Enzymes Are Enriched in Bacterial Essential Genes

Essential genes, those indispensable for the survival of an organism, play a key role in the emerging field, synthetic biology. Characterization of functions encoded by essential genes not only has important practical implications, such as in identifying antibiotic drug targets, but can also enhance our understanding of basic biology, such as functions needed to support cellular life. Enzymes are critical for almost all cellular activities. However, essential genes have not been systematically examined from the aspect of enzymes and the chemical reactions that they catalyze. Here, by comprehensively analyzing essential genes in 14 bacterial genomes in which large-scale gene essentiality screens have been performed, we found that enzymes are enriched in essential genes. Essential enzymes have overrepresented ligases (especially those forming carbon-oxygen bonds and carbon-nitrogen bonds), nucleotidyltransferases and phosphotransferases, while have underrepresented oxidoreductases. Furthermore, essential enzymes tend to associate with more gene ontology domains. These results, from the aspect of chemical reactions, provide further insights into the understanding of functions needed to support natural cellular life, as well as synthetic cells, and provide additional parameters that can be integrated into gene essentiality prediction algorithms

Genome-wide essential gene identification in Streptococcus sanguinis

A clear perception of gene essentiality in bacterial pathogens is pivotal for identifying drug targets to combat emergence of new pathogens and antibiotic-resistant bacteria, for synthetic biology, and for understanding the origins of life. We have constructed a comprehensive set of deletion mutants and systematically identified a clearly defined set of essential genes for Streptococcus sanguinis. Our results were confirmed by growing S. sanguinis in minimal medium and by double-knockout of paralogous or isozyme genes. Careful examination revealed that these essential genes were associated with only three basic categories of biological functions: maintenance of the cell envelope, energy production, and processing of genetic information. Our finding was subsequently validated in two other pathogenic streptococcal species, Streptococcus pneumoniae and Streptococcus mutans and in two other gram-positive pathogens, Bacillus subtilis and Staphylococcus aureus. Our analysis has thus led to a simplified model that permits reliable prediction of gene essentiality

Studying neuroanatomy using MRI

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging, and disease. Developments in MRI acquisition, image processing, and data modelling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and inferring microstructural properties; we also describe key artefacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, though methods need to improve and caution is required in its interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

eRegistries: Electronic registries for maternal and child health.

The Global Roadmap for Health Measurement and Accountability sees integrated systems for health information as key to obtaining seamless, sustainable, and secure information exchanges at all levels of health systems. The Global Strategy for Women's, Children's and Adolescent's Health aims to achieve a continuum of quality of care with effective coverage of interventions. The WHO and World Bank recommend that countries focus on intervention coverage to monitor programs and progress for universal health coverage. Electronic health registries - eRegistries - represent integrated systems that secure a triple return on investments: First, effective single data collection for health workers to seamlessly follow individuals along the continuum of care and across disconnected cadres of care providers. Second, real-time public health surveillance and monitoring of intervention coverage, and third, feedback of information to individuals, care providers and the public for transparent accountability. This series on eRegistries presents frameworks and tools to facilitate the development and secure operation of eRegistries for maternal and child health.In this first paper of the eRegistries Series we have used WHO frameworks and taxonomy to map how eRegistries can support commonly used electronic and mobile applications to alleviate health systems constraints in maternal and child health. A web-based survey of public health officials in 64 low- and middle-income countries, and a systematic search of literature from 2005-2015, aimed to assess country capacities by the current status, quality and use of data in reproductive health registries.eRegistries can offer support for the 12 most commonly used electronic and mobile applications for health. Countries are implementing health registries in various forms, the majority in transition from paper-based data collection to electronic systems, but very few have eRegistries that can act as an integrating backbone for health information. More mature country capacity reflected by published health registry based research is emerging in settings reaching regional or national scale, increasingly with electronic solutions. 66 scientific publications were identified based on 32 registry systems in 23 countries over a period of 10 years; this reflects a challenging experience and capacity gap for delivering sustainable high quality registries.Registries are being developed and used in many high burden countries, but their potential benefits are far from realized as few countries have fully transitioned from paper-based health information to integrated electronic backbone systems. Free tools and frameworks exist to facilitate progress in health information for women and children