Path-based systems to guide scientists in the maze of biological data sources

Fueled by novel technologies capable of producing massive amounts of data for a single experiment, scientists are faced with an explosion of information which must be rapidly analyzed and combined with other data to form hypotheses and create knowledge. Today, numerous biological questions can be answered without entering a wet lab. Scientific protocols designed to answer these questions can be run entirely on a computer. Biological resources are often complementary, focused on different objects and reflecting various experts' points of view. Exploiting the richness and diversity of these resources is crucial for scientists. However, with the increase of resources, scientists have to face the problem of selecting sources and tools when interpreting their data. In this paper, we analyze the way in which biologists express and implement scientific protocols, and we identify the requirements for a system which can guide scientists in constructing protocols to answer new biological questions. We present two such systems, BioNavigation and BioGuide dedicated to help scientists select resources by following suitable paths within the growing network of interconnected biological resources.     

Transparent mediation-based access to multiple yeast data sources using an ontology driven interface

BACKGROUND: Saccharomyces cerevisiae is recognized as a model system representing a simple eukaryote whose genome can be easily manipulated. Information solicited by scientists on its biological entities (Proteins, Genes, RNAs...) is scattered within several data sources like SGD, Yeastract, CYGD-MIPS, BioGrid, PhosphoGrid, etc. Because of the heterogeneity of these sources, querying them separately and then manually combining the returned results is a complex and time-consuming task for biologists most of whom are not bioinformatics expert. It also reduces and limits the use that can be made on the available data. RESULTS: To provide transparent and simultaneous access to yeast sources, we have developed YeastMed: an XML and mediator-based system. In this paper, we present our approach in developing this system which takes advantage of SB-KOM to perform the query transformation needed and a set of Data Services to reach the integrated data sources. The system is composed of a set of modules that depend heavily on XML and Semantic Web technologies. User queries are expressed in terms of a domain ontology through a simple form-based web interface. CONCLUSIONS: YeastMed is the first mediation-based system specific for integrating yeast data sources. It was conceived mainly to help biologists to find simultaneously relevant data from multiple data sources. It has a biologist-friendly interface easy to use. The system is available at http://www.khaos.uma.es/yeastmed/.     

Sleeping arrangements and mosquito net use among under-fives: results from the Uganda Demographic and Health Survey

BACKGROUND: The Roll Back Malaria Initiative has identified the under-fives as one of the high risk groups for malaria, and one of the strategies to fight malaria in this group is increasing mosquito net use. This implies that there must be selective targeting at the household level such that the children are protected. However, the Roll Back Malaria preferences must be reconciled with those at the household level to take into account household level preferences. METHODS: This paper is based on the 2000-2001 Uganda Demographic and Health Survey data in which information on mosquito net ownership and use was collected. The patterns of household mosquito net ownership and use for children under five years of age were examined using both bi-variate and multivariate analysis. RESULTS: The preferences at the household level seem to be different; children use mosquito nets primarily because they happen to share a bed with their parents. A child who shares a bed with the mother is 21 times more likely to use a mosquito net than his/her counterpart. CONCLUSION: Increasing mosquito net coverage such that 60% (the target for the RBM) of households have at least one mosquito net will not necessarily protect the under-fives. Either the coverage will have to be expanded or appropriate targeting strategies designed.     

Population Structure of Woody Plants in Relation to Land Use in a Semi‐arid Savanna,West Africa

Indigenous woody species are important natural resources in West African savannas. Information about their population structures and response to human impact, particularly land use, however, is scarce. In this study, we explored (1) the effect of land use on the population structure of woody savanna species; and (2) searched for species with similar population structures related to comparable ecological preferences. Using generalized linear models, we separately analyzed the size‐class distribution (SCD) of 30 species to reveal the influence of three land cover types (non‐arable land, fallows, and protected areas) on population structures. Generalized linear models were applied to identify comparable population structures of species with similar ecological preferences. We were able to identify five groups for shrub species and four groups for tree species with different population structures and comparable ecological preferences. In terms of human impact, we detected four groups of species responding similarly to land use. Especially for trees, we found a strong influence of local land use on SCD and hence, population structures. The SCD of shrub species tends to be more related to species' ecological preferences. Some of the shrub species may be characterized as ubiquitous species as their SCD is neither related to land use nor ecological preferences, indicating a high tolerance to disturbance. The observed results have implications on local woody species composition in relation to land use. According to this, we propose focusing on trees when developing appropriate local land use management strategies.     

