Ten years of Genome Medicine.

This year marks the 10th anniversary of Genome Medicine. The journal was launched to meet the need in the community for a platform to publish impactful and open science that advances basic and clinical research—using genetic, genomic, omic, and systems approaches—that has the potential to revolutionize the practice of medicine. We have seen the journal evolve along with the changing landscape of health and disease, including the increasing use of genome-scale approaches in medical research and clinical practice, the generation and analysis of patient- and population-level data, and the clinical implementation of these approaches in precision medicine and public health. Genome Medicine, guided by our renowned Section Editors, continues to serve an ever-growing community of interdisciplinary researchers. Here, our Section Editors discuss the major advances in the field and their applications in genomic medicine during the past decade

Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement

Cecile Janssens and colleagues present the GRIPS Statement, a checklist to help strengthen the reporting of genetic risk prediction studies

Declining Sex Ratio in a First Nation Community

Members of the Aamjiwnaang First Nation community near Sarnia, Ontario, Canada, voiced concerns that there appeared to be fewer male children in their community in recent years. In response to these concerns, we assessed the sex ratio (proportion of male births) of the Aamjiwnaang First Nation over the period 1984–2003 as part of a community-based participatory research project. The trend in the proportion of male live births of the Aamjiwnaang First Nation has been declining continuously from the early 1990s to 2003, from an apparently stable sex ratio prior to this time. The proportion of male births (m) showed a statistically significant decline over the most recent 10-year period (1994–2003) (m = 0.412, p = 0.008) with the most pronounced decrease observed during the most recent 5 years (1999–2003) (m = 0.348, p = 0.006). Numerous factors have been associated with a decrease in the proportion of male births in a population, including a number of environmental and occupational chemical exposures. This community is located within the Great Lakes St. Clair River Area of Concern and is situated immediately adjacent to several large petrochemical, polymer, and chemical industrial plants. Although there are several potential factors that could be contributing to the observed decrease in sex ratio of the Aamjiwnaang First Nation, the close proximity of this community to a large aggregation of industries and potential exposures to compounds that may influence sex ratios warrants further assessment into the types of chemical exposures for this population. A community health survey is currently under way to gather more information about the health of the Aamjiwnaang community and to provide additional information about the factors that could be contributing to the observed decrease in the proportion of male births in recent years

Case study of the cascading effects on critical infrastructure in Torbay coastal/pluvial flooding with climate change and 3D visualisation

This is the final version. Available on open access from IWA Publishing via the DOI in this record.Critical infrastructures (CIs) are commonly designed, built and maintained based on rigorous standards in order to withstand the climate and weather-related pressures. However, shifts in climate characteristics may result in increases of the magnitude and frequency of potential risks, or expose specific CI to new or increased risks not previously considered. As vital components of the normal functioning of modern societies, their resilience encompasses the operational elements, their structural integrity and the capacity to maximise business output under climate stressors. In this work, we apply an integrated and participatory methodological approach to assess the risk and enhance the resilience of interconnected CIs to urban flooding under climate change. The proposed methodology has been applied to an extended case study in Torbay to extend previous works (Gibson et al. 2018), which seeks to protect coastal communities from future through using the proposed methodology to justify future investment in coastal defences, as a part of the validation of EU-CIRCLE projects developed methodologies.Natural Environment Research Council (NERC)UK Royal Academy of EngineeringEuropean UnionEngineering and Physical Sciences Research Council (EPSRC

Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers

© 2016 Zhang et al. Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis

Reporting of Human Genome Epidemiology (HuGE) association studies: An empirical assessment

<p>Abstract</p> <p>Background</p> <p>Several thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies.</p> <p>Methods</p> <p>Articles were randomly selected from a continuously updated database of human genome epidemiology association studies to be representative of genetic epidemiology literature. The main analysis evaluated 315 articles published in 2001–2003. For a comparative update, we evaluated 28 more recent articles published in 2006, focusing on issues that were poorly reported in 2001–2003.</p> <p>Results</p> <p>During both time periods, most studies comprised relatively small study populations and examined one or more genetic variants within a single gene. Articles were inconsistent in reporting the data needed to assess selection bias and the methods used to minimize misclassification (of the genotype, outcome, and environmental exposure) or to identify population stratification. Statistical power, the use of unrelated study participants, and the use of replicate samples were reported more often in articles published during 2006 when compared with the earlier sample.</p> <p>Conclusion</p> <p>We conclude that many items needed to assess error and bias in human genome epidemiology association studies are not consistently reported. Although some improvements were seen over time, reporting guidelines and online supplemental material may help enhance the transparency of this literature.</p

