Human papillomavirus associated oropharyngeal cancer now the most common mucosal head and neck cancer in Queensland.

INTRODUCTION: The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population-based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV-associated disease. METHODS: This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age-standardised rates (ASR) (3-year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2- and 5-year overall survival. RESULTS: There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy-seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2- and 5- year overall survival of 89% and 79%, respectively. CONCLUSION: OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV-associated (p16+), presenting with early-stage disease with a favourable prognosis.

Utility of 30-day mortality as a quality metric for palliative radiation treatment: A population-based analysis from Queensland, Australia.

INTRODUCTION: Palliative radiotherapy (PRT) is frequently used to treat symptoms of advanced cancer, however benefits are questionable when life expectancy is limited. The 30-day mortality rate after PRT is a potential quality indicator, and results from a recent meta-analysis suggest a benchmark of 16% as an upper limit. In this population-based study from Queensland, Australia, we examined 30-day mortality rates following PRT and factors associated with decreased life expectancy. METHODS: Retrospective population data from Queensland Oncology Repository was used. Study population data included 22,501 patients diagnosed with an invasive cancer who died from any cause between 2008 and 2017 and had received PRT. Thirty-day mortality rates were determined from the date of last PRT fraction to date of death. Cox proportional hazards models were used to identify factors independently associated with risk of death within 30 days of PRT. RESULTS: Overall 30-day mortality after PRT was 22.2% with decreasing trend in more recent years (P = 0.001). Male (HR = 1.20, 95% CI = 1.13-1.27); receiving 5 or less radiotherapy fractions (HR = 2.97, 95% CI = 2.74-3.22 and HR = 2.17, 95% CI = 2.03-2.32, respectively) and receiving PRT in a private compared to public facility (HR = 1.61, 95% CI = 1.51-1.71) was associated with decreased survival. CONCLUSION: The 30-day mortality rate in Queensland following PRT is higher than expected and there is scope to reduce unnecessarily protracted treatment schedules. We encourage other Australian and New Zealand centres to examine and report their own 30-day mortality rate following PRT and would support collaboration for 30-day mortality to become a national and international quality metric for radiation oncology centres.

End-of-life intravenous chemotherapy administration patterns in the treatment of Queensland lung and pancreas cancer patients: a 10-year retrospective analysis.

BACKGROUND: End-of-life (EOL) chemotherapy administration rates for solid tumours are 12-20% and are associated with a reduced quality of life, increased hospitalisation and incidence of death within an acute care facility. AIM: We sought to determine the rate of EOL chemotherapy in government and private hospitals and determine the impact on hospitalisations and location of death in lung and pancreatic cancer patients. METHODS: Data were obtained from the Queensland Oncology Repository between 2005 and 2014. Lung (n = 16 501) and pancreatic cancer (n = 4144) deaths were analysed. EOL chemotherapy was determined to be within 30 days of death. Demographics, location of treatment and death are reported. RESULTS: Chemotherapy was administered to 6518 (40%) lung cancer and 1694 (41%) pancreatic cancer patients. A total of 1474 (9%) and 477 (12%) patients, respectively, received EOL chemotherapy. EOL chemotherapy was more common in males and those with distant metastatic disease, while less likely in the elderly and those with a lower socioeconomic status. EOL chemotherapy was more prevalent in large hospitals and was more common in private compared with government hospitals for pancreatic cancer (30 vs 26%; P < 0.001), while it was similar for lung cancer (24 vs 22%; P = 0.115). Death after EOL chemotherapy compared with all cancer deaths was more common in an acute care facility (lung cancer: 60 vs 37%; P < 0.001; pancreatic cancer: 53 vs 36%; P < 0.001). CONCLUSIONS: EOL chemotherapy rates were similar to Australian yet marginally lower than international rates, with variation dependent on the size and type of facility and increased the rate of deaths within an acute care facility.

Development and implementation of a population-based breast cancer quality index in Queensland, Australia.