Relationships between life-history strategies of European freshwater fish species and their habitat preferences

1. Focusing on the current environmental characteristics, the ‘habitat template’ theory proposes that life‐history strategies summarise how evolution has shaped species to cope with the temporal and spatial variability of their present environment. The hierarchical ‘landscape filters’ concept predicts that the distribution of species reflects their specific traits that allow them to pass through multiple habitat filters. Together, these theories showed the importance of identifying the functional relationships of species to selective habitat forces in order to predict the organisation and response of communities to the environment. 2. We test the relationships between life‐history traits of European freshwater fish species’ and their habitat preferences, to detect the strategies adopted by fish to cope with their current habitat. For this purpose, we use published data on species traits and habitat preferences (microhabitat hydraulics, temperature and oxygen level). We use multivariate analyses to classify fish species’ strategies and test the relationships between strategies and habitat preferences. 3. We identified a continuum of life‐history patterns between two extremes, with opportunistic and periodic species. Our study supports the idea that microhabitat hydraulics plays a more important role as a template for these species ecological strategies than temperature and oxygen level. Indeed, riffle habitats may select opportunistic species whereas weak relationships are found between species strategies and both their temperature and oxygen level preferences. In addition, the ratio between mortality and growth rate (dimensionless trait), reflecting a trade‐off between growth and survival, varied among species according to the use of their hydraulic habitat, with species using deep habitats exhibiting the highest values. 4. These general relationships between hydraulics and traits may be of importance in community ecology to develop predictive models to understand how fish communities change with the hydraulic environment.     

Integration of genomic datasets to predict protein complexes in yeast

The ultimate goal of functional genomics is to define the function of all the genes in the genome of an organism. A large body of information of the biological roles of genes has been accumulated and aggregated in the past decades of research, both from traditional experiments detailing the role of individual genes and proteins, and from newer experimental strategies that aim to characterize gene function on a genomic scale.It is clear that the goal of functional genomics can only be achieved by integrating information and data sources from the variety of these different experiments. Integration of different data is thus an important challenge for bioinformatics.The integration of different data sources often helps to uncover non-obvious relationships between genes, but there are also two further benefits. First, it is likely that whenever information from multiple independent sources agrees, it should be more valid and reliable. Secondly, by looking at the union of multiple sources, one can cover larger parts of the genome. This is obvious for integrating results from multiple single gene or protein experiments, but also necessary for many of the results from genome-wide experiments since they are often confined to certain (although sizable) subsets of the genome.In this paper, we explore an example of such a data integration procedure. We focus on the prediction of membership in protein complexes for individual genes. For this, we recruit six different data sources that include expression profiles, interaction data, essentiality and localization information. Each of these data sources individually contains some weakly predictive information with respect to protein complexes, but we show how this prediction can be improved by combining all of them. Supplementary information is available at http://bioinfo.mbb.yale.edu/integrate/interactions/.Abbreviations: TP: true possitive; TN: true negative; FP: false positive; FN: false negative; Y2H: yeast two-hybrid.     

A Multiple-Pattern Biosequence Analysis Method for Diverse Source Association Mining

BACKGROUND: In order to understand the intricacy of biomolecules more comprehensively, significant patterns extracted from related data collected from diverse sources must be integrated. These data sources may be local or distributed, possibly with different representation schemes. Often, related data from different sources correspond only with respect to some of their values. METHODS: In biological sequence analysis, a goal is to identify new, previously unknown, relevant patterns, to obtain additional insights into the biomolecule. This is known as a pattern discovery task, rather than a pattern matching task. In this research, we present a method to tackle this problem typically found in molecular sequence analysis when the alignment of the sequences is represented as a relation. In this article, we propose an information measure to select attribute values that reflect multiple patterns of significant interdependence information. Based on these selected values, the patterns are evaluated with data values from other sources. RESULTS: In the experiments, a cancer-suppressor gene known as TP53 (encoding tumour protein p53) is analysed with the mutation records of patients. The experiments identify previously unknown points in the molecule that have patterns negatively associated with the occurrence of cancer. CONCLUSION: Since the evaluated interdependence pattern is a global property of the molecule, we conjecture that the identified points might also be a reflection of the molecule's cancer-suppressor characteristics. The experiments also confirm the usefulness of the proposed method.     

