Apollo: Democratizing genome annotation.

Genome annotation is the process of identifying the location and function of a genome's encoded features. Improving the biological accuracy of annotation is a complex and iterative process requiring researchers to review and incorporate multiple sources of information such as transcriptome alignments, predictive models based on sequence profiles, and comparisons to features found in related organisms. Because rapidly decreasing costs are enabling an ever-growing number of scientists to incorporate sequencing as a routine laboratory technique, there is widespread demand for tools that can assist in the deliberative analytical review of genomic information. To this end, we present Apollo, an open source software package that enables researchers to efficiently inspect and refine the precise structure and role of genomic features in a graphical browser-based platform. Some of Apollo's newer user interface features include support for real-time collaboration, allowing distributed users to simultaneously edit the same encoded features while also instantly seeing the updates made by other researchers on the same region in a manner similar to Google Docs. Its technical architecture enables Apollo to be integrated into multiple existing genomic analysis pipelines and heterogeneous laboratory workflow platforms. Finally, we consider the implications that Apollo and related applications may have on how the results of genome research are published and made accessible.

The Planteome database: an integrated resource for reference ontologies, plant genomics and phenomics.

The Planteome project (http://www.planteome.org) provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. The Planteome project is developing a plant gene annotation platform; Planteome Noctua, to facilitate community engagement. All the Planteome ontologies are publicly available and are maintained at the Planteome GitHub site (https://github.com/Planteome) for sharing, tracking revisions and new requests. The annotated data are freely accessible from the ontology browser (http://browser.planteome.org/amigo) and our data repository.

Spatially Varying Coefficient Inequalities: Evaluating How the Impact of Patient Characteristics on Breast Cancer Survival Varies by Location.

An increasing number of studies have identified spatial differences in breast cancer survival. However little is known about whether the structure and dynamics of this spatial inequality are consistent across a region. This study aims to evaluate the spatially varying nature of predictors of spatial inequality in relative survival for women diagnosed with breast cancer across Queensland, Australia. All Queensland women aged less than 90 years diagnosed with invasive breast cancer from 1997 to 2007 and followed up to the end of 2008 were extracted from linked Queensland Cancer Registry and BreastScreen Queensland data. Bayesian relative survival models were fitted using various model structures (a spatial regression model, a varying coefficient model and a finite mixture of regressions model) to evaluate the relative excess risk of breast cancer, with the use of Markov chain Monte Carlo computation. The spatially varying coefficient models revealed that some covariate effects may not be constant across the geographic regions of the study. The overall spatial patterns showed lower survival among women living in more remote areas, and higher survival among the urbanised south-east corner. Notwithstanding this, the spatial survival pattern for younger women contrasted with that for older women as well as single women. This complex spatial interplay may be indicative of different factors impacting on survival patterns for these women.

Geographic variation in the intended choice of adjuvant treatments for women diagnosed with screen-detected breast cancer in Queensland.

BACKGROUND: Although early diagnosis and improved treatment can reduce breast cancer mortality, there still appears to be a geographic differential in patient outcomes. This study aims to determine and quantify spatial inequalities in intended adjuvant (radio-, chemo- and hormonal) therapy usage among women with screen-detected breast cancer in Queensland, Australia. METHODS: Linked population-based datasets from BreastScreen Queensland and the Queensland Cancer Registry during 1997-2008 for women aged 40-89 years were used. We adopted a Bayesian shared spatial component model to evaluate the relative intended use of each adjuvant therapy across 478 areas as well as common spatial patterns between treatments. RESULTS: Women living closer to a cancer treatment facility were more likely to intend to use adjuvant therapy. This was particularly marked for radiotherapy when travel time to the closest radiation facility was 4 + h (OR =0.41, 95 % CrI: [0.23, 0.74]) compared to <1 h. The shared spatial effect increased towards the centres with concentrations of radiotherapy facilities, in north-east (Townsville) and south-east (Brisbane) regions of Queensland. Moreover, the presence of residual shared spatial effects indicates that there are other unmeasured geographical barriers influencing women's treatment choices. CONCLUSIONS: This highlights the need to identify the additional barriers that impact on treatment intentions among women diagnosed with screen-detected breast cancer, particularly for those women living further away from cancer treatment centers.

Population attributable risk of modifiable risk factors associated with invasive breast cancer in women aged 45-69 years in Queensland, Australia.

