Category: Statistics

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1098-1103. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.025.

ABSTRACT

OBJECTIVE: To retrospectively analyze the genetic differences of thalassemia gene mutations among ethnic groups in Hechi, Guangxi.

METHODS: A total of 15 595 whole blood samples of residents of Hechi from January 1, 2020 to June 30, 2023 were screened for thalassemia, and the Gap-PCR method and RDB-PCR method were used to perform genetic testing on the positive samples. Gene sequencing was performed on the samples with positive screening results but negative genotyping results.

RESULTS: Among the 15 595 samples, 10 501 cases were screened positively, and 8 506 cases were thalassemia gene carriers among the positive samples, with a positive coincidence rate of 81.00%. Among them, there were 5 374 cases of α-thalassemia, 2 531 cases of β-thalassemia, and 601 cases of α+β compound thalassemia. A total of 13 mutant types were detected in α-thalassemia, including —^SEA (48.57%), –α ^3.7 (31.31%), α ^CS (8.57%) and –α ^4.2 (8.07%). A total of 17 mutant types were detected in β-thalassemia, mainly CD17 (48.27%) and CD41-42 (41.24%). The thalassemia gene carriers were mainly from the Zhuang (6 106 cases), Han (969 cases), Yao (793 cases), Mulam (275 cases), and Maonan (228 cases) ethnic groups. The comparison of constituent ratios within the above five ethnic groups demonstrated that there were differences in the proportions of — ^SEA, –α ^3.7, α ^CS , and –α ^4.2 among the Zhuang, Han, and Yao ethnic groups (P < 0.005). The proportion of α ^CS in the Mulam ethnic group was not significantly different from –α ^3.7 and –α ^4.2. The proportions of — ^SEA, -α^3.7, and α ^CS in the Maonan ethnic group were not significantly different. There were no significant differences in the proportion of CD17 and CD41-42 among the Han, Yao, Mulam and Maonan ethnic groups. The proportion of —^SEA was the highest in the Mulam ethnic group (56.68%), which was statistically different from 35.92% in the Maonan ethnic group. The proportion of –α ^3.7 was the highest in the Zhuang ethnic group (33.25%), and the difference was statistically significant compared to the Mulam ethnic group which had the lowest proportion (18.72%). The proportion of α ^CS was the highest in the Maonan ethnic group (27.46%), and the differences were statistically significant compared with other ethnic groups. The proportions of CD17 in the Zhuang and Maonan ethnic groups (50.79%, 55.68%) were higher than those in the Han (39.12%), Yao (39.63%) and Mulam (30.00%), and the differences were statistically significant. There was no significant difference in the proportion of CD41-42 among the above five ethnic groups.

CONCLUSIONS: The mutation type and distribution differences of genes causing thalassemia among main ethnic groups in the minority inhabited areas of Hechi, Guangxi, show the characteristics of ethnic differentiation. The result is helpful to develop a special prevention and control plan for thalassemia in line with the population distribution characteristics, and provide reference for revealing the genetic background and geographical distribution of thalassemia in this area.

PMID:40936136 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.025

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1086-1093. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.023.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with hemophagocytic lymphohistiocytosis (HLH).

METHODS: Clinical data of 78 patients with HLH admitted to Gansu Provincial People’s Hospital from January 2014 to May 2023 were collected, and the correlation between relevant indicators and patient prognosis was analyzed.

RESULTS: Among the 78 HLH patients, there were 48 males and 30 females, with a median age of onset of 48 (1-84) years old; 26 patients were treated with chemotherapy, 44 patients were treated with glucocorticoids, immunoglobulin or cyclosporine, 5 patients received symptomatic treatment, 1 patient received plasma exchange, and 2 patients refused treatment. By the end of the follow-up, there were 39 survivors, 35 deaths, and 4 patients lost to follow-up. There was no significant correlation between sex, ferritin, triglycerides, hemophagocytosis, bone marrow cellularity, Epstein-Barr virus (EBV) infection, SUV value of PET-CT, alanine aminotransferase (ALT), interleukin-6 (IL-6), platelet-to-lymphocyte ratio (PLR) and overall survival (OS) of the patients (P >0.05). Patients with age≥60 years, neutrophil-to-lymphocyte ratio (NLR) >0.59, red cell distribution width-to-platelet ratio (RPR) >0.30, lymphocyte-to-monocyte ratio (LMR)≤2.74, red blood cell distribution width (RDW)>16.45%, tumor-associated HLH, aspartate aminotransferase (AST)≥148 U/L, procalcitonin (PCT)≥0.66 ng/ml, neutrophils (NEU) <2×10⁹/L, fibrinogen (FIB)<1.85 g/L, lactate dehydrogenase (LDH)≥1 740 U/L, hemoglobin (Hb)<85 g/L, platelet (PLT)<57×10⁹/L had significantly shorter OS, with statistical significance (P < 0.05). Multivariate analysis showed that LMR≤2.74, RDW>16.45%, LDH≥1 740 U/L, and NEU<2×10⁹/L were independent risk factors affecting OS in HLH patients (P < 0.05).