Active choice, passive attraction and the cognitive machinery of acoustic preferences

Female preferences for loud calls are widespread among animals that communicate acoustically, but their ‘strategic’ role is still controversial. According to the ‘passive attraction’ hypothesis, females are more likely to respond to loud calls simply because these calls are more effective at stimulating their acoustic receptors and primary neurons. The ‘active choice’ hypothesis, however, assumes that females use sound intensity as a cue to assess the power and location of sound sources and to respond accordingly. To test which hypothesis could best explain the preference for loud calls of female green toads, Bufo viridis, we carried out multitrial discrimination experiments, in which females were given a choice between two stimuli differing in either the power or the distance of their sources or both. In the laboratory, females could discern differences in intensity caused by differences in power or location of the acoustic sources. This ability increased in field experiments, when the speakers and receivers were further apart than in the laboratory experiments. Phonotactic behaviour did not vary significantly between females, but did within females: in their second trial, females were more likely to approach the closer speaker than in the first trial. These findings suggest that sound intensity plays a more complex role in female mate choice than that recognized by the passive attraction hypothesis. To understand female preferences and, ultimately, mate choice, attention should be focused directly on the computational processes of the female's central nervous system.     

An update on microbial carotenoid production: application of recent metabolic engineering tools

Carotenoids are ubiquitous pigments synthesized by plants, fungi, algae, and bacteria. Industrially, carotenoids are used in pharmaceuticals, neutraceuticals, and animal feed additives, as well as colorants in cosmetics and foods. Scientific interest in dietary carotenoids has increased in recent years because of their beneficial effects on human health, such as lowering the risk of cancer and enhancement of immune system function, which are attributed to their antioxidant potential. The availability of carotenoid genes from carotenogenic microbes has made possible the synthesis of carotenoids in non-carotenogenic microbes. The increasing interest in microbial sources of carotenoid is related to consumer preferences for natural additives and the potential cost effectiveness of creating carotenoids via microbial biotechnology. In this review, we will describe the recent progress made in metabolic engineering of non-carotenogenic microorganisms with particular focus on the potential of Escherichia coli for improved carotenoid productivity. Amitabha Das and Sang-Hwal Yoon contributed equally to this work.     

Specialized or opportunistic—how does the high mountain endemic butterfly Erebia nivalis survive in its extreme habitats?

High mountain ecosystems are a challenge for the survival of animal and plant species, which have to evolve specific adaptations to cope with the prevailing extreme conditions. The strategies to survive may reach from opportunistic to highly adapted traits. One species successfully surviving under these conditions is the here studied butterfly Erebia nivalis. In a mark‐release‐recapture study performed in the Hohe Tauern National Park (Austria) from 22 July to 26 August 2013, we marked 1386 individuals and recaptured 342 of these. For each capture event, we recorded the exact point of capture and various other traits (wing conditions, behavior, nectar sources). The population showed a partial protandrous demography with the minority of males emerging prior to the females, but the majority being synchronized with them. Males and females differed significantly in their behavior with males being more flight active and females nectaring and resting more. Both sexes showed preferences for the same plant species as nectar sources, but this specialization apparently is the result of a rapid individual adaptation to the locally available flowers. Estimates of the realized dispersal distances predicted a comparatively high amount of long‐distance flights, especially for females. Therefore, the adaptation of Erebia nivalis to the unpredictable high mountain conditions might be a mixture of opportunism and specialized traits.     

