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OBJECTIVE: Identifying cancer driver genes, especially rare or patient-specific cancer driver genes, is a primary goal in cancer therapy. Although researchers have proposed some methods to tackle this problem, these methods mostly identify cancer driver genes at single gene level, overlooking the cooperative relationship among cancer driver genes. Identifying cooperating cancer driver genes in individual patients is pivotal for understanding cancer etiology and advancing the development of personalized therapies. METHODS: Here, we propose a novel Personalized Cooperating cancer Driver Genes (PCoDG) method by using hypergraph random walk to identify the cancer driver genes that cooperatively drive individual patient cancer progression. By leveraging the powerful ability of hypergraph in representing multi-way relationships, PCoDG first employs the personalized hypergraph to depict the complex interactions among mutated genes and differentially expressed genes of an individual patient. Then, a hypergraph random walk algorithm based on hyperedge similarity is utilized to calculate the importance scores of mutated genes, integrating these scores with signaling pathway data to identify the cooperating cancer driver genes in individual patients. RESULTS: The experimental results on three TCGA cancer datasets (i.e., BRCA, LUAD, and COADREAD) demonstrate the effectiveness of PCoDG in identifying personalized cooperating cancer driver genes. These genes identified by PCoDG not only offer valuable insights into patient stratification correlating with clinical outcomes, but also provide an useful reference resource for tailoring personalized treatments. CONCLUSION: We propose a novel method that can effectively identify cooperating cancer driver genes for individual patients, thereby deepening our understanding of the cooperative relationship among personalized cancer driver genes and advancing the development of precision oncology.
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OBJECTIVE: To investigate the influence of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with Coronary Heart Disease (CHD) and explore the possible causative role. METHODS: 45 Sprague Dawley® rats were randomized into model, control and experimental groups. A high-fat diet was adopted for generating a rat CHD model, and the experimental group was given a 4-week aerobic exercise intervention. ECG was utilized to evaluate the cardiac function of the rats; HE staining to evaluate the damage of myocardial tissue; TUNEL staining to evaluate cardiomyocyte apoptosis level; ELISA to assay the contents of inflammatory factors and glucolipid metabolism in cardiomyocytes; qPCR to assay IB- and NF-B mRNA expression; Western-blot to assay the apoptosis-related proteins and NF-B signaling pathway-related proteins expressions in myocardial tissue. RESULTS: In contrast to the model group, aerobic exercise strongly improved the rat's cardiac function and glucolipid metabolism (p < 0.01), enhanced IL-10 content, Bcl-2/Bax level as well as IB- protein and mRNA expression (p < 0.01), and reduced myocardial injury and cardiomyocyte apoptosis, the contents of IL-6, IL-1 and TNF-, Caspase 3 level, NF-B mRNA and protein expression and p-p38 and p-STAT3 expressions (p < 0.01). CONCLUSION: Aerobic exercise can not only effectively reduce myocardial injury, the release of inflammatory factors and NF-B expression in CHD rats, but also improve cardiac function and glucolipid metabolism. Its mechanism is likely to be related to the inhibition of the NF-B signaling pathway.
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Apoptosis , Enfermedad Coronaria , Modelos Animales de Enfermedad , FN-kappa B , Condicionamiento Físico Animal , Distribución Aleatoria , Ratas Sprague-Dawley , Animales , Condicionamiento Físico Animal/fisiología , FN-kappa B/metabolismo , Masculino , Enfermedad Coronaria/metabolismo , Apoptosis/fisiología , Miocitos Cardíacos/metabolismo , Miocardio/metabolismo , Metabolismo de los Lípidos/fisiología , Ratas , Western Blotting , Transducción de Señal/fisiología , Ensayo de Inmunoadsorción Enzimática , Dieta Alta en Grasa/efectos adversos , Etiquetado Corte-Fin in SituRESUMEN
As the most abundant mRNA modification, m6A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6Aexpress-enet) to predict which m6A site could potentially regulate its gene expression. Comprehensive evaluations on simulated datasets demonstrate that m6Aexpress-enet could achieve the top prediction performance. Applying m6Aexpress-enet on real MeRIP-seq data from human lymphoblastoid cell lines, we have uncovered the complex regulatory pattern of predicted m6A sites and their unique enrichment pathway of the constructed co-methylation modules. m6Aexpress-enet proves itself as a powerful tool to enable biologists to discover the mechanism of m6A regulatory gene expression. Furthermore, the source code and the step-by-step implementation of m6Aexpress-enet is freely accessed at https://github.com/tengzhangs/m6Aexpress-enet.