CONCLUSION: Some blood-based inflammatory markers are significantly associated with OS in patients with HLH. NLR, RPR, LMR, RDW and PCT can be used to assess the prognosis of HLH patients, and RDW and LMR are independent factors affecting OS of HLH patients, which provide greater predictive value for prognosis. Hypercellular bone marrow in HLH patients may indicate a poor prognosis.

PMID:40936134 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.023

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1069-1078. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.021.

ABSTRACT

OBJECTIVE: To construct the inflammation score (IS) and nutrition-immunity score (NIS) for patients with multiple myeloma (MM), and to verify their prognostic stratification effects and significance.

METHODS: The clinical data of 129 newly diagnosed MM patients admitted to our hospital from August 2011 to September 2022 were retrospectively analyzed. Univariate and multivariate Cox regression analysis of overall survival (OS) were comducted on clinical parameters, including inflammatory indicators such as red blood cell volume distribution width (RDW) and platelet count (PLT), nutritional-immune indicators such as albumin (ALB), absolute lymphocyte count (ALC), and suppressed immunoglobulin count (S-Ig count). To construct IS and NIS for prognosis, X-tile software and multivariate Cox regression analysis were used to verify the prognostic stratification role and significance of IS and NIS. The time-dependent receiver operating characteristic (ROC) curve, C-index curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical net benefit of IS and NIS in predicting overall survival(OS), and compared to the international staging system (ISS).

RESULTS: IS was constructed based on the scores of RDW and PLT, and NIS was constructed based on the scores of ALB, ALC, and S-Ig count. According to X-tile analysis and multivariate Cox regression analysis, IS and NIS can divide the patients into three risk strata respectively: low, medium and high IS and NIS groups. The differences in OS and hazard ratio (HR) between the low, medium, and high strata were statistically significant (P < 0.05). IS and NIS are both independent prognostic predictors for MM. The area under the ROC curve (AUC) and C index of IS and NIS for predicting 1- to 7-year OS were greater than those of ISS, and both were greater than 0.7. The prediction results of IS and NIS for 1-, 3-, and 5-year OS rates were well consistent with the actual observed results. The DCA curves of IS and NIS for predicting 1-, 3-, and 5-year OS were higher than that of ISS in a wide range of threshold probability intervals.

CONCLUSION: IS and NIS have independent predictive significance for OS in MM patients. Their predictive discrimination, accuracy, and clinical net benefit are higher and better than ISS, and they may have potential application value in MM prognosis.

PMID:40936132 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.021

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1036-1041. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.015.

ABSTRACT

OBJECTIVE: To investigate the relationship between Ig class switch recombination (CSR) and mismatch repair (MMR) protein, microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

METHODS: Forty cases of MALT lymphoma archived in the Department of Pathology, Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences were selected as the observation group, and twenty cases of benign lymphoid tissue hyperplasia were as the control group. The expressions of IgG, IgM, IgD, and IgA in both groups were detected by immunohistochemical double staining, and MMR proteins including MLH1, MSH2, MSH6, and PMS2 in both groups were detected by immunohistochemistry. Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group.