Interhelical angle and distance preferences in globular proteins

Orientational preferences between interacting helices within globular proteins have been studied extensively over the years. A number of classical structural models such as "knobs into holes" and "ridges into grooves" were developed decades ago to explain perceived preferences in interhelical angle distributions. In contrast, relatively recent works have examined statistical biases in angular distributions which result from spherical geometric effects. Those works have concluded that the predictions of classical models are due in large part to these biases. In this article we perform an analysis on the largest set of helix-helix interactions within high-resolution structures of nonhomologous proteins studied to date. We examine the interhelical angle distribution as a function of spatial distance between helix pairs. We show that previous efforts to normalize angle distribution data did not include two important effects: 1), helices can interact with each other in three distinct ways which we refer to as "line-on-line," "endpoint-to-line," and "endpoint-to-endpoint," and each of these interactions has its own geometric effects which must be included in the proper normalization of data; and 2), all normalizations that depend on geometric parameters such as interhelical angle must occur before the data is binned to avoid artifacts of bin size from biasing the conclusions. Taking these two points into account, we find that there are very pronounced preferences for helices to interact at angles of approximately +/-160 and +/-20 degrees in the line-on-line case. This pattern persists when the closest alpha-carbons in the helices vary from 4 to 12 A. The endpoint-to-line and endpoint-to-endpoint cases also exhibit distinct preferences when the data is normalized properly. Analysis of the local structural interactions which give rise to these preferences has not been studied here and is left for future work.     

植物氮形态利用策略及对外来植物入侵性的影响

氮是影响外来植物入侵性的重要因素之一, 但相关研究多关注土壤氮水平的效应, 较少考虑氮形态的作用。为从土壤氮形态利用的角度阐释外来植物的入侵机制, 本文在植物氮形态利用策略分析的基础上, 综述了外来植物氮形态利用的偏好性及其对入侵性的影响。植物的氮形态利用策略有偏好性和可塑性两种, 这可能与植物对土壤氮形态特性的长期适应有关; 植物不仅可以对土壤氮形态做出响应, 而且还能改造土壤氮形态, 并对改变后的土壤氮形态做出反馈响应。很多外来植物入侵硝态氮占优势的干扰生境, 偏好硝态氮的外来植物与本地植物竞争硝态氮; 而偏好铵态氮的外来植物通过抑制土壤硝化作用, 营造铵态氮环境, 促进自身生长, 同时抑制偏好硝态氮的本地植物生长。然而, 植物氮形态利用策略不是一成不变的, 而是受多种生物和非生物因素共同作用影响的复杂过程, 今后应加强多因素交互作用对外来入侵植物氮形态利用策略的影响及机制研究, 更好地揭示氮形态利用策略, 尤其是氮形态利用的可塑性与外来植物入侵性的关系。     

Accuracy of haplotype frequency estimation for biallelic loci, via the expectation-maximization algorithm for unphased diploid genotype data

Haplotype analyses have become increasingly common in genetic studies of human disease because of their ability to identify unique chromosomal segments likely to harbor disease-predisposing genes. The study of haplotypes is also used to investigate many population processes, such as migration and immigration rates, linkage-disequilibrium strength, and the relatedness of populations. Unfortunately, many haplotype-analysis methods require phase information that can be difficult to obtain from samples of nonhaploid species. There are, however, strategies for estimating haplotype frequencies from unphased diploid genotype data collected on a sample of individuals that make use of the expectation-maximization (EM) algorithm to overcome the missing phase information. The accuracy of such strategies, compared with other phase-determination methods, must be assessed before their use can be advocated. In this study, we consider and explore sources of error between EM-derived haplotype frequency estimates and their population parameters, noting that much of this error is due to sampling error, which is inherent in all studies, even when phase can be determined. In light of this, we focus on the additional error between haplotype frequencies within a sample data set and EM-derived haplotype frequency estimates incurred by the estimation procedure. We assess the accuracy of haplotype frequency estimation as a function of a number of factors, including sample size, number of loci studied, allele frequencies, and locus-specific allelic departures from Hardy-Weinberg and linkage equilibrium. We point out the relative impacts of sampling error and estimation error, calling attention to the pronounced accuracy of EM estimates once sampling error has been accounted for. We also suggest that many factors that may influence accuracy can be assessed empirically within a data set-a fact that can be used to create "diagnostics" that a user can turn to for assessing potential inaccuracies in estimation.     