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Regulación de la Expresión Génica , ARN Mensajero , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación de la Expresión Génica/genética , Biología Computacional/métodos , Metilación , Programas Informáticos , Adenosina/metabolismo , Adenosina/genética , Adenosina/análogos & derivados , Análisis de RegresiónRESUMEN
TiNiCu0.025Sn0.99Sb0.01 is prepared using microwaves. However, an ultra-high electrical conductivity and electronic thermal conductivity are obtained by interstitial Cu and Sb doping, which could not effectively improve the ZT value. We introduce carbon dots (CDs) as a nano-second phase by ball milling to simultaneously optimize the thermoelectric properties. To our best knowledge, this is the first report on half-Heusler/CDs composites. Experimental results show that the introduction of nano-CDs optimizes the carrier concentration and mobility and dramatically improves the Seebeck coefficient through the energy filtering effect. The nano-CDs introduce more point defects, inhibit the grains growth, and form a specific carbon solid solution second phase in the matrix. The lattice thermal conductivity is reduced to the same level as TiNiSn at 1.96 W m-1 K-1 through the synergistic effect of point defects and phase and grain boundaries scattering, and the ZT value reaches a maximum of 0.63 at 873 K.
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Abstract Objective To investigate the influence of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with Coronary Heart Disease (CHD) and explore the possible causative role. Methods 45 Sprague Dawley® rats were randomized into model, control and experimental groups. A high-fat diet was adopted for generating a rat CHD model, and the experimental group was given a 4-week aerobic exercise intervention. ECG was utilized to evaluate the cardiac function of the rats; HE staining to evaluate the damage of myocardial tissue; TUNEL staining to evaluate cardiomyocyte apoptosis level; ELISA to assay the contents of inflammatory factors and glucolipid metabolism in cardiomyocytes; qPCR to assay IB- and NF-B mRNA expression; Western-blot to assay the apoptosis-related proteins and NF-B signaling pathway-related proteins expressions in myocardial tissue. Results In contrast to the model group, aerobic exercise strongly improved the rat's cardiac function and glucolipid metabolism (p < 0.01), enhanced IL-10 content, Bcl-2/Bax level as well as IB- protein and mRNA expression (p < 0.01), and reduced myocardial injury and cardiomyocyte apoptosis, the contents of IL-6, IL-1 and TNF-, Caspase 3 level, NF-B mRNA and protein expression and p-p38 and p-STAT3 expressions (p < 0.01). Conclusion Aerobic exercise can not only effectively reduce myocardial injury, the release of inflammatory factors and NF-B expression in CHD rats, but also improve cardiac function and glucolipid metabolism. Its mechanism is likely to be related to the inhibition of the NF-B signaling pathway.
