Hi-Tag: a simple and efficient method for identifying protein-mediated long-range chromatin interactions with low cell numbers.

Protein-mediated chromatin interactions can be revealed by coupling proximity-based ligation with chromatin immunoprecipitation. However, these techniques require complex experimental procedures and millions of cells per experiment, which limits their widespread application in life science research. Here, we develop a novel method, Hi-Tag, that identifies high-resolution, long-range chromatin interactions through transposase tagmentation and chromatin proximity ligation (with a phosphorothioate-modified linker). Hi-Tag can be implemented using as few as 100,000 cells, involving simple experimental procedures that can be completed within 1.5 days. Meanwhile, Hi-Tag is capable of using its own data to identify the binding sites of specific proteins, based on which, it can acquire accurate interaction information. Our results suggest that Hi-Tag has great potential for advancing chromatin interaction studies, particularly in the context of limited cell availability.

Enhancer-promoter interaction maps provide insights into skeletal muscle-related traits in pig genome.

BACKGROUND: Gene expression programs are intimately linked to the interplay of active cis regulatory elements mediated by chromatin contacts and associated RNAs. Genome-wide association studies (GWAS) have identified many variants in these regulatory elements that can contribute to phenotypic diversity. However, the functional interpretation of these variants remains nontrivial due to the lack of chromatin contact information or limited contact resolution. Furthermore, the distribution and role of chromatin-associated RNAs in gene expression and chromatin conformation remain poorly understood. To address this, we first present a comprehensive interaction map of nuclear dynamics of 3D chromatin-chromatin interactions (H3K27ac BL-HiChIP) and RNA-chromatin interactions (GRID-seq) to reveal genomic variants that contribute to complex skeletal muscle traits. RESULTS: In a genome-wide scan, we provide systematic fine mapping and gene prioritization from GWAS leading signals that underlie phenotypic variability of growth rate, meat quality, and carcass performance. A set of candidate functional variants and 54 target genes previously not detected were identified, with 71% of these candidate functional variants choosing to skip over their nearest gene to regulate the target gene in a long-range manner. The effects of three functional variants regulating KLF6 (related to days to 100 kg), MXRA8 (related to lean meat percentage), and TAF11 (related to loin muscle depth) were observed in two pig populations. Moreover, we find that this multi-omics interaction map consists of functional communities that are enriched in specific biological functions, and GWAS target genes can serve as core genes for exploring peripheral trait-relevant genes. CONCLUSIONS: Our results provide a valuable resource of candidate functional variants for complex skeletal muscle-related traits and establish an integrated approach to complement existing 3D genomics by exploiting RNA-chromatin and chromatin-chromatin interactions for future association studies.

Pharmacist-Led Management Improves Treatment Adherence and Quality of Life in Opioid-Tolerant Patients With Cancer Pain: A Randomized Controlled Trial.

INTRODUCTION: Opioid-tolerant patients are more likely to deviate from recommended treatments and to experience inadequate analgesia than opioid-naive ones. The aim of this study was to examine whether pharmacist-led management could help improve treatment adherence and quality of life. METHODS: Eligible patients were randomized in a 1:1 ratio to control group and intervention group. The control group received routine education and support, while the intervention group received additional individualized pharmacist-led care. The primary endpoint was treatment adherence in the per-protocol analysis, as evaluated by blinded assessors. An interim analysis was planned when 30% patients completed the study. Alpha was divided into the interim analysis (0.015) and the final analysis (0.035). RESULTS: In the interim analysis (97 and 87 patients in the control and intervention groups, respectively), the primary endpoint was met. Pharmacist-led intervention significantly increased treatment adherence (93.3 vs. 79.8%; OR: 2.25; 95% CI 1.02, 4.94; P = 0.013), quality of life (0.81 ± 0.17 vs. 0.72 ± 0.25; P = 0.008), and reporting of adverse events (82.7 vs. 61.9%; OR: 1.88; 95% CI 1.16, 3.07; P = 0.004). The two groups did not differ in pain control rate (66.7 vs. 57.1%; OR: 1.25; 95% CI 0.87, 1.78; P = 0.218), breakthrough pain-free rate (66.7 vs. 61.9%; OR: 1.12; 95% CI 0.78, 1.59; P = 0.532) and pain score (1.97 ± 1.04 vs. 2.15 ± 1.24; P = 0.522). CONCLUSIONS: Pharmacist-led management improved treatment adherence, quality of life, and the reporting of adverse events in opioid-tolerant patients with cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03455023.