BACKGROUND: While quality indicators (QI) are relatively commonplace, QIs focusing on breast cancer treatment and outcomes have not been previously developed in Australia. We describe the development and implementation of the Queensland Breast Cancer Quality Index (BCQI) and report on trends in performance indicators over time. METHODS: Development of the BCQI was overseen by a clinician-led quality assurance committee covering several clinical disciplines. Using a population-based dataset of female patients diagnosed with breast cancer from 2007 to 2016 (n = 27,541) we examined trends in indicators over time. RESULTS: The BCQI includes two quality dimensions (Effective and Accessible) and 14 indicators for public and private cancer services. Rates of re-excision following breast conservation surgery (BCS) and conversion of BCS to mastectomy reduced over time (p < 0.001 and p = 0.005, respectively). BCS was less common for women living outside a major city (p < 0.001), who had their surgery in a public (p < 0.001) or low volume hospital (p < 0.001). CONCLUSIONS: Application of the BCQI at a population-level demonstrated our results are comparable to, and in some cases superior to other jurisdictions. We identified some areas where improvement over time has occurred, while also identifying some outcomes requiring further investigation. POLICY SUMMARY: The BCQI is a well-established and valuable tool for measuring and monitoring breast cancer care. Practice indicators provide useful information to assist with identifying services performing well as well as those that may benefit from improvement.

Breast-cancer mortality in screened versus unscreened women: Long-term results from a population-based study in Queensland, Australia.

OBJECTIVE: In the context of a mature mammographic screening programme, the aim of this population-based study was to estimate rates of breast-cancer mortality among participants versus non-participants in Queensland, Australia. METHODS: The Queensland Electoral Roll was used to identify women aged 50-65 in the year 2000 (n = 269,198). Women with a prior history of invasive or in situ breast cancer were excluded (n = 6,848). The study population was then linked to mammography records from BreastScreen Queensland together with the Wesley Breast Screening Clinic (the largest provider of private screening in Queensland) to establish a screened cohort (n = 187,558) and an unscreened cohort (n = 74,792). Cohort members were matched and linked to cancer notifications and deaths through the state-based Queensland Oncology Repository. Differences in breast-cancer mortality between the two cohorts were measured using Cox proportional hazards regression. RESULTS: After 16 years of follow-up, women in the screened cohort showed a 39% reduction in breast-cancer mortality compared to the unscreened cohort (HR = 0.61, 95%CI = 0.55-0.68). Cumulative mortality over the same period was 0.47% and 0.77% in the screened and unscreened cohorts, respectively. CONCLUSIONS: This study found a significant reduction in breast-cancer mortality for women who participated in mammographic screening compared to unscreened women. Our findings of a breast-cancer mortality benefit for women who have mammographic screening are in line with other observational studies.

Cancer Incidence, Mortality, and Survival for Children, Adolescents, and Young Adults in Queensland Between 1987 and 2016.

Purpose: Cancer remains the most common cause of disease-related death among young people and carries a significant burden. In the absence of prior state-based Australian epidemiological studies, this retrospective cohort study reviewed all cases of invasive cancer diagnosed in Queensland children, adolescents, and young adults (AYAs) (0-39 years) from 1987 to 2016 using the Queensland Oncology Repository (QOR). Methods: Cancers were classified according to Surveillance, Epidemiology and End Results (SEER) AYA site recode. Age-standardized rates (ASRs) were calculated. JoinPoint regression examined trends in ASRs across three age cohorts, for three decades (1987-1996, 1997-2006, and 2007-2016). Results: In total, 3,576 children aged 0-14 years (ASR = 15.2/100,000), 6,441 aged 15-24 years (ASR = 39.3/100,000), and 29,923 (ASR = 122.6/100,000) aged 25-39 years were diagnosed. Incidence increased for female children, and leukemia was the most common diagnosis. For those 15-24 years, incidence increased initially before decreasing and was higher than other nationally reported rates. For those 25-39 years, incidence increased. For the older cohorts, the most common diagnosis was melanoma. All cohorts demonstrated a decline in mortality and improvement in 5-year relative survival, with those 0-14 years demonstrating the greatest gains. The lowest survival for all cohorts was associated with central nervous system tumors. Conclusion: These results highlight areas in need of further investigation to improve survival, reduce the burden of cancer for young people, and aid service delivery. Future studies should focus on cancer biology, early detection, barriers in access to clinical trials, innovative models of care, improved data collection, and patient-reported outcomes.

Regional nodal metastasis and 5-year survival in patients with thin melanoma in Queensland: a population-based study.