Heterogeneity of Rift Valley fever virus transmission potential across livestock hosts,quantified through a model-based analysis of host viral load and vector infection

Quantifying the variation of pathogens’ life history traits in multiple host systems is crucial to understand their transmission dynamics. It is particularly important for arthropod-borne viruses (arboviruses), which are prone to infecting several species of vertebrate hosts. Here, we focus on how host-pathogen interactions determine the ability of host species to transmit a virus to susceptible vectors upon a potentially infectious contact. Rift Valley fever (RVF) is a viral, vector-borne, zoonotic disease, chosen as a case study. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. Given available data on RVFV competent vectors, we found that, for similar infectious titers, infection rates in the Aedes genus were on average higher than in the Culex genus. Consequently, for Aedes-mediated infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. In lambs, we estimated the overall infectiousness to be 1.93 times higher in individuals which eventually died from the infection than in those recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.     

Recherche de cas médicaux multimodaux à l’aide d’arbres de décision

In this article, we present a Case-based Reasoning system for the retrieval of patient files similar to a case placed as query. We focus on patient files made up of several images with contextual information (such as the patient age, sex and medical history). Indeed, medical experts generally need varied sources of information (which might be incomplete) to diagnose a pathology. Consequently, we derive a retrieval framework from decision trees, which are well suited to process heterogeneous and incomplete information. To be integrated in the system, images are indexed by their digital content. The method is evaluated on a classified diabetic retinopathy database. On this database, results are promising: the retrieval sensitivity reaches 79.5% for a window of five cases, which is almost twice as good as the retrieval of single images alone.     

HIV testing of pregnant women: an ethical analysis

Recent global advances in available technology to prevent mother-to-child HIV transmission necessitate a rethinking of contemporary and previous ethical debates on HIV testing as a means to preventing vertical transmission. In this paper, we will provide an ethical analysis of HIV-testing strategies of pregnant women. First, we argue that provider-initiated opt-out HIV testing seems to be the most effective HIV test strategy. The flip-side of an opt-out strategy is that it may end up as involuntary testing in a clinical setting. We analyse this ethical puzzle from a novel perspective, taking into account the moral importance of certain hypothetical preferences of the child, as well as the moral importance of certain actual preferences of the mother. Finally, we balance the conflicting concerns and try to arrive at an ethically sound solution to this dilemma. Our aim is to introduce a novel perspective from which to analyse testing strategies, and to explore the implications and possible benefits of our proposal. The conclusion from our analysis is that policies that recommend provider-initiated opt-out HIV testing of pregnant mothers, with a risk of becoming involuntary testing in a clinical setting, are acceptable. The rationale behind this is that the increased availability of very effective and inexpensive life-saving drugs makes the ethical problems raised by the possible intrusiveness of HIV testing less important than the child's hypothetical preferences to be born healthy. Health care providers, therefore, have a duty to offer both opt-out HIV testing and available PMTCT (preventing mother-to-child transmission) interventions.     

Living within dynamic social-ecological freshwater systems: System parameters and the role of ecological engineering

The objective of ecological engineering is to design sustainable ecosystems that integrate human communities and their natural environment for the benefit of both. In this paper, we illustrate how social-ecological modeling can be used as a tool to clarify this objective at a landscape scale for freshwater systems. Coupled social-ecological systems (SESs) are open, dynamic systems subject to both ecological and socioeconomic perturbations. Here we demonstrate the interactive effects of social and technological uncertainties on SES dynamics over time. Additionally, we integrate research on ecosystem stability, social-ecological modeling, and ecological engineering to offer guidance for research at the human-environment interface. Based on a case study of Lake Erie's Sandusky watershed, we use an integrated human-biophysical model to investigate the influence of two parameters on SES dynamics: (1) regional societal preferences that impact watershed management and (2) technological innovation that alters agricultural nutrient efficiency. Our results illustrate ways in which SES dynamics and optimum management strategies depend on societal preferences within the region, indicating a key area of uncertainty for future investigation. As guidance for SES restoration, our model results also illustrate the conditions under which technological change that increases nutrient efficiency on farms can and cannot create a win-win, or increase both human welfare and SES resistance to eutrophication simultaneously. Using these results, we elucidate the value of ecological engineering and offer guidance for assessments of ecological engineering projects using social-ecological modeling.