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Alzheimer's disease (AD) is an irreversible central nervous degenerative disease, while mild cognitive impairment (MCI) is a precursor state of AD. Accurate early diagnosis of AD is conducive to the prevention and early intervention treatment of AD. Although some computational methods have been developed for AD diagnosis, most employ only neuroimaging, ignoring other data (e.g., genetic, clinical) that may have potential disease information. In addition, the results of some methods lack interpretability. In this work, we proposed a novel method (called DANMLP) of joining dual attention convolutional neural network (CNN) and multilayer perceptron (MLP) for computer-aided AD diagnosis by integrating multi-modality data of the structural magnetic resonance imaging (sMRI), clinical data (i.e., demographics, neuropsychology), and APOE genetic data. Our DANMLP consists of four primary components: (1) the Patch-CNN for extracting the image characteristics from each local patch, (2) the position self-attention block for capturing the dependencies between features within a patch, (3) the channel self-attention block for capturing dependencies of inter-patch features, (4) two MLP networks for extracting the clinical features and outputting the AD classification results, respectively. Compared with other state-of-the-art methods in the 5CV test, DANMLP achieves 93% and 82.4% classification accuracy for the AD vs. MCI and MCI vs. NC tasks on the ADNI database, which is 0.2%â¼15.2% and 3.4%â¼26.8% higher than that of other five methods, respectively. The individualized visualization of focal areas can also help clinicians in the early diagnosis of AD. These results indicate that DANMLP can be effectively used for diagnosing AD and MCI patients.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Imagen por Resonancia Magnética/métodos , Redes Neurales de la Computación , Neuroimagen/métodos , Diagnóstico por Computador , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/genéticaRESUMEN
Accurate segmentation of the hippocampus from the brain magnetic resonance images (MRIs) is a crucial task in the neuroimaging research, since its structural integrity is strongly related to several neurodegenerative disorders, such as Alzheimer's disease (AD). Automatic segmentation of the hippocampus structures is challenging due to the small volume, complex shape, low contrast and discontinuous boundaries of hippocampus. Although some methods have been developed for the hippocampus segmentation, most of them paid too much attention to the hippocampus shape and volume instead of considering the spatial information. Additionally, the extracted features are independent of each other, ignoring the correlation between the global and local information. In view of this, here we proposed a novel cross-layer dual Encoding-Shared Decoding network framework with Spatial self-Attention mechanism (called ESDSA) for hippocampus segmentation in human brains. Considering that the hippocampus is a relatively small part in MRI, we introduced the spatial self-attention mechanism in ESDSA to capture the spatial information of hippocampus for improving the segmentation accuracy. We also designed a cross-layer dual encoding-shared decoding network to effectively extract the global information of MRIs and the spatial information of hippocampus. The spatial features of hippocampus and the features extracted from the MRIs were combined to realize the hippocampus segmentation. Results on the baseline T1-weighted structural MRI data show that the performance of our ESDSA is superior to other state-of-the-art methods, and the dice similarity coefficient of ESDSA achieves 89.37%. In addition, the dice similarity coefficient of the Spatial Self-Attention mechanism (SSA) strategy and the dual Encoding-Shared Decoding (ESD) strategy is 9.47%, 5.35% higher than that of the baseline U-net, respectively, indicating that the strategies of SSA and ESD can effectively enhance the segmentation accuracy of human brain hippocampus.
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Enfermedad de Alzheimer , Hipocampo , Humanos , Hipocampo/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Encéfalo/diagnóstico por imagen , Neuroimagen , Salarios y Beneficios , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia MagnéticaRESUMEN
Identifying personalized cancer driver genes and further revealing their oncogenic mechanisms is critical for understanding the mechanisms of cell transformation and aiding clinical diagnosis. Almost all existing methods primarily focus on identifying driver genes at the cohort or individual level but fail to further uncover their underlying oncogenic mechanisms. To fill this gap, we present an interpretable framework, PhenoDriver, to identify personalized cancer driver genes, elucidate their roles in cancer development and uncover the association between driver genes and clinical phenotypic alterations. By analyzing 988 breast cancer patients, we demonstrate the outstanding performance of PhenoDriver in identifying breast cancer driver genes at the cohort level compared to other state-of-the-art methods. Otherwise, our PhenoDriver can also effectively identify driver genes with both recurrent and rare mutations in individual patients. We further explore and reveal the oncogenic mechanisms of some known and unknown breast cancer driver genes (e.g. TP53, MAP3K1, HTT, etc.) identified by PhenoDriver, and construct their subnetworks for regulating clinical abnormal phenotypes. Notably, most of our findings are consistent with existing biological knowledge. Based on the personalized driver profiles, we discover two existing and one unreported breast cancer subtypes and uncover their molecular mechanisms. These results intensify our understanding for breast cancer mechanisms, guide therapeutic decisions and assist in the development of targeted anticancer therapies.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Oncogenes , Mutación , Fenotipo , InvestigaciónRESUMEN