BACKGROUND: Optimal management of regional lymph nodes for thin cutaneous melanoma is uncertain. We evaluated regional lymph node involvement and 5-year melanoma-specific survival (MSS) in patients with thin (≤1 mm) primary melanoma. METHODS: Patients with a melanoma, American Joint Committee on Cancer Staging 8th Edition pT1a (<0.8 mm) or pT1b (ulceration; and/or 0.8-1.0 mm), diagnosed during 2001-2015 were identified from the Queensland Oncology Repository. We extracted demographic, pathology and clinical details, including sentinel lymph node biopsy (SLNB), regional nodal dissection and nodal recurrence. Poisson regression was used to assess recurrence risk in patients who did not undergo SLNB. The 5-year MSS was calculated using the Kaplan-Maier method with Cox regression to compare survival outcomes according to SLNB performance. RESULTS: Of the 27 824 eligible patients, 240 (0.9%) underwent SLNB. One hundred and seventy-eight patients (0.6%) without SLNB had nodal recurrence. Of the 4848 patients with a pT1b lesion, 166 (3.4%) had SLNB with 12 (7.2%) positive; of the remainder, 99 (2.1%) had clinical recurrence. Risk of recurrence was higher in males, nodular subtype and T1b lesions and lower if patients were aged >60 years. The 5-year MSS was similar for observed and SLNB cohorts (99.66% versus 98.92%) but worse for T1b lesions (98.90%) and clinical nodal recurrence (66.89%). CONCLUSION: Overall prognosis for T1 melanoma is excellent with nodal involvement being rare. However, the American Joint Committee on Cancer 8th Edition T1b melanoma correlates with significantly worse 5-year MSS and increased regional nodal recurrence (notably for 0.8-1.0 mm lesions with ulceration). Further characterization of high-risk groups for nodal positivity that impacts patient outcome is needed for the pT1 melanoma cohort.

Trends in myeloma relative survival in Queensland by treatment era, age, place of residence, and socioeconomic status.

Relative survival (RS) in myeloma has improved in younger but not older patients (≥80 years) with treatment advances. Whether place of residence or socioeconomic status (SES) affect RS is unknown. We used the Queensland cancer registry to calculate the five-year RS of myeloma patients diagnosed between 1982 and 2014. This period was divided into three eras: (1) 1982-1995 chemotherapy alone; (2) 1996-2007 autologous stem cell transplantation; (3) 2008-2014 novel agents (proteasome inhibitors and IMIDs). 6025 patients were diagnosed from 1982 to 2014. RS improved across eras: (1) 30% vs. (2) 43% vs. (3) 53% (p < .001 (2) vs. (1); p < .001 (3) vs. (2)). RS improved across all age groups, including patients ≥80 years. Patients with disadvantaged SES (39% vs. affluent 46%; p < .001) and rural patients (40% vs. urban 45%; p < .001) had an inferior RS. RS has improved across all ages with treatment advances.

The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species.

In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven't been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics.

Nonbreast cancer incidence, treatment received and outcomes: Are there differences in breast screening attendees versus nonattendees?

While reductions in breast cancer mortality have been evident since the introduction of population-based breast screening in women aged 50-74 years, participation in cancer screening programs can be influenced by several factors, including health system and those related to the individual. In our study, we compared cancer incidence and mortality for several cancer types other than breast cancer, noncancer mortality and patterns of treatment amongst women who did and did not participate in mammography screening. All women aged 50-65 years enrolled on the Queensland Electoral Roll in 2000 were included. The study population was then linked to records from the population-based breast screening program and private fee-for-service screening options to establish screened and unscreened cohorts. Diagnostic details for selected cancers and cause of death were obtained from the Queensland Oncology Repository. We calculated incidence rate ratios and hazard ratios comparing screened and unscreened cohorts. Among screened compared to unscreened women, we found a lower incidence of cancers of the lung, cervix, head and neck and esophagus and an increase in colorectal cancers. Cancer mortality (excluding breast cancer) was 35% lower among screened compared to unscreened women and they were also about 23% less likely to be diagnosed with distant disease. Screened compared to unscreened women were more likely to receive surgery and less likely to receive no treatment. Our study adds further to the population data examining outcomes among women participating in mammography screening.

Epidemiological trends of neuroendocrine tumours over three decades in Queensland, Australia.

