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FAN, P.

Publications and source records attributed to FAN, P..

2 recordsLinked to original sources

Age Prediction based on Blood DNA Methylation

ObjectiveIn the judicial field, traditional DNA methylation age prediction models have low accuracy and poor stability. Additionally, the use of linear regression models for detection is inefficient and costly. This study aims to utilize the prediction principles of the Support Vector Regression (SVR) model, based on preliminary laboratory data from blood DNA methylation detection using the Illumina 850K chip. By selecting low-dimensional and highly linear loci, we aim to establish a highly stable and accurate blood DNA methylation age prediction model. MethodsThis research is based on Illumina 850K chip technology. We conducted a literature review to select CpG sites and related primers, then employed SVR for model construction and age prediction. The model was built on the Matlab2022a platform. Standard parameters were selected, and optimal values for C and g were determined using grid search and cross-validation methods. During data processing, numerical values were normalized before calculation and de-normalized to obtain the predicted values. ResultsThe constructed model achieved an R2 of 0.91563 and a Mean Absolute Error (MAE) of 2.77 years. This indicates that the prediction accuracy for blood samples reached 91.56%, with an error of 2.77 years. Moreover, the accuracy of the models predictions decreases with increasing age.

genetics↗

Catalytic-independent functions of INTAC in conferring sensitivity to BET inhibition

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs with poorly understood mechanisms. Using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary module of the INTAC complex, a global regulator of polymerase pause-release dynamics. This process bypasses a requirement for INTACs catalytic activities and instead leverages direct engagement of the auxiliary module with the RACK7/ZMYND8-KDM5C complex to remove histone H3K4 methylation. Targeted degradation of the COMPASS subunit WDR5 to attenuate H3K4 methylation restores sensitivity to BET inhibitors, highlighting how simultaneously targeting coordinated chromatin and transcription regulators can circumvent drug-resistant tumors.

molecular biology↗