RESULTS: In the observation group, the proportions of single Ig heavy chain expression (modeⅠ), negative expression (modeⅡ), and multiple expression (mode Ⅲ) were 65% (26/40), 27.5% (11/40), and 7.5% (3/40), respectively, while in the control group were 0 (0/20), 5% (1/20), and 95% (19/20). The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5%, which was significantly higher than 5% in the control group (P < 0.01). In the observation group, partial deletion of MMR protein was observed in 3 cases (7.5%), including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion. In the control group, there was 1 case (5%) with PMS2 deletion. There was no significant difference in the deletion rate of MMR protein between the two groups ( P >0.05). A total of 5 cases of microsatellite instability (MSI) were detected in the observation group, including 1 case of low-frequency MSI (MSI-L), 4 cases of high-frequency MSI (MSI-H), and 2 cases of MSI-H with MSH6 deletion. When the loss expression of MSI-H or MMR protein was counted as a positive result, the MSI-H rate detected by PCR capillary electrophoresis was 10% (4/40), which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry (7.5%, 3/40), but there was no statistically significant difference between the two groups (P >0.05). The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ, mode Ⅱ, and mode Ⅲ groups were 0 (0/26), 18.2% (2/11), and 33.3% (1/3), respectively. There was a statistically significant difference in the constituent ratios among the three groups (P < 0.05). The MMR protein deletion rates among the MSS, MSI-L, and MSI-H groups were 2.9% (1/35), 0 (0/1), and 50% (2/4), respectively. There was a statistically significant difference in the constituent ratios among the three groups (P < 0.05). MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI ( r =0.41, P < 0.05; r =0.48, P < 0.05), but Ig heavy chain expression pattern was not correlated with MSI ( r =0.02, P >0.05).

CONCLUSION: Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma. Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma, which may be of certain value for the study of its occurrence, development and clinical treatment.

PMID:40936126 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.015

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):966-971. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.006.

ABSTRACT

OBJECTIVE: To analyze clinical characteristics and prognosis of B-cell acute lymphoblastic leukemia (B-ALL) patients with IKZF1 deletion.

METHODS: 72 patients with B-ALL admitted to our hospital from April 2020 to January 2023 were selected, IKZF1 deletion were detected, and clinical characteristics and prognosis were analyzed.

RESULTS: Among the 72 patients, a total of 32 patients (44.4%) were identified with IKZF1 deletions (IKZF1 ⁺ ). There was no statistically significant difference in basic clinical data between patients with normal IKZF1 (IKZF1 ^–) and those with IKZF1 ⁺ (P >0.05). The proportion of patients with IKZF1 ⁺ in Ph⁺ group was significantly higher than that in Ph^– group (P < 0.05). The main types of IKZF1 ⁺ were exon 1-8 deletion (34.4%) and exon 4-7 deletion (31.2%). The median OS and PFS of IKZF1 ^– patients were significantly longer than those of IKZF1 ⁺ patients (OS: 26.0 months vs 16.0 months, χ ²=23.094, P < 0.05; PFS: 26.0 months vs 16.0 months, χ ²=11.150, P < 0.05). Among IKZF1 ⁺ patients, the median OS of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was significantly longer than that of patients who did not receive allo-HSCT (no reached vs 15.0 months, χ ²=5.685, P < 0.05).

CONCLUSION: IKZF1 deletion is a risk factor affecting the prognosis of B-ALL patients.

PMID:40936117 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.006

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):931-938. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.001.

ABSTRACT

OBJECTIVE: To explore the effects of hydroxychloroquine (HCQ) on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia (AML) and its molecular mechanism.

METHODS: Bone marrow or peripheral blood samples of 36 AML patients with severe infection (AML-SI) and 29 AML patients without infection (AML-NI) after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023. In addition, the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group. The mRNA expressions of CXCL12, CXCR4 and CXCR7 were detected by RT-qPCR technology, and the levels of IL-6, IL-8 and TNF-α were detected by ELISA. Leukemia-derived THP-1 cells were selected and constructed as AML disease model. At the same time, bone marrow mesenchymal stem cells (BM-MSCs) from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group. THP-1 cells were treated with different concentration gradients of HCQ. The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry. ELISA was used to detect the changes of IL-6, IL-8 and TNF-α levels in the supernatant of the cell co-culture system, RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis, and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins.

RESULTS: CXCL12, CXCR4, CXCR7, as well as IL-6, IL-8, and TNF-α were all abnormally increased in AML patients, and the increases were more significant in AML-SI patients (P <0.01). Furthermore, there were statistically significant differences between AML-NI patients and AML-SI patients (all P <0.05). HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells, but the low concentration of HCQ had no significant effect on the killing of THP-1 cells. When THP-1 cells were co-cultured with BM-MSCs of AML patients, the levels of IL-6, IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group (all P <0.01). After HCQ intervention, the levels of IL-6, IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention (all P <0.01). Similarly, those of Co-culture group were also significantly decreased (all P <0.001). However, the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ. HCQ could up-regulate the expression of pro-apoptotic protein Bax, down-regulate the expression of anti-apoptotic protein Bcl-2, as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κB pathway, then induce the programmed death of THP-1 cells after intervention.

