Towards automatic classification within the ChEBI ontology

*Background*
Appearing in a wide variety of contexts, biochemical 'small molecules' are a core element of biomedical data. Chemical ontologies, which provide stable identifiers and a shared vocabulary for use in referring to such biochemical small molecules, are crucial to enable the interoperation of such data. One such chemical ontology is ChEBI (Chemical Entities of Biological Interest), a candidate member ontology of the OBO Foundry. ChEBI is a publicly available, manually annotated database of chemical entities and contains around 18000 annotated entities as of the last release (May 2009). ChEBI provides stable unique identifiers for chemical entities; a controlled vocabulary in the form of recommended names (which are unique and unambiguous), common synonyms, and systematic chemical names; cross-references to other databases; and a structural and role-based classification within the ontology. ChEBI is widely used for annotation of chemicals within biological databases, text-mining, and data integration. ChEBI can be accessed online at "http://www.ebi.ac.uk/chebi/":http://www.ebi.ac.uk/chebi/ and the full dataset is available for download in various formats including SDF and OBO.

*Automated Classification*
The selection of chemical entities for inclusion in the ChEBI database is user-driven. As the use of ChEBI has grown, so too has the backlog of user-requested entries. Inevitably, the annotation backlog creates a bottleneck, and to speed up the annotation process, ChEBI has recently released a submission tool which allows community submissions of chemical entities, groups, and classes. However, classification of chemical entities within the ontology is a difficult and niche activity, and it is unlikely that the community as a whole will be able or willing to correctly and consistently classify each submitted entity, creating required classes where they are missing. As a result, it is likely that while the size of the database grows, the ontological classification will become less sophisticated, unless the classification of new entities is assisted computationally. In addition, the ChEBI database is expecting substantial size growth in the next year, so automatic classification, which has up till now not been possible, is urgently required. Automatic classification would also enable the ChEBI ontology classes to be applied to other compound databases such as PubChem. 

*Description Logic Reasoning*
Description logic based reasoning technology is a prime candidate for development of such an automatic classification system as it allows the rules of the classification system to be encoded within the knowledgebase. Already at 18000 entities, ChEBI is a fair size for a real-world application of description logic reasoning technology, and as the ontology is enhanced with a richer density of asserted relationships, the classification will become more complex and challenging. We have successfully tested a description logic-based classification of chemical entities based on specified structural properties using the hypertableaux-based HermiT reasoner, and found it to be sufficiently efficient to be feasible for use in a production environment on a database of the size that ChEBI is now. However, much work still remains to enrich the ChEBI knowledgebase itself with the properties needed to provide the formal class definitions for use in the automated classification, and to assess the efficiency of the available description logic reasoning technology on a database the size of ChEBI's forecast future growth.

*Acknowledgements*
ChEBI is funded by the European Commission under SLING, grant agreement number 226073 (Integrating Activity) within Research Infrastructures of the FP7 Capacities Specific Programme, and by the BBSRC, grant agreement number BB/G022747/1 within the “Bioinformatics and biological resources” fund

Observations Outside the Light-Cone: Algorithms for Non-Equilibrium and Thermal States

We apply algorithms based on Lieb-Robinson bounds to simulate time-dependent and thermal quantities in quantum systems. For time-dependent systems, we modify a previous mapping to quantum circuits to significantly reduce the computer resources required. This modification is based on a principle of "observing" the system outside the light-cone. We apply this method to study spin relaxation in systems started out of equilibrium with initial conditions that give rise to very rapid entanglement growth. We also show that it is possible to approximate time evolution under a local Hamiltonian by a quantum circuit whose light-cone naturally matches the Lieb-Robinson velocity. Asymptotically, these modified methods allow a doubling of the system size that one can obtain compared to direct simulation. We then consider a different problem of thermal properties of disordered spin chains and use quantum belief propagation to average over different configurations. We test this algorithm on one dimensional systems with mixed ferromagnetic and anti-ferromagnetic bonds, where we can compare to quantum Monte Carlo, and then we apply it to the study of disordered, frustrated spin systems.Comment: 19 pages, 12 figure

Tobacco Harm Reduction and Nicotine Containing Products: Research Priorities and Policy Directions

Developments in tobacco harm reduction (HR) and the proliferation of nicotine containing products (NCPs) have important implications for tobaco control (TC). This report sets out a research agenda which will help map and examine these implications

Britain's efforts to reduce smoking are becoming a cash cow for big tobacco

First paragraph: It all began so well. A decade ago a heartfelt concern about the addictiveness of nicotine, and the enormous difficulties this presented for would-be quitters, led to an unprecedented investment in intensive smoking cessation services. Beyond Smoking Kills proudly proclaimed year-on-year increases in funding for stop-smoking services and the establishment of centres throughout the country. Access this article on The Conversation website: https://theconversation.com/britains-efforts-to-reduce-smoking-are-becoming-a-cash-cow-for-big-tobacco-2533

The marketing of e-cigarettes: a quick snapshot

First paragraph: The electronic cigarette (e-cigarette) was launched as a new consumer product in the UK eight years ago.ii Sales now exceed half a million per year and analysts predict the e-cigarette industry, which is worth £150 million in the UK,iii will continue to grow as usage among smokers has more than doubled in two years.iv At present, they are not classed as tobacco products or medicines in the UK and are therefore only regulated under Trading Standards legislation. The situation may change if the health regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), enforces tighter regulations - a decision on whether e-cigarettes require marketing authorisation to prove safety and efficacy is imminent

Testing three hypotheses about effects of sensitive-insensitive parenting on telomeres.

