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Aim: Public trust and confidence determine the acceptance of any population-based genome project. The Hong Kong Genome Institute (HKGI) was established in May 2020 by the Food and Health Bureau (Currently the Health Bureau) to spearhead the integration of genomic medicine into mainstream healthcare. One of HKGI’s goals is to enhance public genomic literacy and engagement by launching the Hong Kong Genome Project (HKGP).Methods: Three focus groups (undiagnosed and rare disease patients and their families, hereditary cancer patients and their families, and clinical geneticists and other medical subspecialists) involving 20 patients, family members, and healthcare professionals were completed in mid-2021 by an independent party. The aim was to harness insights into stakeholders’ views, concerns, and aspirations on issues related to genomic studies and the HKGP: (1) the decision to undergo genetic testing; (2) concerns; (3) campaign format; and (4) other strategic suggestions for the Pilot Phase. These issues are complex and multifactorial and have not been documented in Chinese populations. The qualitative approach facilitates such exploration.Results: Four themes emerged from the thematic analysis: (1) decisional considerations of undertaking genetic testing: perceived benefits and motivators; (2) concerns and worries: personal, familial, and societal concerns; (3) a quest for a patient-oriented, transparent, and decommercialized whole-genome sequencing campaign; and (4) communicating genomics efficaciously: the importance of informational support and literacy enhancement.Conclusion: Our results shaped the strategies for publicizing the Pilot Phase of HKGP and laid a patient-oriented foundation for HKGP’s Main Phase. LESS      Full article

Aim: Recent developments in single-cell RNA sequencing (scRNAseq) and analysis have revealed regulatory behaviors not previously described using bulk analysis. scRNAseq features resolution at the level of the individual cell and provides opportunities for identifying cell type-specific gene regulatory networks. The technology promises to discover biomarkers and targeted treatments with enhanced effectiveness and reduced side effects. Pathway reverse engineering and causal algorithms have been validated in bulk sequencing transcriptomic data successfully for gene regulatory network reconstruction. In the current study, we evaluated the performance of local causal discovery algorithms for de novo reconstruction of local gene regulatory networks tailored to scRNAseq count data.Method: We benchmarked the performance of the state-of-the-art local causal discovery algorithm generalized local learning with five conditional independent tests in controlled conditions (simulated count data) and real-world single-cell RNA sequencing datasets.Results: The simulation study showed that local causal discovery methods with appropriate conditional independence tests could result in excellent discovery performance (given a sufficient sample size). As expected, various conditional independence tests possess different power-sample characteristics. The discovery performance for all tested conditional independence tests on real-world data is relatively low, potentially due to imperfect standards or deviation of simulated data distribution from real-world data.Conclusion: Our findings provide insights and practical guidance for applying causal discovery methods to single-cell RNAseq data for gene regulatory network reconstruction. LESS      Full article

Interest in inherited cardiovascular conditions (ICCs) is fueled by resources devoted to its diagnosis, management, and research. The rapid advancement of DNA genomic sequencing deepens our understanding of ICCs. The ICC genomic landscape empowers the development of diagnostic guidelines and the discovery of potential therapeutic targets and promises novel therapeutics, especially in precision cardiology. Therefore, it is essential for healthcare institutes and systems to develop contextual frameworks based on current guidelines to provide holistic care for patients with ICCs. The clinical frameworks and considerations described in this review provide an overview of the operations of an ICC clinic, including wet and dry lab conditions, work performed by a healthcare professional, and the variety of cases, ranging from cardiomyopathies to arrythmias to aortopathies. Insights from our experience in an ICC clinic in Singapore add to the discussion of the challenges and benefits for patients and clinicians who serve them. LESS      Full article

Public and patient involvement (PPI) - the collaboration in research with members of the public and patients with relevant experience - is becoming well established in health service research in the UK. It is supported by funders and academic institutions. Published principles and guidelines for researchers, developed through consultation and consensus building, are available. Meanwhile, as genome sequencing is adopted into routine health care, translational genomics research and research to evaluate new genomic services are growing. Given the ethical and social implications of offering genome sequencing within a national health service, it is important that researchers give full consideration to planning and implementing meaningful PPI. Here we present five case studies of PPI in a variety of clinical genomic studies, including commentary on positive impacts and suggestions for improvements. We call for funders and academic institutions to continue and increase their efforts to enable and promote PPI across genomic and other health service research. LESS      Full article

Aim: Obesity and obesogenic diets might partly accelerate cancer development through epigenetic mechanisms. To determine these early effects, we investigated the impact of three days of a high-fat diet on epigenomic and transcriptomic changes in Apc^Min/+ murine intestinal epithelia.Method: ChIP-Seq and RNA-Seq were performed on small intestinal epithelia of WT and Apc^Min/+ male mice fed high-fat diet (HFD) or low-fat diet (LFD) for three days to identify genomic regions associated with differential H3K27ac levels as a marker of variant enhancer loci (VELs) as well as differentially expressed genes (DEGs).Results: Regarding epigenetic and transcriptomic changes, diet type (LFD vs. HFD) showed a significant impact, and genotype (WT vs. Apc^Min/+) showed a small impact. Compared to LFD, HFD resulted in 1306 gained VELs, 230 lost VELs, 133 upregulated genes, and 127 downregulated genes in WT mice, with 1056 gained VELs, 371 lost VELs, 222 upregulated genes, and 182 downregulated genes in Apc^Min/+ mice. Compared to the WT genotype, theApc^Min/+ genotype resulted in zero changed VELs for either diet type group, 21 DEGs for LFD, and 48 DEGs for HFD. Most gained VELs, and upregulated genes were associated with lipid metabolic processes. Gained VELs were also associated with Wnt signaling. Downregulated genes were associated with antigen presentation and processing.Conclusion: Three days of HFD-induced epigenomic and transcriptomic changes involving metabolic and immunologic pathways that may promote tumor growth in the genetically predisposed murine intestine without affecting key cancer signaling pathways. LESS      Full article