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1.
BMC Bioinformatics ; 25(1): 140, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38561679

Drug combination therapy is generally more effective than monotherapy in the field of cancer treatment. However, screening for effective synergistic combinations from a wide range of drug combinations is particularly important given the increase in the number of available drug classes and potential drug-drug interactions. Existing methods for predicting the synergistic effects of drug combinations primarily focus on extracting structural features of drug molecules and cell lines, but neglect the interaction mechanisms between cell lines and drug combinations. Consequently, there is a deficiency in comprehensive understanding of the synergistic effects of drug combinations. To address this issue, we propose a drug combination synergy prediction model based on multi-source feature interaction learning, named MFSynDCP, aiming to predict the synergistic effects of anti-tumor drug combinations. This model includes a graph aggregation module with an adaptive attention mechanism for learning drug interactions and a multi-source feature interaction learning controller for managing information transfer between different data sources, accommodating both drug and cell line features. Comparative studies with benchmark datasets demonstrate MFSynDCP's superiority over existing methods. Additionally, its adaptive attention mechanism graph aggregation module identifies drug chemical substructures crucial to the synergy mechanism. Overall, MFSynDCP is a robust tool for predicting synergistic drug combinations. The source code is available from GitHub at https://github.com/kkioplkg/MFSynDCP .


Benchmarking , Simulation Training , Drug Combinations , Drug Therapy, Combination , Cell Line
2.
Phys Med Biol ; 69(8)2024 Apr 09.
Article En | MEDLINE | ID: mdl-38417177

Objective. Honeycomb lung is a rare but severe disease characterized by honeycomb-like imaging features and distinct radiological characteristics. Therefore, this study aims to develop a deep-learning model capable of segmenting honeycomb lung lesions from Computed Tomography (CT) scans to address the efficacy issue of honeycomb lung segmentation.Methods. This study proposes a sparse mapping-based graph representation segmentation network (SM-GRSNet). SM-GRSNet integrates an attention affinity mechanism to effectively filter redundant features at a coarse-grained region level. The attention encoder generated by this mechanism specifically focuses on the lesion area. Additionally, we introduce a graph representation module based on sparse links in SM-GRSNet. Subsequently, graph representation operations are performed on the sparse graph, yielding detailed lesion segmentation results. Finally, we construct a pyramid-structured cascaded decoder in SM-GRSNet, which combines features from the sparse link-based graph representation modules and attention encoders to generate the final segmentation mask.Results. Experimental results demonstrate that the proposed SM-GRSNet achieves state-of-the-art performance on a dataset comprising 7170 honeycomb lung CT images. Our model attains the highest IOU (87.62%), Dice(93.41%). Furthermore, our model also achieves the lowest HD95 (6.95) and ASD (2.47).Significance.The SM-GRSNet method proposed in this paper can be used for automatic segmentation of honeycomb lung CT images, which enhances the segmentation performance of Honeycomb lung lesions under small sample datasets. It will help doctors with early screening, accurate diagnosis, and customized treatment. This method maintains a high correlation and consistency between the automatic segmentation results and the expert manual segmentation results. Accurate automatic segmentation of the honeycomb lung lesion area is clinically important.


Pyramidal Tracts , Radiology , Tomography, X-Ray Computed , Lung/diagnostic imaging , Image Processing, Computer-Assisted
3.
FEBS Lett ; 592(24): 4039-4050, 2018 12.
Article En | MEDLINE | ID: mdl-30372528

Toxin-antitoxin (TA) systems are regarded as genetic modules that facilitate bacterial survival under stress conditions. In this study, a novel TA system in Mycobacterium tuberculosis H37Rv chromosome was identified, termed as mt-PemIK, which consists of antitoxin mt-PemI and toxin mt-PemK (Rv3098A). Induction of mt-PemK leads to growth arrest in Mycobacterium smegmatis, while the toxic effect of mt-PemK is eliminated by co-expression of mt-PemI. mt-PemK is characterized as an endoribonuclease whose activity is pH-dependent. mt-PemK, as well as some other M. tuberculosis toxin/antitoxin proteins, can be modified by pupylation, suggesting that the Pup-proteasome system is involved in the regulation of TA systems. These results are helpful to understand the mechanisms of M. tuberculosis growth regulation under stress conditions.


Bacterial Proteins/genetics , Bacterial Toxins/genetics , Mycobacterium tuberculosis/genetics , Toxin-Antitoxin Systems/genetics , Amino Acid Sequence , Bacterial Proteins/metabolism , Bacterial Toxins/metabolism , Endoribonucleases/genetics , Endoribonucleases/metabolism , Gene Expression Profiling , Gene Expression Regulation, Bacterial , Gene Ontology , Hydrogen-Ion Concentration , Mycobacterium tuberculosis/metabolism , Sequence Homology, Amino Acid
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