Addressing Challenges in a Graph-Based Analysis of High-Throughput Biological Data

Graph-based methods used in the analysis of DNA microarray technology can be powerful tools in the elucidation of biological relationships. As these methods are developed and applied to various types of data, challenges arise that test the limits of current algorithms. These challenges arise in all phases of data analysis: data normalization, modeling biological networks, and interpreting results. Spectral graph theory methods are investigated as means of threshold selection, a key step in constructing graphical models of biological data. Also important in constructing graphs is the selection of an appropriate gene-gene similarity metric, and an overview of similarity profiles for some biological data sets is present, along with a similarity thresholding method based upon structural properties of random graphs. The identification of altered relationships between two or more conditions is a goal of many microarray gene expression studies. Clique-based methods can identify sets of coexpressed genes within each group, but additional computational methods are required to uncover the differential relationships and sets of genes changing together between groups. Differential filters are reviewed to highlight those changing interactions and sets of changing genes. The effect of various normalization methods on these differential results is also studied. Finally, how methods commonly used in the analysis of gene expression data can be used to investigate relationships in noisy and incomplete historical ecosystem data is explored

NBT (No-Boundary Thinking): Needed To Attend To Ethical Implications Of Data And AI

In this era of Big Data and AI, expertise in multiple aspects of data, computing, and the domains of application is needed. This calls for teams of experts with different training and perspectives. Because data analysis can have serious ethical implications, it is important that these teams are well and deeply integrated. No-Boundary Thinking (NBT) teams can provide support for team formation and maintenance, thereby attending to the many dimensions of the ethics of data and analysis. In this NBT workshop session, we discuss the ethical concerns that arise from the use of data and AI, and the implications for team building; and provide and brainstorm suggestions for ethical data enabled science and AI

Team Building Without Boundaries

Team building can be challenging when participants are from the same discipline or sub-discipline, but needs special attention when participants use a different vocabulary and have different cultural views on what constitutes viable problems and solutions. Essential to No Boundary Thinking (NBT) teams is proper formulation of the problem to be solved, and a basic tenant is that the NBT team must come together with diverse perspectives to decide the problem before solutions can be considered. Given that participants come with different views on problem formulation and solution, it is important to consider a robust process for team formation and maintenance. This takes extra effort and time, but scholars studying teams of experts with diverse training have found that they are better positioned to be successful in solving even deep and difficult problems especially if they have learned to work well with each other. At this workshop we will discuss principles that scholars who have worked in NBT teams have discovered as effective. We will then engage with the workshop participants to consider discuss these principles and brainstorm to consider other approaches

Assessing the early influence of COVID-19 in an analysis of the immediate implementation of Minimum Pricing for Alcohol on drinkers in Wales

Background: The Welsh Government has commissioned a number of projects to consider the influence their implementation of Minimum Pricing for Alcohol (MPA) legislation in March 2020 had on the alcohol consumption and related behaviours of drinkers. Given the MPA's overlap with the COVID-19 pandemic and its related lockdown measures and restrictions, this rapidly became a story about the early impact of COVID-19 as it did MPA. This paper captures the core thematic messages from this specific strand of work, and in doing so reflects on (1) how early experiences of COVID-19 and the first lockdown influenced consumption and purchasing of alcohol behaviours and, in turn, (2) how relevant the introduction of MPA was for any of these. Methods: Semi-structured interviews were conducted by telephone with 32 drinkers 9 months after the implementation of the legislation in March 2020. The sample was recruited from three sources: the National Survey for Wales; a third sector organisation offering housing support to the homeless; and through an online survey on MPA. Results: COVID-19 had more relevance than MPA to drinkers. Furthermore, when MPA did have an influence on their behaviour, it was felt most keenly by the harmful drinkers in the study. These drinkers described spending more on alcohol, switching to other potentially more harmful substances, such as crack cocaine and synthetic cannabinoids, and more involvement in acquisitive crime and begging after the price increase. While our results might be an early indication of the influence of MPA on harmful drinkers, the small sample of this group in our study limits the generalisability of the findings. Conclusion: To date, the implementation of MPA has had little influence on the drinking patterns or lives of the drinkers in our sample. It is important that future research examines the longer-term influences of MPA before any conclusions on its effectiveness can be drawn

Applying predator-prey theory to modelling immune-mediated, within-host interspecific parasite interactions

Predator-prey models are often applied to the interactions between host immunity and parasite growth. A key component of these models is the immune system's functional response, the relationship between immune activity and parasite load. Typically, models assume a simple, linear functional response. However, based on the mechanistic interactions between parasites and immunity we argue that alternative forms are more likely, resulting in very different predictions, ranging from parasite exclusion to chronic infection. By extending this framework to consider multiple infections we show that combinations of parasites eliciting different functional responses greatly affect community stability. Indeed, some parasites may stabilize other species that would be unstable if infecting alone. Therefore hosts' immune systems may have adapted to tolerate certain parasites, rather than clear them and risk erratic parasite dynamics. We urge for more detailed empirical information relating immune activity to parasite load to enable better predictions of the dynamic consequences of immune-mediated interspecific interactions within parasite communities

Adapting existing behaviour: perceptions of substance switching and implementation of minimum pricing for alcohol in Wales

