Genomes in 3D are folded into organizational units that can influence critical biological functions. In particular, the organization of chromatin into A and B compartments segregates its active regions from the inactive regions. Compartments, evident in Hi-C contact matrices, have been used to describe cell-type specific changes in A/B organization. However, obtaining Hi-C data for all cell and tissue types of interest is prohibitively expensive, which has limited the widespread consideration of compartment status. We present a prediction tool called \textbf{Co}mpartment prediction using \textbf{R}ecurrent \textbf{N}eural \textbf{N}etwork (CoRNN) that models the relationship between the compartmental organization of the genome and histone modification enrichment. Our model predicts A/B compartments, in a cross-cell type setting, with an average area under the ROC score of 90.9$\%$. Our cell type specific compartment predictions show high overlap with known functional elements. We investigate our predictions by systematically removing combinations of histone marks and find that H3K27ac and H3K36me3 are the most predictive marks. We then perform a detailed investigation of loci where compartment status cannot be accurately predicted from these marks.These regions represent chromatin with ambiguous compartmental status, likely due to variations in status within the population of cells. As such these ambiguous loci also show highly variable compartmental status between biological replicates in the same GM12878 cell type. Our software and trained model are publicly available at \url{https://github.com/rsinghlab/CoRNN}.
Background: Adolescents and young adults (AYAs) with life-threatening illnesses need support to discuss and voice their end-of-life choices. Voicing My CHOiCES (VMC) is a research-informed American advanced care planning guide designed to help facilitate these difficult discussions. This multi-perspective study aimed to evaluate its appropriateness, acceptability, and clinical considerations for Australian AYAs with cancer. Procedure: Forty-three participants including AYAs who were either undergoing or recently completed cancer treatment, their parents, and multidisciplinary health professionals assessed the acceptability of each VMC section quantitatively (appropriateness—yes/no, helpfulness and whether content caused stress—1 = not at all, to 5 = very) and qualitatively (sources of stress). AYAs also assessed the benefit and burden of completing several sections of the document, to inform clinical considerations. We conducted a mixed-methods analysis to obtain descriptive statistics and to identify prominent themes. Results: In terms of acceptability, almost all participants (96%) rated VMC as appropriate overall. Perceived helpfulness to their situation (to themselves/their child/their patients), to others, and stressfulness were rated, on average, as 4.1, 4.0, and 2.7/5, respectively. Stress was attributed to individual and personal factors, as well as interpersonal worries. All sections were considered more beneficial than burdensome, except for the Spiritual Thoughts section (Section 6). Conclusions: While VMC is an acceptable advance care planning guide for AYAs with cancer, changes to the guide were suggested for the Australian context. Health professionals implementing VMC will need to address and mitigate anticipated sources of stress identified here. Future research evaluating the impact of a new culturally adapted Australian VMC guide is an important next step. Finally, the clinical implications of the present study are suggested.
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