Telomeres are the protective DNA-protein sequences appearing at the ends of chromosomes; they shorten with each cell division and are considered a biomarker of aging. Shorter telomere length and greater erosion have been associated with compromised physical and mental health and are hypothesized to be affected by early life stress. In the latter case, most work has relied on retrospective measures of early life stressors. The Dutch research (n = 193) presented herein tested 3 hypotheses prospectively regarding effects of sensitive-insensitive parenting during the first 2.5 years on telomere length at age 6, when first measured, and change over the following 4 years. It was predicted that (1) less sensitive parenting would predict shorter telomeres and greater erosion and that such effects would be most pronounced in children (2) exposed to prenatal stress and/or (3) who were highly negatively emotional as infants. Results revealed, only, that prenatal stress amplified parenting effects on telomere change-in a differential-susceptibility-related manner: Prenatally stressed children displayed more erosion when they experienced insensitive parenting and less erosion when they experienced sensitive parenting. Mechanisms that might initiate greater postnatal plasticity as a result of prenatal stress are highlighted and future work outlined. (PsycINFO Database Record (c) 2020 APA, all rights reserved)

Promotion of electronic cigarettes: tobacco marketing reinvented?

Electronic cigarettes are not subject to the same marketing controls as tobacco products. Marisa de Andrade, Gerard Hastings, and Kathryn Angus argue that their advertising is likely to appeal to young people and undermine tobacco control policy

Evidence for the disintegration of KIC 12557548 b

Context. The Kepler object KIC 12557548 b is peculiar. It exhibits transit-like features every 15.7 hours that vary in depth between 0.2% and 1.2%. Rappaport et al. (2012) explain the observations in terms of a disintegrating, rocky planet that has a trailing cloud of dust created and constantly replenished by thermal surface erosion. The variability of the transit depth is then a consequence of changes in the cloud optical depth. Aims. We aim to validate the disintegrating-planet scenario by modeling the detailed shape of the observed light curve, and thereby constrain the cloud particle properties to better understand the nature of this intriguing object. Methods. We analysed the six publicly-available quarters of raw Kepler data, phase-folded the light curve and fitted it to a model for the trailing dust cloud. Constraints on the particle properties were investigated with a light-scattering code. Results. The light curve exhibits clear signatures of light scattering and absorption by dust, including a brightening in flux just before ingress correlated with the transit depth and explained by forward scattering, and an asymmetry in the transit light curve shape, which is easily reproduced by an exponentially decaying distribution of optically thin dust, with a typical grain size of 0.1 micron. Conclusions. Our quantitative analysis supports the hypothesis that the transit signal of KIC 12557548 b is due to a variable cloud of dust, most likely originating from a disintegrating object.Comment: 5 pages, 4 figures. Accepted for publication in Astronomy and Astrophysic

Hostage to fortune: an empirical study of the tobacco industry’s business strategies since the advent of e-cigarettes

The tobacco market has been transformed by the arrival of e-cigarettes and array of alternative nicotine delivery systems (ANDS). Public health has struggled to cope with these changes and clear divisions are apparent, but less is known about the tobacco industry (TI) response. This first empirical study to examine TI and independent ANDS companies’ business strategies fills this gap. Primary data were collected through 28 elite interviews with senior/influential TI and independent stakeholders, triangulated with a documentary analysis of company reports, investor analyses, market research, and consultation responses (1022 documents). A deliberately emic analysis shows that tobacco multinationals were initially disconcerted by ANDS, but logic provided by the fiduciary imperative is enabling them to turn a potential threat into profitable opportunities. Interviewees argue market changes played to their strengths: customer links, expertise in nicotine, and enormous financial resources. This enabled portfolio diversification in which combustible and ANDS coexist; providing potential to develop robust scientific and regulatory positions and hope of retrieving corporate reputations. The principal threat for major tobacco players comes from the independent sector, which is prepared and able to satisfy bespoke consumer needs. Multinationals by contrast need to turn ANDS into a genuinely mass-market product appealing to its global customers. They are making progress. Given the continued buoyancy of the combustibles market, they have extensive resources to continue their efforts. Disruptive innovations are not unique to tobacco control. Equivalent technological solutions – with concomitant business opportunities − are emerging in obesity and alcohol fields with implications for public health