Minimum Pricing for Alcohol (MPA) was enacted in Wales on March 2nd 2020. During the legislative process (i.e. consultation and parliamentary discussion), concern was expressed about the possibility of some drinkers switching to using other substances in response to any rise in the cost of alcohol. This paper reports on findings from a study which explored these pre-implementation concerns and how the policy was shaped. The research involved surveys (n=193) and interviews (n=87) with drinkers (predominantly harmful or treatment seeking) and providers of services. Survey responses were detailed, thus when combined with the interviews, provided a wealth of qualitative data, which are drawn upon in this paper. The findings highlight an expectation that most drinkers would respond to the new policy with adaptations of their coping mechanisms to maintain alcohol use at pre-legislative levels. This was either by switching alcohol products and adjusting their lifestyle to maintain an affordable drinking habit or developing new behaviours to manage additional costs. A small group of those with previous experience of drug use were identified as likely to switch from using alcohol to some other substances. Prior to the legislation being implemented awareness of the detail of the policy was found to be low, and perceptions of increased potential harm for certain groups were linked to concern about a lack of treatment capacity

Weather, Not Climate, Defines Distributions of Vagile Bird Species

Background\ud \ud Accurate predictions of species distributions are essential for climate change impact assessments. However the standard practice of using long-term climate averages to train species distribution models might mute important temporal patterns of species distribution. The benefit of using temporally explicit weather and distribution data has not been assessed. 1We hypothesized that short-term weather associated with the time a species was recorded should be superior to long-term climate measures for predicting distributions of mobile species.\ud \ud Methodology\ud \ud We tested our hypothesis by generating distribution models for 157 bird species found in Australian tropical savannas (ATS) using modelling algorithm Maxent. The variable weather of the ATS supports a bird assemblage with variable movement patterns and a high incidence of nomadism. We developed “weather” models by relating climatic variables (mean temperature, rainfall, rainfall seasonality and temperature seasonality) from the three month, six month and one year period preceding each bird record over a 58 year period (1950–2008). These weather models were compared against models built using long-term (30 year) averages of the same climatic variables.\ud \ud Conclusions\ud \ud Weather models consistently achieved higher model scores than climate models, particularly for wide-ranging, nomadic and desert species. Climate models predicted larger range areas for species, whereas weather models quantified fluctuations in habitat suitability across months, seasons and years. Models based on long-term climate averages over-estimate availability of suitable habitat and species' climatic tolerances, masking species potential vulnerability to climate change. Our results demonstrate that dynamic approaches to distribution modelling, such as incorporating organism-appropriate temporal scales, improves understanding of species distributions

Assessing the early influence of COVID-19 in an analysis of the immediate implementation of Minimum Pricing for Alcohol on drinkers in Wales

Background: The Welsh Government has commissioned a number of projects to consider the influence their implementation of Minimum Pricing for Alcohol (MPA) legislation in March 2020 had on the alcohol consumption and related behaviours of drinkers. Given the MPA's overlap with the COVID-19 pandemic and its related lockdown measures and restrictions, this rapidly became a story about the early impact of COVID-19 as it did MPA. This paper captures the core thematic messages from this specific strand of work, and in doing so reflects on (1) how early experiences of COVID-19 and the first lockdown influenced consumption and purchasing of alcohol behaviours and, in turn, (2) how relevant the introduction of MPA was for any of these. Methods: Semi-structured interviews were conducted by telephone with 32 drinkers 9 months after the implementation of the legislation in March 2020. The sample was recruited from three sources: the National Survey for Wales; a third sector organisation offering housing support to the homeless; and through an online survey on MPA. Results: COVID-19 had more relevance than MPA to drinkers. Furthermore, when MPA did have an influence on their behaviour, it was felt most keenly by the harmful drinkers in the study. These drinkers described spending more on alcohol, switching to other potentially more harmful substances, such as crack cocaine and synthetic cannabinoids, and more involvement in acquisitive crime and begging after the price increase. While our results might be an early indication of the influence of MPA on harmful drinkers, the small sample of this group in our study limits the generalisability of the findings. Conclusion: To date, the implementation of MPA has had little influence on the drinking patterns or lives of the drinkers in our sample. It is important that future research examines the longer-term influences of MPA before any conclusions on its effectiveness can be drawn

Crystal structure of zinc-α2-glycoprotein in complex with a fatty acid reveals multiple different modes of protein-lipid binding

Human zinc-α2-glycoprotein (ZAG) is a 42 kDa adipokine which regulates body fat mass and is associated with cachexia and obesity. ZAG belongs to the major histocompatibility complex class I protein family and binds long chain polyunsaturated fatty acids in its groove formed from the α1 and α2 domains. To identify the molecular basis of its lipid-binding function, we determined the first crystal structure at 2.49Å resolution for fatty acid-bound ZAG, where the ligand was the fluorescent 11-(dansylamino)undecanoic acid (DAUDA). The 192 kDa crystallographic asymmetric unit contained six ZAG and eight fatty acid molecules in unique conformations. Six fatty acid molecules were localised to the ZAG grooves, where its tails were bound in two distinct conformations. The carboxylate groups of three fatty acids projected out of the groove, while the fourth was hydrogen bonded with R73 inside the groove. Other ligand-residue contacts were primarily hydrophobic. A new fatty acid site was revealed for two further DAUDA molecules at the ZAG α3 domains. Following conformational changes from unbound ZAG, the α3 domains formed tetrameric β-barrel structures lined by fatty acid molecules that doubled the binding capacity of ZAG. Analytical ultracentrifugation revealed that ZAG in solution was a monomer in the absence of DAUDA, but formed small amounts of tetramers with DAUDA. By showing that ZAG binds fatty acids in different locations, we demonstrate an augmented mechanism for fatty acid binding in ZAG that is distinct from other known fatty acid binding proteins, and may be relevant to cachexia