Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities

<p>Abstract</p> <p>Background</p> <p>Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element.</p> <p>Results</p> <p>This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called Gene expression and Transcription factor activity based Relevance Network (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to <it>E. coli </it>data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of <it>E. coli </it>during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by using our reconstructed network.</p> <p>Conclusions</p> <p>The GTRNetwork algorithm introduces the hidden layer TFA into classic relevance score-based gene regulatory network reconstruction processes. Integrating the TFA biological information with regulatory network reconstruction algorithms significantly improves both detection of new links and reduces that rate of false positives. The application of GTRNetwork on <it>E. coli </it>gene transcriptome data gives a set of potential regulatory links with promising biological significance for isobutanol stress and other conditions.</p

Network motif comparison rationalizes Sec1/Munc18-SNARE regulation mechanism in exocytosis

BackgroundNetwork motifs, recurring subnetwork patterns, provide significant insight into the biological networks which are believed to govern cellular processes. MethodsWe present a comparative network motif experimental approach, which helps to explain complex biological phenomena and increases the understanding of biological functions at the molecular level by exploring evolutionary design principles of network motifs. ResultsUsing this framework to analyze the SM (Sec1/Munc18)-SNARE (N-ethylmaleimide-sensitive factor activating protein receptor) system in exocytic membrane fusion in yeast and neurons, we find that the SM-SNARE network motifs of yeast and neurons show distinct dynamical behaviors. We identify the closed binding mode of neuronal SM (Munc18-1) and SNARE (syntaxin-1) as the key factor leading to mechanistic divergence of membrane fusion systems in yeast and neurons. We also predict that it underlies the conflicting observations in SM overexpression experiments. Furthermore, hypothesis-driven lipid mixing assays validated the prediction. ConclusionTherefore this study provides a new method to solve the discrepancies and to generalize the functional role of SM proteins

Learning together through international collaboration in teacher education in Malaysia. Report of a project to develop a Bachelor of Education (Honours) in Primary Mathematics

Copyright University of Hertfordshire, School of Education 2011Learning together through international collaboration in teacher education in Malaysia is the report of an enterprising partnership between the University of Hertfordshire, UK, the Ministry of Education Malaysia and two Institutes of Teacher Education in Malaysia. Working collaboratively with colleagues in Malaysia, the University of Hertfordshire School of Education designed, validated, supported and quality assured a Bachelor of Education (Honours) degree programme for initial teacher training for a single cohort of 120 students over four years. All the students graduated in 2010. Learning together through international collaboration in teacher education in Malaysia provides a record of the project itself. It also documents in-depth insights from contributors to the project in two main areas: the collaborative approach to working together and issues relating to learning and teaching, including the Action – Reflection – Modelling (ARM) pedagogical approach, which underpinned the degree programme. Senior managers, teacher educators and lecturers share some of their learning from working together to develop and implement the new degree programme. Student teachers voice some experiences from their school placements. They describe how they used ARM; highlight some of the benefits of the approach and identify some of the challenges associated with introducing a different pedagogy in schools as they were 'learning to teach'. There are glimpses of 'lively and attractive' classes in which 'pupils enjoy and feel comfortable to learn' and 'are eager to answer my questions'. School mentors provide additional insights into the student teachers' learning and teaching practice. The richness of the contributions is reflected in the many quotations included in the report. The successful completion of this project was due to the dedication and expertise of many contributors. The findings documented in this report are relevant for all those engaged in international collaboration and teacher education.Final Published versio

VitisNet: ‘‘Omics’’ Integration through Grapevine Molecular Networks

Background: Genomic data release for the grapevine has increased exponentially in the last five years. The Vitis vinifera genome has been sequenced and Vitis EST, transcriptomic, proteomic, and metabolomic tools and data sets continue to be developed. The next critical challenge is to provide biological meaning to this tremendous amount of data by annotating genes and integrating them within their biological context. We have developed and validated a system of Grapevine Molecular Networks (VitisNet). Methodology/Principal Findings: The sequences from the Vitis vinifera (cv. Pinot Noir PN40024) genome sequencing project and ESTs from the Vitis genus have been paired and the 39,424 resulting unique sequences have been manually annotated. Among these, 13,145 genes have been assigned to 219 networks. The pathway sets include 88 ‘‘Metabolic’’, 15 ‘‘Genetic Information Processing’’, 12 ‘‘Environmental Information Processing’’, 3 ‘‘Cellular Processes’’, 21 ‘‘Transport’’, and 80 ‘‘Transcription Factors’’. The quantitative data is loaded onto molecular networks, allowing the simultaneous visualization of changes in the transcriptome, proteome, and metabolome for a given experiment. Conclusions/Significance: VitisNet uses manually annotated networks in SBML or XML format, enabling the integration of large datasets, streamlining biological functional processing, and improving the understanding of dynamic processes in systems biology experiments. VitisNet is grounded in the Vitis vinifera genome (currently at 8x coverage) and can be readily updated with subsequent updates of the genome or biochemical discoveries. The molecular network files can be dynamically searched by pathway name or individual genes, proteins, or metabolites through the MetNet Pathway database and web-portal at http://metnet3.vrac.iastate.edu/. All VitisNet files including the manual annotation of the grape genome encompassing pathway names, individual genes, their genome identifier, and chromosome location can be accessed and downloaded from the VitisNet tab at http://vitis-dormancy.sdstate.org

