parents who had claimed the CFTC, few (15.6%) believed it had increased their child's participation in PA programs.</p> <p>Conclusions</p> <p>More than half of Canadian parents with children have claimed the CFTC. However, the tax credit appears to benefit the wealthier families in Canada.</p

New DArT markers for oat provide enhanced map coverage and global germplasm characterization

BACKGROUND: Genomic discovery in oat and its application to oat improvement have been hindered by a lack of genetic markers common to different genetic maps, and by the difficulty of conducting whole-genome analysis using high-throughput markers. This study was intended to develop, characterize, and apply a large set of oat genetic markers based on Diversity Array Technology (DArT). RESULTS: Approximately 19,000 genomic clones were isolated from complexity-reduced genomic representations of pooled DNA samples from 60 oat varieties of global origin. These were screened on three discovery arrays, with more than 2000 polymorphic markers being identified for use in this study, and approximately 2700 potentially polymorphic markers being identified for use in future studies. DNA sequence was obtained for 2573 clones and assembled into a non-redundant set of 1770 contigs and singletons. Of these, 705 showed highly significant (Expectation < 10E-10) BLAST similarity to gene sequences in public databases. Based on marker scores in 80 recombinant inbred lines, 1010 new DArT markers were used to saturate and improve the 'Kanota' × 'Ogle' genetic map. DArT markers provided map coverage approximately equivalent to existing markers. After binning markers from similar clones, as well as those with 99% scoring similarity, a set of 1295 non-redundant markers was used to analyze genetic diversity in 182 accessions of cultivated oat of worldwide origin. Results of this analysis confirmed that major clusters of oat diversity are related to spring vs. winter type, and to the presence of major breeding programs within geographical regions. Secondary clusters revealed groups that were often related to known pedigree structure. CONCLUSION: These markers will provide a solid basis for future efforts in genomic discovery, comparative mapping, and the generation of an oat consensus map. They will also provide new opportunities for directed breeding of superior oat varieties, and guidance in the maintenance of oat genetic diversity

Using Ethnographic Methods to Articulate Community-Based Conceptions of Cultural Heritage Management

How can ethnographic methods help communities articulate and enact their own conceptions of heritage management? This and related questions are being explored through an international research project, ‘Intellectual Property Issues in Cultural Heritage’. The project includes up to twenty community- based initiatives that incorporate community-based participatory research and ethnographic methods to explore emerging intellectual property-related issues in archaeological contexts; the means by which they are being addressed or resolved; and the broader implications of these issues and concerns. We discuss three examples that use ethnography to (a) articulate local or customary laws and principles of archaeological heritage management among a First Nations group in British Columbia; (b) assemble knowledge related to land/sea use and cultural practices of the Moriori people of Rekohu (Chatham Islands) for their use in future land and heritage manage- ment policies; and (c) aid a tribal cultural centre in Michigan in crafting co-management strategies to protect spiritual traditions associated with a rock art site on state property. Such situations call for participatory methods that place control over the design, process, products, and interpretation of ‘archaeology’ in the hands of cultural descendants. We hope that these examples of community-based conceptions of archaeological heritage management, facilitated through ethnographic methods and participatory approaches, will increase awareness of the value of these and other alternative approaches and the need to share them widely

An intergenerational study of perceptions of changes in active free play among families from rural areas of Western Canada

Background: Children's engagement in active free play has declined across recent generations. Therefore, the purpose of this study was to examine perceptions of intergenerational changes in active free play among families from rural areas. We addressed two research questions: (1) How has active free play changed across three generations? (2) What suggestions do participants have for reviving active free play? Methods: Data were collected via 49 individual interviews with members of 16 families (15 grandparents, 16 parents, and 18 children) residing in rural areas/small towns in the Province of Alberta (Canada). Interview recordings were transcribed verbatim and subjected to thematic analysis guided by an ecological framework of active free play. Results: Factors that depicted the changing nature of active free play were coded in the themes of less imagination/more technology, safety concerns, surveillance, other children to play with, purposeful physical activity, play spaces/organized activities, and the good parenting ideal. Suggestions for reviving active free play were coded in the themes of enhance facilities to keep kids entertained, provide more opportunities for supervised play, create more community events, and decrease use of technology. Conclusions: These results reinforce the need to consider multiple levels of social ecology in the study of active free play, and highlight the importance of community-based initiatives to revive active free play in ways that are consistent with contemporary notions of good parentin