Designing the Australian Cancer Atlas: visualizing geostatistical model uncertainty for multiple audiences.

OBJECTIVE: The Australian Cancer Atlas (ACA) aims to provide small-area estimates of cancer incidence and survival in Australia to help identify and address geographical health disparities. We report on the 21-month user-centered design study to visualize the data, in particular, the visualization of the estimate uncertainty for multiple audiences. MATERIALS AND METHODS: The preliminary phases included a scoping study, literature review, and target audience focus groups. Several methods were used to reach the wide target audience. The design and development stage included digital prototyping in parallel with Bayesian model development. Feedback was sought from multiple workshops, audience focus groups, and regular meetings throughout with an expert external advisory group. RESULTS: The initial scoping identified 4 target audience groups: the general public, researchers, health practitioners, and policy makers. These target groups were consulted throughout the project to ensure the developed model and uncertainty visualizations were effective for communication. In this paper, we detail ACA features and design iterations, including the 3 complementary ways in which uncertainty is communicated: the wave plot, the v-plot, and color transparency. DISCUSSION: We reflect on the methods, design iterations, decision-making process, and document lessons learned for future atlases. CONCLUSION: The ACA has been hugely successful since launching in 2018. It has received over 62 000 individual users from over 100 countries and across all target audiences. It has been replicated in other countries and the second version of the ACA was launched in May 2024. This paper provides rich documentation for future projects.

Highly efficient CRISPR/HDR-mediated knock-in for mouse embryonic stem cells and zygotes.

The clustered regularly interspaced short palindromic repeat (CRISPR) gene editing technique, based on the non-homologous end-joining (NHEJ) repair pathway, has been used to generate gene knock-outs with variable sizes of small insertion/deletions with high efficiency. More precise genome editing, either the insertion or deletion of a desired fragment, can be done by combining the homology-directed-repair (HDR) pathway with CRISPR cleavage. However, HDR-mediated gene knock-in experiments are typically inefficient, and there have been no reports of successful gene knock-in with DNA fragments larger than 4 kb. Here, we describe the targeted insertion of large DNA fragments (7.4 and 5.8 kb) into the genomes of mouse embryonic stem (ES) cells and zygotes, respectively, using the CRISPR/HDR technique without NHEJ inhibitors. Our data show that CRISPR/HDR without NHEJ inhibitors can result in highly efficient gene knock-in, equivalent to CRISPR/HDR with NHEJ inhibitors. Although NHEJ is the dominant repair pathway associated with CRISPR-mediated double-strand breaks (DSBs), and biallelic gene knock-ins are common, NHEJ and biallelic gene knock-ins were not detected. Our results demonstrate that efficient targeted insertion of large DNA fragments without NHEJ inhibitors is possible, a result that should stimulate interest in understanding the mechanisms of high efficiency CRISPR targeting in general.