VitisNet: ‘‘Omics’’ Integration through Grapevine Molecular Networks

Background: Genomic data release for the grapevine has increased exponentially in the last five years. The Vitis vinifera genome has been sequenced and Vitis EST, transcriptomic, proteomic, and metabolomic tools and data sets continue to be developed. The next critical challenge is to provide biological meaning to this tremendous amount of data by annotating genes and integrating them within their biological context. We have developed and validated a system of Grapevine Molecular Networks (VitisNet). Methodology/Principal Findings: The sequences from the Vitis vinifera (cv. Pinot Noir PN40024) genome sequencing project and ESTs from the Vitis genus have been paired and the 39,424 resulting unique sequences have been manually annotated. Among these, 13,145 genes have been assigned to 219 networks. The pathway sets include 88 ‘‘Metabolic’’, 15 ‘‘Genetic Information Processing’’, 12 ‘‘Environmental Information Processing’’, 3 ‘‘Cellular Processes’’, 21 ‘‘Transport’’, and 80 ‘‘Transcription Factors’’. The quantitative data is loaded onto molecular networks, allowing the simultaneous visualization of changes in the transcriptome, proteome, and metabolome for a given experiment. Conclusions/Significance: VitisNet uses manually annotated networks in SBML or XML format, enabling the integration of large datasets, streamlining biological functional processing, and improving the understanding of dynamic processes in systems biology experiments. VitisNet is grounded in the Vitis vinifera genome (currently at 8x coverage) and can be readily updated with subsequent updates of the genome or biochemical discoveries. The molecular network files can be dynamically searched by pathway name or individual genes, proteins, or metabolites through the MetNet Pathway database and web-portal at http://metnet3.vrac.iastate.edu

The Hordeum Toolbox: The Barley Coordinated Agricultural Project Genotype and Phenotype Resource

The use of DNA markers in public sector plant breeding is now the norm. Such markers are common across breeding programs and this commonality enables and enhances collaboration. Therefore, large collaborative research projects that measure several phenotypes across multiple environments coupled with the expanding amount of genotype data attainable with current marker technologies are on the rise and these projects demand efficient data delivery. However, development of computational tools for advanced data integration, visualization, and analysis is still a bottleneck, even though these resources have the greatest potential impact for users who are extracting and developing hypothesis-based solutions. The Hordeum Toolbox (THT) was developed as a data resource for the Barley Coordinated Agricultural Project (CAP) with the novel capability of constructing user-defined downloadable sets of phenotype and/or genotype data for downstream analysis. Internal tools in THT enable users to create clusters of a selected group of lines based on genotype data, parse pedigrees, and select germplasm based on haplotype, phenotype, and agronomic properties. The Hordeum Toolbox can be adapted to breeding programs or collaborations to assist researchers in germplasm selection, genotype data visualization, and the integration of complex data sets for statistical analysisThis is the publisher’s final pdf. The published article is copyrighted by the Crop Science Society of America and can be found at: https://www.crops.org/publications/tp

An Observationally Constrained Evaluation of the Oxidative Capacity in the Tropical Western Pacific Troposphere

Hydroxyl radical (OH) is the main daytime oxidant in the troposphere and determines the atmospheric lifetimes of many compounds. We use aircraft measurements of O3, H2O, NO, and other species from the Convective Transport of Active Species in the Tropics (CONTRAST) field campaign, which occurred in the tropical western Pacific (TWP) during January–February 2014, to constrain a photochemical box model and estimate concentrations of OH throughout the troposphere. We find that tropospheric column OH (OHCOL) inferred from CONTRAST observations is 12 to 40% higher than found in chemical transport models (CTMs), including CAM-chem-SD run with 2014 meteorology as well as eight models that participated in POLMIP (2008 meteorology). Part of this discrepancy is due to a clear-sky sampling bias that affects CONTRAST observations; accounting for this bias and also for a small difference in chemical mechanism results in our empirically based value of OHCOL being 0 to 20% larger than found within global models. While these global models simulate observed O3 reasonably well, they underestimate NOx (NO + NO2) by a factor of two, resulting in OHCOL ~30% lower than box model simulations constrained by observed NO. Underestimations by CTMs of observed CH3CHO throughout the troposphere and of HCHO in the upper troposphere further contribute to differences between our constrained estimates of OH and those calculated by CTMs. Finally, our calculations do not support the prior suggestion of the existence of a tropospheric OH minimum in the TWP, because during January–February 2014 observed levels of O3 and NO were considerably larger than previously reported values in the TWP

Information content and reward processing in the human striatum during performance of a declarative memory task

Negative feedback can signal poor performance, but it also provides information that can help learners reach the goal of task mastery. The primary aim of this study was to test the hypothesis that the amount of information provided by negative feedback during a paired-associate learning task influences feedback-related processing in the caudate nucleus. To do this, we manipulated the number of response options: With two options, positive and negative feedback provide equal amounts of information, whereas with four options, positive feedback provides more information than does negative feedback. We found that positive and negative feedback activated the caudate similarly when there were two response options. With four options, the caudate’s response to negative feedback was reduced. A secondary goal was to investigate the link between brain-based measures of feedback-related processing and behavioral indices of learning. Analysis of the posttest measures showed that trials with positive feedback were associated with higher posttest confidence ratings. Additionally, when positive feedback was delivered, caudate activity was greater for trials with high than with low posttest confidence. This experiment demonstrated the context sensitivity of feedback processing and provided evidence that feedback processing in the striatum can contribute to the strengthening of the representations available within declarative memory

Neuropathologic Correlates of Hippocampal Atrophy in the Elderly: A Clinical, Pathologic, Postmortem MRI Study

The volume of the hippocampus measured with structural magnetic resonance imaging (MRI) is increasingly used as a biomarker for Alzheimer's disease (AD). However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6×10−7) or mild cognitive impairment (P = 9.6×10−7). Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018) and hippocampal sclerosis (P = 4.2×10−7). Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal volume in old age, though the impacts of each pathology on the shape of the hippocampus may differ