CONCLUSION: The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients. HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells. The mechanisms may be related to regulating the expression of Bcl-2 family proteins, hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κB signaling pathway.

PMID:40936112 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.001

Orthop Surg. 2025 Sep 11. doi: 10.1111/os.70140. Online ahead of print.

ABSTRACT

OBJECTIVE: This systematic review and network meta-analysis was performed to explore the optimal dose, efficacy, and safety of tranexamic acid (TXA) treatments versus placebo for high tibial osteotomy (HTO) patients.

METHODS: PubMed, Embase, Cochrane Library, Wanfang database, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for the randomized controlled trials (RCTs) meeting prespecified inclusion criteria up to March 2024. Interventions included TXA and placebo treatments. The outcomes included total blood loss, drainage, hemoglobin drop, the occurrence of deep venous thrombosis (DVT) and hematoma. Traditional meta-analysis and network meta-analysis were performed by Stata and R software, respectively.

RESULTS: Traditional meta-analysis revealed that TXA was associated with a decrease in the total blood loss, drainage volume, and hemoglobin drop (p < 0.05). There was no significant difference between TXA and placebo in terms of the occurrence of DVT and hematoma (p > 0.05). Compared with placebo, intravenous (iv) 10 mg/kg, iv 10 mg/kg (3 doses), iv 2 g, iv 2 g (2 doses), iv 2 g + topical (top) 3 g, iv 50 mg/kg, and top 10 mg/kg decreased the total blood loss with statistical significance (p < 0.05). Compared with placebo, iv 10 mg/kg (WMD = -379.91, 95% CI: -378.92, -81.22) decreased the drainage volume with statistical significance. Compared with placebo, iv 10 mg/kg (3 doses), iv 1 g, iv 1 g + top 2 g, iv 2 g + top 1 g, and iv 50 mg/kg decreased the hemoglobin drop with statistical significance. No statistically significant difference was found when the two interventions were compared against each other for the occurrence of DVT and hematoma (p > 0.05). The SUCRA shows that iv 10 mg/kg ranked first for reducing total blood loss (SUCRA, 90.7%) and drainage volume (SUCRA, 94.3%). The SUCRA shows that iv 1 g + top 2 g ranked first (SUCRA, 93.7%) for reducing hemoglobin drop.

CONCLUSION: Administration with TXA was associated with a decrease in blood loss in HTO patients. The optimal dose of TXA for reducing blood loss was iv 10 mg/kg. As for reducing hemoglobin drop, iv 1 g + top 2 g ranked first. Administration of TXA was not associated with an increase in the occurrence of DVT and hematoma. However, most evidence was graded as low/very low confidence due to study limitations, imprecision, and heterogeneity. Therefore, these findings should be interpreted as preliminary signals rather than definitive conclusions. Further high-quality randomized trials are required to validate dose-dependent efficacy and long-term safety outcomes.

PMID:40936101 | DOI:10.1111/os.70140

BMC Glob Public Health. 2025 Sep 12;3(1):76. doi: 10.1186/s44263-025-00189-z.

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions (NPIs) in response to the COVID-19 pandemic necessitated a trade-off between the health impacts of viral spread and the social and economic costs of restrictions. Navigating this trade-off proved consequential, contentious, and challenging for decision-makers.

METHODS: We conduct a cost-effectiveness analysis of NPIs enacted at the state level in the United States (US) in 2020. We combine data on COVID-19 cases, deaths, policies, and the social, economic, and health consequences of infections and interventions within an epidemiological model. We estimate SARS-CoV-2 prevalence, transmission rates, effects of interventions, and costs associated to infections and NPIs in each US state. We use these estimates to quantitatively evaluate the efficacy and gross impacts of the policy schedules implemented during the pandemic. We also derive optimal cost-effective strategies that minimize aggregate costs to society.

RESULTS: We find that NPIs were effective in substantially reducing SARS-CoV-2 transmission, averting 860,000 (95% CI: 560,000-1,190,000) COVID-19 deaths in the US in 2020. Although school closures reduced transmission, their social impact in terms of student learning loss was too costly, depriving the nation of $2 trillion in 2020 US dollars (USD2020), conservatively, in future Gross Domestic Product (GDP). Moreover, this marginal trade-off between school closure and COVID-19 deaths was not inescapable: a combination of other measures would have been enough to maintain similar or lower mortality rates without incurring such profound learning loss. Optimal policies involve consistent implementation of mask mandates, public test availability, contact tracing, social distancing orders, and reactive workplace closures, with no closure of schools. Their use would have reduced the gross impact of the pandemic in the US in 2020 from $4.6 trillion to $1.9 trillion and, with high probability, saved over 100,000 lives.