INTRODUCTION: While neuroendocrine tumours (NETs) account for only a small proportion of cancer diagnoses, incidence has been rising over time. We examined incidence, mortality and survival over three decades in a large population-based registry study. METHODS: This retrospective study included all cases (n = 4580) of NETs diagnosed from 1986 to 2015 in Queensland, Australia. We examined directly age-standardised incidence and mortality rates. The impact on overall survival according to demographic factors and primary site was modelled using multivariable Cox proportional hazards regression (HR). Cause-specific and relative survival were estimated using the Kaplan-Meier survival function. RESULTS: Annual incidence increased from 2.0 in 1986 to 6.3 per 100,000 in 2015, while mortality remained stable. The most common primary site was appendix followed by lung, small intestine and rectum. Rectal, stomach, appendiceal and pancreatic NETs had the greatest rate increase, while lung NETs decreased over the same period. Five-year cause-specific survival improved from 69.4% during 1986-1995 to 92.6% from 2006 to 2015. Survival was highest for appendiceal and rectal NETs and lowest for pancreas and unknown primary sites. The risk of dying within five years of diagnosis was about 40% higher for males (HR = 1.41, 95%CI 1.20-1.65) and significantly higher for patients aged over 40 years compared to younger patients (p < 0.001). CONCLUSION: This study, including 30 years of data, found significantly increasing rates of NETs and confirms results from elsewhere. Increasing survival over time in this study, likely reflects increased awareness, improvements in diagnostic imaging, greater use of endoscopy and colonoscopy, and the development of new therapies.

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.

AgBioData consortium recommendations for sustainable genomics and genetics databases for agriculture.

The future of agricultural research depends on data. The sheer volume of agricultural biological data being produced today makes excellent data management essential. Governmental agencies, publishers and science funders require data management plans for publicly funded research. Furthermore, the value of data increases exponentially when they are properly stored, described, integrated and shared, so that they can be easily utilized in future analyses. AgBioData (https://www.agbiodata.org) is a consortium of people working at agricultural biological databases, data archives and knowledgbases who strive to identify common issues in database development, curation and management, with the goal of creating database products that are more Findable, Accessible, Interoperable and Reusable. We strive to promote authentic, detailed, accurate and explicit communication between all parties involved in scientific data. As a step toward this goal, we present the current state of biocuration, ontologies, metadata and persistence, database platforms, programmatic (machine) access to data, communication and sustainability with regard to data curation. Each section describes challenges and opportunities for these topics, along with recommendations and best practices.

Relative survival of patients with lymphoma in Queensland according to histological subtype.

OBJECTIVE: To evaluate relative survival of patients in Queensland with different lymphoma subtypes; to determine whether outcomes have improved with recent changes in treatment; to evaluate relative survival according to place of residence and socio-economic status. DESIGN: Retrospective population-based study; analysis of data from the Oncology Analysis System, an online reporting tool for cancer incidence and outcomes in Queensland. PARTICIPANTS: Patients over 15 years of age diagnosed with lymphoma in Queensland during 1993-2012. MAIN OUTCOME MEASURES: Relative survival by lymphoma subtype; influence of place of residence and socio-economic status, age group, sex, year of diagnosis (in 5-year bands), and Pharmaceutical Benefits Scheme funding of rituximab for treating B-cell lymphomas on relative survival. RESULTS: 9509 people (56% men) were diagnosed with lymphoma during 1993-2012. Five-year relative survival improved significantly between 1993-1997 and 2008-2012 for patients with diffuse large B-cell lymphoma (47%; 95% CI, 42-51% v 64%; 95% CI, 61-67%) or follicular lymphoma (62%; 95% CI, 57-66% v 88%; 95% CI, 85-90%; each P < 0.001). Rituximab became available for treating these subtypes during 2003-2006. There was no change in relative survival for patients with Hodgkin lymphoma (81%; 95% CI, 76-85% v 80%; 95% CI, 75-84%; P = 0.22). The only statistically significant difference according to place of residence or socio-economic status was inferior relative survival for rural residents with diffuse large B-cell lymphoma (hazard ratio, 1.14; 95% CI, 1.01-1.28). CONCLUSION: Relative survival for patients with B-cell non-Hodgkin lymphoma improved significantly with the introduction of rituximab as first-line therapy in Australia.

To stent or not to stent: the use of transanastomotic biliary stents in liver transplantation and patient outcomes.

BACKGROUND: There is no substantial evidence for the use of biliary stents in bile duct reconstruction during liver transplantation. METHOD: A longitudinal, retrospective cohort study was performed to compare biliary complications between stented and non-stented patients between 2011 and 2015 at the Princess Alexandra Hospital, Brisbane, Australia. RESULTS: We found no significant difference in biliary complications between stented and non-stented groups. Stented patients were 3.31 times as likely to require subsequent intervention, mainly in the form of stent removal. CONCLUSION: These results suggest that there is limited benefit in the placement of endobiliary stents in liver transplantation. Given that this was purely an observational study, causality cannot be proven and a prospective cohort trial would be beneficial in further defining these relationships.

