UroMark-a urinary biomarker assay for the detection of bladder cancer.

BACKGROUND: Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity. RESULTS: We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort (n = 274, non-cancer (n = 167) and bladder cancer (n = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine. CONCLUSIONS: Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine

NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression

The NURD and Polycomb complexes PRC1 and PRC2 have been implicated in stem cell differentiation although their molecular roles are unclear. This study identifies a common set of genes that are sequentially regulated by these complexes, the NURD complex deacetylates H3K27 as a prerequisite for subsequent methylation by PRC2

Formation of a type 1 diabetes young adult patient and public involvement panel to develop a health behaviour change intervention: the D1 Now study

Plain English summary Many young adults with type 1 diabetes (T1D) find it hard to control their blood glucose levels. With lots of things going on in their lives, their diabetes is often not the most important thing to them. That means they do not always take care of their T1D, for example by going to clinic appointments. Young adults with T1D do not usually get the chance to make suggestions on how to improve diabetes services. Being involved could help young adults to shape the diabetes care services that support them. Since 2014 a diabetes research team based in Galway has been looking at ways to improve how diabetes services are delivered to young adults. Eight young adults (aged 18–25 years) with T1D called the Young Adult Panel (YAP) are members of this team and have helped design the “D1 Now” intervention which aims to improve diabetes services. The YAP came up with questions to ask other young adults with T1D, their families and friends and healthcare providers about their experiences of healthcare services and how these could be improved. The YAP also shared messages from the research at national conferences and on local radio. They helped with writing sections of a grant application to take this research work forward. Our experience has shown the importance of involving young adults with T1D in helping to design research focusing on ways to improve their diabetes service that will help them and other young adults to live with diabetes in the future. Abstract Background Research indicates that young adults (18–25 year olds) with type 1 diabetes (T1D) often disengage from health services and their general diabetes management. Involving young adults with T1D in co-designing research to develop a behaviour change intervention to improve engagement with health services could potentially improve overall self management and health. A local youth mental health organisation called Jigsaw, Galway developed a very successful model for involving users in service design and development. Based on this model, the aim was to form a Young Adult Panel (YAP) of 18–25 year olds with T1D and involve them in all aspects of a study to develop an intervention to improve health and wellbeing for young adults with T1D called D1 Now. Methods Recruitment of young adults was achieved through a multimedia campaign. A consultation event was organised, followed by interviews with interested young adults. A panel of 8 members was selected. Following initial training for YAP members in committee skills and an introduction to different research methods and terms, YAP members participated in different stages of the research process. They were represented on the research study steering group and attended research meetings. They developed research materials, reviewed and interpreted research findings and helped develop the online platform to enhance engagement between young adults and their diabetes healthcare providers. They contributed to an international consensus conference on health services delivery for young adults with T1D and wrote specific sections of a further grant application to test out the new intervention. Results As a direct result of the YAP, a meaningful dialogue has opened up between healthcare providers and young adults within the D1 Now research team. Their involvement has led to a better understanding of what needs to be achieved in order to improve health service delivery. They have been active members in co-designing a health behaviour change intervention to improve engagement between young adults with T1D and healthcare providers which will be evaluated in future research. Conclusion Through the formation of the YAP, we have demonstrated that involving young adults with T1D in healthcare research is feasible and productive

Additional file 4: Table S3. of UroMark—a urinary biomarker assay for the detection of bladder cancer

RainDance custom sequencing primers. (XLSX 8 kb

Additional file 2: Table S1. of UroMark—a urinary biomarker assay for the detection of bladder cancer

RainDance target primers. (XLSX 13 kb

Additional file 5: Figure S1. of UroMark—a urinary biomarker assay for the detection of bladder cancer

A) MDS plot of 150 UroMark loci panel, tumour = red, normal = blue, B) ROC for cross validation accuracy of 150 loci UroMark assay. Figure S2. A) MDS plot of 150 UroMark loci panel in 179 sample validation cohort, High grade = red, low grade = green, normal = blue, B) ROC for cross validation accuracy of 150 loci UroMark assay in the 179 sample validation cohort. Figure S3. A) Boxplots of methylation values for top 10 performing markers in the primary tissue training cohort. B) Boxplots of methylation values for top 10 performing markers in the in urine samples validation cohorts (normal – confirmed no tumour, tumour - histological confirmation of TCC). Figure S4. A) Boxplots of methylation values for top 10 performing markers in the primary tissue training cohort. B) Boxplots of methylation values for top 10 performing markers in the in urine samples validation cohorts (normal – confirmed no tumour, tumour histological confirmation of TCC). (PDF 164 kb