Exposure of concrete to acidic environments can cause the degradation of concrete elements and seriously affect the durability of concrete. As solid wastes are produced during industrial activity, ITP (iron tailing powder), FA (fly ash), and LS (lithium slag) can be used as admixtures to produce concrete and improve its workability. This paper focuses on the preparation of concrete using a ternary mineral admixture system consisting of ITP, FA, and LS to investigate the acid erosion resistance of concrete in acetic acid solution at different cement replacement rates and different water-binder ratios. The tests were performed by compressive strength analysis, mass analysis, apparent deterioration analysis, and microstructure analysis by mercury intrusion porosimetry and scanning electron microscopy. The results show that when the water-binder ratio is certain and the cement replacement rate is greater than 16%; especially at 20%, the concrete shows strong resistance to acid erosion; when the cement replacement rate is certain and the water-binder ratio is less than 0.47; especially at 0.42, the concrete shows strong resistance to acid erosion. Microstructural analysis shows that the ternary mineral admixture system composed of ITP, FA, and LS promotes the formation of hydration products such as C-S-H and AFt, improves the compactness and compressive strength of concrete, and reduces the connected porosity of concrete, which can obtain good overall performance. In general, concrete prepared with a ternary mineral admixture system consisting of ITP, FA, and LS has better acid erosion resistance than ordinary concrete. The use of different kinds of solid waste powder to replace cement can effectively reduce carbon emissions and protect the environment.
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Predicting drug synergy is critical to tailoring feasible drug combination treatment regimens for cancer patients. However, most of the existing computational methods only focus on data-rich cell lines, and hardly work on data-poor cell lines. To this end, here we proposed a novel few-shot drug synergy prediction method (called HyperSynergy) for data-poor cell lines by designing a prior-guided Hypernetwork architecture, in which the meta-generative network based on the task embedding of each cell line generates cell line dependent parameters for the drug synergy prediction network. In HyperSynergy model, we designed a deep Bayesian variational inference model to infer the prior distribution over the task embedding to quickly update the task embedding with a few labeled drug synergy samples, and presented a three-stage learning strategy to train HyperSynergy for quickly updating the prior distribution by a few labeled drug synergy samples of each data-poor cell line. Moreover, we proved theoretically that HyperSynergy aims to maximize the lower bound of log-likelihood of the marginal distribution over each data-poor cell line. The experimental results show that our HyperSynergy outperforms other state-of-the-art methods not only on data-poor cell lines with a few samples (e.g., 10, 5, 0), but also on data-rich cell lines.
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Biología Computacional , Neoplasias , Humanos , Biología Computacional/métodos , Algoritmos , Teorema de Bayes , Neoplasias/tratamiento farmacológicoRESUMEN
Identifying cancer driver genes plays a curial role in the development of precision oncology and cancer therapeutics. Although a plethora of methods have been developed to tackle this problem, the complex cancer mechanisms and intricate interactions between genes still make the identification of cancer driver genes challenging. In this work, we propose a novel machine learning method of heterophilic graph diffusion convolutional networks (called HGDCs) to boost cancer-driver gene identification. Specifically, HGDC first introduces graph diffusion to generate an auxiliary network for capturing the structurally similar nodes in a biomolecular network. Then, HGDC designs an improved message aggregation and propagation scheme to adapt to the heterophilic setting of biomolecular networks, alleviating the problem of driver gene features being smoothed by its neighboring dissimilar genes. Finally, HGDC uses a layer-wise attention classifier to predict the probability of one gene being a cancer driver gene. In the comparison experiments with other existing state-of-the-art methods, our HGDC achieves outstanding performance in identifying cancer driver genes. The experimental results demonstrate that HGDC not only effectively identifies well-known driver genes on different networks but also novel candidate cancer genes. Moreover, HGDC can effectively prioritize cancer driver genes for individual patients. Particularly, HGDC can identify patient-specific additional driver genes, which work together with the well-known driver genes to cooperatively promote tumorigenesis.