CONCLUSIONS: US COVID-19 school closure was not cost-effective, but other measures were. While our study focuses on COVID-19 in the US prior to vaccines, our methodological contributions and findings about the cost-effectiveness and optimal structure of NPI policies have implications for the response to future epidemics and in other countries. Our results also highlight the need to address the substantial global learning deficit incurred during the pandemic.

PMID:40936091 | DOI:10.1186/s44263-025-00189-z

BMC Plant Biol. 2025 Sep 12;25(1):1201. doi: 10.1186/s12870-025-07214-1.

ABSTRACT

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) can stimulate root development in plants and enhance their ability to adapt to stress conditions. This study investigated the effects of arbuscular mycorrhizal fungi (AMF) inoculation on the growth, hormone dynamics, and phosphorus (P) metabolism of two wheat cultivars with differing phosphorus utilization efficiencies under both normal and low phosphorus concentration conditions. The research focused on the symbiotic interaction between AMF and these wheat varieties to elucidate their responses to varying phosphorus availability.

RESULT: The experiment showed that phosphorus inefficient wheat SW14 inoculated with AMF for 30 days under low phosphorus stress showed significant enhancement in plant height, biomass, leaf width, stem thickness, root surface area, and vegetative phosphorus content, while total root length and primary root length were reduced, This change in root length was attributed to the fact that the root system undergoes elongation and growth to adapt to the adversity under low phosphorus stress in crops, and inoculation with AMF effectively alleviated the extent of this low phosphorus stress. while IAA, SL, cellulose and lignin hormone levels and APC enzyme activities were significantly elevated, and stem structure was significantly optimized; whereas, the phosphorus-efficient variety, SW2, did not show significant improvement due to its own unique tolerance to low phosphorus stress (Table 2). Transcriptomic profiling identified 2,500 differentially expressed genes (DEGs: 983↑/1,517↓), enriched in ABC transporters (ko02010), Plant hormone signal transduction (ko04075), and MAPK signaling pathway – plant (ko04016), Cutin, suberin and wax biosynthesis(ko00073). WGCNA further resolved that AMF responded to low phosphorus stress by up-regulating the expression of cellulose, lignin, APC synthesis, and IAA/SL-related genes in SW14, with the most relevant phenotypes shown to correlate to primary root length, total root length, root dry weight and stem diameter.

CONCLUSION: AMF inoculation significantly enhanced growth and dry matter accumulation in the low-phosphorus-use-efficiency wheat variety SW14 under phosphorus-deficient stress. This treatment concurrently stimulated IAA, SL, and APC activities, resulting in increased phosphorus uptake/accumulation, notable accumulation of cellulose and lignin, and consequently significantly improved stem strength. Although AMF inoculation improved growth in the high-phosphorus-use-efficiency wheat variety SW2, these enhancements failed to reach statistical significance.

PMID:40936089 | DOI:10.1186/s12870-025-07214-1

Epigenetics Chromatin. 2025 Sep 12;18(1):59. doi: 10.1186/s13072-025-00626-1.

ABSTRACT

DNA-methylation is a key epigenetic mark in chromatin that attenuates chromatin accessibility during transcription, implying a crucial role in gene regulation. Its symmetrical distribution and function is thought to be linked to the periodicity of the DNA helix and the positioning of DNA wrapped around the nucleosome. Epigenomic data suggest that DNA methyltransferases (DNMTs) can methylate DNA when wrapped around a histone octamer. Yet, how this is precisely linked to positioning and periodicity is yet to be elucidated. It has been hypothesized that the observed methylation patterns may be related to the changing accessibility of nucleosome-bound DNA to DNMTs. Here, incorporating NOMe-Seq data, which simultaneously measures nucleosome positioning and DNA methylation at CpG sites across the genome, the interaction of DNMT1 with nucleosomal DNA could be mechanistically modeled and compared to hypothesized dependencies. Furthermore, X-ray structures of DNMT1 were superimposed onto those of nucleosome core complexes at base resolution to determine which histone-bound DNA positions would be sterically accessible or inaccessible to DNMTs. Statistical comparison with experimental NOMe-Seq data revealed that structurally computed DNA accessibility scores can indeed explain DNA methylation patterns in actively transcribed regions with positioned high nucleosome density.

PMID:40936088 | DOI:10.1186/s13072-025-00626-1