However, basic computational skills, data analysis, and stewardship are still rarely taught in researchers tasked with analysing these big datasets. In order to address this skills gap and empower researchers to perform their own data analyses, the Galaxy Training Network (GTN) has previously developed the Galaxy Training Platform (https://training.galaxyproject.org), an open access, community-driven framework training materials for data analysis utilizing the user-friendly Galaxy framework as its primary data analysis platform. Since its inception, this training platform has thrived, with the number of tutorials and contributors growing rapidly, and the range of topics extending beyond life sciences to include topics such as climatology, cheminformatics, and machine learning. While initially aimed at supporting researchers directly, the GTN framework has proven to be an years on adding increased support for this growing community of instructors. New features have been added to facilitate the use of the materials in a classroom setting, simplifying the contribution flow for new materials, and have added a set of train-the-trainer lessons. Here, we present the latest developments in the GTN project, aimed at facilitating the use of the Galaxy Training materials by freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. benefits vitamin d3 , United States of America. Massachusetts, United States of America. following competing interests: DB has a significant financial interest in GalaxyWorks, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and is managed by the Cleveland Clinic. This does not alter our adherence to all the PLOS Computational Biology policies on sharing data and materials. Cervical cancer is a leading cause of cancer-related deaths in women globally and 99% of cases are caused by persistent infection with high-risk strains of the human papillomavirus (HPV). The HPV oncoproteins E6 and E7 establish the cancer phenotype by cooperating with host proteins and identifying them may have important therapeutic benefits. T-box transcription factor 3 (TBX3) is a critical developmental regulator, and when it is overexpressed postnatally, it contributes to several cancers, but little is known about its expression and role in cervical cancer. The current study shows that TBX3 is upregulated in cervical cancer cell lines as well as precancerous and cervical cancer patient tissue and is associated with larger and more invasive tumors. Knockdown and overexpression cell culture models show that TBX3 promotes HPV-positive cell proliferation, migration, and spheroid growth; however, TBX3 inhibits these processes in HPV-negative cells. Importantly, we show that the tumor promoting activity of TBX3 in cervical cancer is dependent on E6/E IMPLICATIONS: In summary, our study highlights the importance of TBX3 as a cooperating partner of E6/E7 in HPV-positive cervical cancer and identifies TBX3 as a potential therapeutic Town and National Health Laboratory Service, Observatory, Cape Town, South BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance. METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group). RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 01; 95% confidence interval (CI), 91-13] and had high discriminatory accuracy (AUC = 73; 95% CI, 71-76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 06 (P < 001) and 14 (P = 05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 001) in the screening-eligible age group. In vitamin d3 benefits -age group it improved the sensitivity by 27% (P = 04) with similar specificity. CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.
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