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Neoplasias , Humanos , Neoplasias/genética , Redes Reguladoras de Genes , Medicina de Precisión , Oncogenes , Transformación Celular Neoplásica/genéticaRESUMEN
Identification of ncRNA-protein interactions (ncRPIs) through wet experiments is still time-consuming and highly-costly. Although several computational approaches have been developed to predict ncRPIs using the structure and sequence information of ncRNAs and proteins, the prediction accuracy needs to be improved, and the results lack interpretability. In this work, we proposed a novel computational method (called ncRPI-LGAT) to predict the ncRNA-Protein Interactions by transforming the link prediction (i.e., subgraph classification) task into a node classification task in the line network, and introducing a Line Graph ATtention network framework. ncRPI-LGAT first extracts the ncRNA/protein attributes using node2vec, and then generates the local enclosing subgraph of a target ncRNA-protein pair with SEAL. Because using the pooling operations in local enclosing subgraphs to learn a fixed-size feature vector for representing ncRNAs/proteins will cause the information loss, ncRPI-LGAT converts the local enclosing subgraphs into their corresponding line graphs, in which the node corresponds to the edge (i.e., ncRNA-protein pair) of the local enclosing subgraphs. Then, the attention mechanism-based graph neural network GATv2 is used on these line graphs to efficiently learn the embedding features of the target nodes (i.e., ncRNA-protein pairs) by focusing on learning the significance of one ncRNA-protein pair to another ncRNA-protein pair. These embedding features of one ncRNA-protein pair obtained from multi-head attention are concatenated in series and then fed them into a fully connected network to predict ncRPIs. Compared with other state-of-the-art methods in the 5CV test, ncRPI-LGAT shows superior performance on three benchmark datasets, demonstrating the effectiveness of our ncRPI-LGAT method in predicting ncRNA-protein interactions.
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Topologically associating domains (TADs) have emerged as basic structural and functional units of genome organization and have been determined by many computational methods from Hi-C contact maps. However, the TADs obtained by different methods vary greatly, which makes the accurate determination of TADs a challenging issue and hinders subsequent biological analyses about their organization and functions. Obvious inconsistencies among the TADs identified by different methods indeed make the statistical and biological properties of TADs overly depend on the chosen method rather than on the data. To this end, we use the consensus structural information captured by these methods to define the TAD separation landscape for decoding the consensus domain organization of the 3D genome. We show that the TAD separation landscape could be used to compare domain boundaries across multiple cell types for discovering conserved and divergent topological structures, decipher three types of boundary regions with diverse biological features, and identify consensus TADs (ConsTADs). We illustrate that these analyses could deepen our understanding of the relationships between the topological domains and chromatin states, gene expression, and DNA replication timing.
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Ensamble y Desensamble de Cromatina , Cromatina , Consenso , Cromatina/genética , Genoma , CromosomasRESUMEN
Single-cell Hi-C technology provides an unprecedented opportunity to reveal chromatin structure in individual cells. However, high sequencing cost impedes the generation of biological Hi-C data with high sequencing depths and multiple replicates for downstream analysis. Here, we developed a single-cell Hi-C simulator (scHi-CSim) that generates high-fidelity data for benchmarking. scHi-CSim merges neighboring cells to overcome the sparseness of data, samples interactions in distance-stratified chromosomes to maintain the heterogeneity of single cells, and estimates the empirical distribution of restriction fragments to generate simulated data. We demonstrated that scHi-CSim can generate high-fidelity data by comparing the performance of single-cell clustering and detection of chromosomal high-order structures with raw data. Furthermore, scHi-CSim is flexible to change sequencing depth and the number of simulated replicates. We showed that increasing sequencing depth could improve the accuracy of detecting topologically associating domains. We also used scHi-CSim to generate a series of simulated datasets with different sequencing depths to benchmark scHi-C clustering methods.