The subchalcogenides Ir₂In₈Q (Q = S, Se, Te): Dirac semimetal candidates with re-entrant structural modulation

Subchalcogenides are uncommon compounds where the metal atoms are in unusually low formal oxidation states. They bridge the gap between intermetallics and semiconductors, and can have unexpected structures and properties because of the exotic nature of their chemical bonding, as they contain both metal-metal and metal-main group (e.g. halide, chalcogenide) interactions. Finding new members of this class of materials presents synthetic challenges, as attempts to make them often result in phase separation into binary compounds. We overcome this difficulty by utilizing indium as a metal flux to synthesize large (mm scale) single crystals of novel subchalcogenide materials. Herein, we report two new compounds Ir2In8Q (Q = Se, Te) and compare their structural and electrical properties to the previously reported Ir2In8S analogue. Ir2In8Se and Ir2In8Te crystallize in the P42/mnm space group and are isostructural to Ir2In8S but also have commensurately modulated (with q-vectors q = 1/6a* + 1/6b* and q= 1/10a* + 1/10b* for Ir2In8Se and Ir2In8Te, respectively) low temperature phase transitions, where the chalcogenide anions in the channels experience a distortion in the form of In-Q bond alternation along the ab plane. Both compounds display re-entrant structural behavior, where the supercells appear on cooling but revert to the original subcell below 100 K, suggesting competing structural and electronic interactions dictate the overall structure. Notably, these materials are topological semimetal candidates with symmetry-protected Dirac crossings near the Fermi level, and exhibit high electron mobilities (~1500 cm2 V-1 s-1 at 1.8 K) and moderate carrier concentrations (~1020 cm-3) from charge transport measurements. This work highlights metal flux as a powerful synthetic route to high quality single crystals of novel intermetallic subchalcogenides

An automatic method to generate domain-specific investigator networks using PubMed abstracts

<p>Abstract</p> <p>Background</p> <p>Collaboration among investigators has become critical to scientific research. This includes ad hoc collaboration established through personal contacts as well as formal consortia established by funding agencies. Continued growth in online resources for scientific research and communication has promoted the development of highly networked research communities. Extending these networks globally requires identifying additional investigators in a given domain, profiling their research interests, and collecting current contact information. We present a novel strategy for building investigator networks dynamically and producing detailed investigator profiles using data available in PubMed abstracts.</p> <p>Results</p> <p>We developed a novel strategy to obtain detailed investigator information by automatically parsing the affiliation string in PubMed records. We illustrated the results by using a published literature database in human genome epidemiology (HuGE Pub Lit) as a test case. Our parsing strategy extracted country information from 92.1% of the affiliation strings in a random sample of PubMed records and in 97.0% of HuGE records, with accuracies of 94.0% and 91.0%, respectively. Institution information was parsed from 91.3% of the general PubMed records (accuracy 86.8%) and from 94.2% of HuGE PubMed records (accuracy 87.0). We demonstrated the application of our approach to dynamic creation of investigator networks by creating a prototype information system containing a large database of PubMed abstracts relevant to human genome epidemiology (HuGE Pub Lit), indexed using PubMed medical subject headings converted to Unified Medical Language System concepts. Our method was able to identify 70–90% of the investigators/collaborators in three different human genetics fields; it also successfully identified 9 of 10 genetics investigators within the PREBIC network, an existing preterm birth research network.</p> <p>Conclusion</p> <p>We successfully created a web-based prototype capable of creating domain-specific investigator networks based on an application that accurately generates detailed investigator profiles from PubMed abstracts combined with robust standard vocabularies. This approach could be used for other biomedical fields to efficiently establish domain-specific investigator networks.</p