OBJECTIVES: To quantify the population attributable risk of key modifiable risk factors associated with breast cancer incidence in Queensland, Australia. STUDY DESIGN: Population attributable fractions (PAFs) for high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity were calculated, using prevalence data from a representative survey of women attending mammographic screening at BreastScreen Queensland in 2008 and relative risk estimates sourced from published literature. Attributable cancers were calculated using 'underlying' breast cancer incidence data for 2008 based on Poisson regression models, adjusting for the inflation of incidence due to the effects of mammographic screening. MAIN OUTCOME MEASURES: Attributable burden of breast cancer due to high body mass index (BMI), use of hormone replacement therapy (HRT), alcohol consumption and inadequate physical activity. RESULTS: In Queensland women aged 45-69 years, an estimated 12.1% (95% CI: 11.6-12.5%) of invasive breast cancers were attributable to high BMI in post-menopausal women who have never used HRT; 2.8% (95% CI: 2.7-2.9%) to alcohol consumption; 7.6% (95% CI: 7.4-7.9%) to inadequate physical activity in post-menopausal women and 6.2% (95% CI: 5.5-7.0%) to current use of HRT after stratification by BMI and type of HRT used. Combined, just over one quarter (26.0%; 95% CI: 25.4-26.6%) of all invasive breast cancers in Queensland women aged 45-69 years in 2008 were attributable to these modifiable risk factors. CONCLUSIONS: There is benefit in targeting prevention strategies to modify lifestyle behaviours around BMI, physical activity, HRT use and alcohol consumption, as a reduction in these risk factors could decrease invasive breast cancer incidence in the Queensland population.

The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality.

BACKGROUND: This paper presents the latest international descriptive epidemiological data for invasive breast cancer amongst women, including incidence, survival and mortality, as well as information on mammographic screening programmes. RESULTS: Almost 1.4 million women were diagnosed with breast cancer worldwide in 2008 and approximately 459,000 deaths were recorded. Incidence rates were much higher in more developed countries compared to less developed countries (71.7/100,000 and 29.3/100,000 respectively, adjusted to the World 2000 Standard Population) whereas the corresponding mortality rates were 17.1/100,000 and 11.8/100,000. Five-year relative survival estimates range from 12% in parts of Africa to almost 90% in the United States, Australia and Canada, with the differential linked to a combination of early detection, access to treatment services and cultural barriers. Observed improvements in breast cancer survival in more developed parts of the world over recent decades have been attributed to the introduction of population-based screening using mammography and the systemic use of adjuvant therapies. CONCLUSION: The future worldwide breast cancer burden will be strongly influenced by large predicted rises in incidence throughout parts of Asia due to an increasingly "westernised" lifestyle. Efforts are underway to reduce the global disparities in survival for women with breast cancer using cost-effective interventions.

A neural network model of chemotaxis predicts functions of synaptic connections in the nematode Caenorhabditis elegans.

The anatomical connectivity of the nervous system of the nematode Caenorhabditis elegans has been almost completely described, but determination of the neurophysiological basis of behavior in this system is just beginning. Here we used an optimization algorithm to search for patterns of connectivity sufficient to compute the sensorimotor transformation underlying C. elegans chemotaxis, a simple form of spatial orientation behavior in which turning probability is modulated by the rate of change of chemical concentration. Optimization produced differentiator networks capable of simulating chemotaxis. A surprising feature of these networks was inhibitory feedback connections on all neurons. Further analysis showed that feedback regulates the latency between sensory input and behavior. Common patterns of connectivity between the model and biological networks suggest new functions for previously identified connections in the C. elegans nervous system.

Participation in cervical cancer screening by women in rural and remote Aboriginal and Torres Strait Islander communities in Queensland.

OBJECTIVE: To investigate the extent of participation in cervical cancer screening among women who live in discrete rural and remote Indigenous communities in Queensland. DESIGN: Descriptive analysis of data from the Queensland Health Pap Smear Registry for the period March 1999 to February 2001. SUBJECTS: Women aged 20-69 years who had given their address of usual residence as one of 13 discrete rural and remote Indigenous communities in Queensland. MAIN OUTCOME MEASURES: Proportion of women who participated in cervical screening over a two-year period ("biennial participation percentage") and variation in participation across the 13 communities. RESULTS: Overall, the biennial participation percentage in the Indigenous communities was 41.1%. This was 30% lower (risk ratio, 0.70; 95% CI, 0.67-0.72) than that for the rest of Queensland. There was statistically significant variation among communities, with biennial participation percentage ranging from 19.9% to 63.5%. CONCLUSIONS: The variation in participation across the communities suggests that the problem of low participation among Indigenous women is not intractable. Achieving participation rates similar to the highest rates found in our study would be of major benefit to Indigenous women.