GWarrange: a pre- and post- genome-wide association studies pipeline for detecting phenotype-associated genome rearrangement events.

The use of k-mers to capture genetic variation in bacterial genome-wide association studies (bGWAS) has demonstrated its effectiveness in overcoming the plasticity of bacterial genomes by providing a comprehensive array of genetic variants in a genome set that is not confined to a single reference genome. However, little attempt has been made to interpret k-mers in the context of genome rearrangements, partly due to challenges in the exhaustive and high-throughput identification of genome structure and individual rearrangement events. Here, we present GWarrange, a pre- and post-bGWAS processing methodology that leverages the unique properties of k-mers to facilitate bGWAS for genome rearrangements. Repeat sequences are common instigators of genome rearrangements through intragenomic homologous recombination, and they are commonly found at rearrangement boundaries. Using whole-genome sequences, repeat sequences are replaced by short placeholder sequences, allowing the regions flanking repeats to be incorporated into relatively short k-mers. Then, locations of flanking regions in significant k-mers are mapped back to complete genome sequences to visualise genome rearrangements. Four case studies based on two bacterial species (Bordetella pertussis and Enterococcus faecium) and a simulated genome set are presented to demonstrate the ability to identify phenotype-associated rearrangements. GWarrange is available at https://github.com/DorothyTamYiLing/GWarrange.

Safe inhalation pipe provision (SIPP): protocol for a mixed-method evaluation of an intervention to improve health outcomes and service engagement among people who use crack cocaine in England.

BACKGROUND: Over 180,000 people use crack cocaine in England, yet provision of smoking equipment to support safer crack use is prohibited under UK law. Pipes used for crack cocaine smoking are often homemade and/or in short supply, leading to pipe sharing and injuries from use of unsafe materials. This increases risk of viral infection and respiratory harm among a marginalised underserved population. International evaluations suggest crack pipe supply leads to sustained reductions in pipe sharing and use of homemade equipment; increased health risk awareness; improved service access; reduction in injecting and crack-related health problems. In this paper, we introduce the protocol for the NIHR-funded SIPP (Safe inhalation pipe provision) project and discuss implications for impact. METHODS: The SIPP study will develop, implement and evaluate a crack smoking equipment and training intervention to be distributed through peer networks and specialist drug services in England. Study components comprise: (1) peer-network capacity building and co-production; (2) a pre- and post-intervention survey at intervention and non-equivalent control sites; (3) a mixed-method process evaluation; and (4) an economic evaluation. Participant eligibility criteria are use of crack within the past 28 days, with a survey sample of ~ 740 for each impact evaluation survey point and ~ 40 for qualitative process evaluation interviews. Our primary outcome measure is pipe sharing within the past 28 days, with secondary outcomes pertaining to use of homemade pipes, service engagement, injecting practice and acute health harms. ANTICIPATED IMPACT: SIPP aims to reduce crack use risk practices and associated health harms; including through increasing crack harm reduction awareness among service providers and peers. Implementation has only been possible with local police approvals. Our goal is to generate an evidence base to inform review of the legislation prohibiting crack pipe supply in the UK. This holds potential to transform harm reduction service provision and engagement nationally. CONCLUSION: People who smoke crack cocaine in England currently have little reason to engage with harm reduction and drug services. Little is known about this growing population. This study will provide insight into population characteristics, unmet need and the case for legislative reform. TRIAL REGISTRATION: ISRCTN12541454  https://doi.org/10.1186/ISRCTN12541454.