NovoGraph: Human genome graph construction from multiple long-read de novo assemblies.

Genome graphs are emerging as an important novel approach to the analysis of high-throughput human sequencing data. By explicitly representing genetic variants and alternative haplotypes in a mappable data structure, they can enable the improved analysis of structurally variable and hyperpolymorphic regions of the genome. In most existing approaches, graphs are constructed from variant call sets derived from short-read sequencing. As long-read sequencing becomes more cost-effective and enables de novo assembly for increasing numbers of whole genomes, a method for the direct construction of a genome graph from sets of assembled human genomes would be desirable. Such assembly-based genome graphs would encompass the wide spectrum of genetic variation accessible to long-read-based de novo assembly, including large structural variants and divergent haplotypes. Here we present NovoGraph, a method for the construction of a human genome graph directly from a set of de novo assemblies. NovoGraph constructs a genome-wide multiple sequence alignment of all input contigs and creates a graph by merging the input sequences at positions that are both homologous and sequence-identical. NovoGraph outputs resulting graphs in VCF format that can be loaded into third-party genome graph toolkits. To demonstrate NovoGraph, we construct a genome graph with 23,478,835 variant sites and 30,582,795 variant alleles from de novo assemblies of seven ethnically diverse human genomes (AK1, CHM1, CHM13, HG003, HG004, HX1, NA19240). Initial evaluations show that mapping against the constructed graph reduces the average mismatch rate of reads from sample NA12878 by approximately 0.2%, albeit at a slightly increased rate of reads that remain unmapped.

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.

Patterns of care for ductal carcinoma in situ of the breast: Queensland's experience over a decade.

OBJECTIVES: To review management of ductal carcinoma in situ (DCIS) of the breast in Queensland, with reference to breast conserving surgery (BCS) and adjuvant radiation therapy (RT). In addition, we examined the incidence of invasive breast cancer recurrence and factors predictive of invasive recurrence. MATERIALS AND METHODS: A retrospective review of the Queensland Oncology Repository identified women with resected DCIS (TisN0) ± adjuvant RT between 2003 and 2012. Time to invasive breast cancer recurrence was analysed using the Kaplan Meier method. Median follow-up was 4.9 years. RESULTS: 3038 women had surgery. 940 (31%) had mastectomy and 2098 (69%) underwent BCS. Of 2098 women having BCS, 1100 (52%) received BCS alone and 998(48%) received adjuvant RT. The use of RT significantly increased over the decade from 25% to 62% (p=<0.001). Clinicopathological factors associated with RT use on multivariate analysis included age ≤70, higher socioeconomic status, larger tumour size, higher nuclear grade and surgical margins ≤5 mm. Invasive breast cancer recurrence at 5 years was 1.7% [95% CI 1.0-3.0] in RT group versus 2.8% [95% CI 2.1-3.8] in BCS alone group. Factors associated with increased risk of invasive recurrence on multivariate analysis were age <40 and surgical margins ≤2 mm. CONCLUSION: The use of adjuvant RT in Queensland significantly increased between 2003 and 2012. Selection of patients for RT was based on clinicopathological factors associated with higher recurrence risk. Although longer follow-up is required, the selective use of radiation therapy after BCS is associated with a low rate of invasive breast cancer recurrence at 5 years.

WikiGenomes: an open web application for community consumption and curation of gene annotation data in Wikidata.

With the advancement of genome-sequencing technologies, new genomes are being sequenced daily. Although these sequences are deposited in publicly available data warehouses, their functional and genomic annotations (beyond genes which are predicted automatically) mostly reside in the text of primary publications. Professional curators are hard at work extracting those annotations from the literature for the most studied organisms and depositing them in structured databases. However, the resources don't exist to fund the comprehensive curation of the thousands of newly sequenced organisms in this manner. Here, we describe WikiGenomes (wikigenomes.org), a web application that facilitates the consumption and curation of genomic data by the entire scientific community. WikiGenomes is based on Wikidata, an openly editable knowledge graph with the goal of aggregating published knowledge into a free and open database. WikiGenomes empowers the individual genomic researcher to contribute their expertise to the curation effort and integrates the knowledge into Wikidata, enabling it to be accessed by anyone without restriction. Database URL: www.wikigenomes.org.

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species.

The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype-phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.