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Benchmarking , Cromatina , Cromatina/genética , CromosomasRESUMEN
Current machine learning-based methods have achieved inspiring predictions in the scenarios of mono-type and multi-type drug-drug interactions (DDIs), but they all ignore enhancive and depressive pharmacological changes triggered by DDIs. In addition, these pharmacological changes are asymmetric since the roles of two drugs in an interaction are different. More importantly, these pharmacological changes imply significant topological patterns among DDIs. To address the above issues, we first leverage Balance theory and Status theory in social networks to reveal the topological patterns among directed pharmacological DDIs, which are modeled as a signed and directed network. Then, we design a novel graph representation learning model named SGRL-DDI (social theory-enhanced graph representation learning for DDI) to realize the multitask prediction of DDIs. SGRL-DDI model can capture the task-joint information by integrating relation graph convolutional networks with Balance and Status patterns. Moreover, we utilize task-specific deep neural networks to perform two tasks, including the prediction of enhancive/depressive DDIs and the prediction of directed DDIs. Based on DDI entries collected from DrugBank, the superiority of our model is demonstrated by the comparison with other state-of-the-art methods. Furthermore, the ablation study verifies that Balance and Status patterns help characterize directed pharmacological DDIs, and that the joint of two tasks provides better DDI representations than individual tasks. Last, we demonstrate the practical effectiveness of our model by a version-dependent test, where 88.47 and 81.38% DDI out of newly added entries provided by the latest release of DrugBank are validated in two predicting tasks respectively.
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Aprendizaje Automático , Redes Neurales de la Computación , Interacciones FarmacológicasRESUMEN
Identification of cancer driver genes plays an important role in precision oncology research, which is helpful to understand cancer initiation and progression. However, most existing computational methods mainly used the protein-protein interaction (PPI) networks, or treated the directed gene regulatory networks (GRNs) as the undirected gene-gene association networks to identify the cancer driver genes, which will lose the unique structure regulatory information in the directed GRNs, and then affect the outcome of the cancer driver gene identification. Here, based on the multi-omics pan-cancer data (i.e., gene expression, mutation, copy number variation, and DNA methylation), we propose a novel method (called DGMP) to identify cancer driver genes by jointing directed graph convolutional network (DGCN) and multilayer perceptron (MLP). DGMP learns the multi-omics features of genes as well as the topological structure features in GRN with the DGCN model and uses MLP to weigh more on gene features for mitigating the bias toward the graph topological features in the DGCN learning process. The results on three GRNs show that DGMP outperforms other existing state-of-the-art methods. The ablation experimental results on the DawnNet network indicate that introducing MLP into DGCN can offset the performance degradation of DGCN, and jointing MLP and DGCN can effectively improve the performance of identifying cancer driver genes. DGMP can identify not only the highly mutated cancer driver genes but also the driver genes harboring other kinds of alterations (e.g., differential expression and aberrant DNA methylation) or genes involved in GRNs with other cancer genes. The source code of DGMP can be freely downloaded from https://github.com/NWPU-903PR/DGMP.
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Neoplasias , Humanos , Neoplasias/genética , Multiómica , Variaciones en el Número de Copia de ADN , Medicina de Precisión , Genómica/métodos , Redes Reguladoras de Genes , Redes Neurales de la ComputaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Pyrolae herba is the dried whole plant of Pyrola calliantha H. Andres or Pyrola decorata H. Andres (Pyrolaceae). Pyrolae herba has a long history of medicinal use in China. In ancient times, it was often used to treat pain in tendons and bones, swollen sore, cough, expectoration, bleeding, and other diseases. and was commonly used in ancient times to treat pain in the tendons and bones, swollen sore, cough, expectoration, bleeding and other diseases. AIM OF THE REVIEW: This paper summarizes the botany, traditional uses, phytochemistry, pharmacology, quality control and toxicology of Pyrolae herba, with a view to providing reference for further development and research. MATERIALS AND METHODS: The relevant information on Pyrolae herba was collected from the scientific databases including PubMed, CNKI, ScienceDirect, Wiley, Springer, Web of Science, Google Scholar, Baidu Scholar, Pharmacopoeia of the People's Republic of China and Flora Republicae Popularis Sinicae, etc. RESULTS: At present, more than 70 compounds have been identified from Pyrolae herba, including flavonoids, phenolic glycosides, quinones, terpenoids, volatile oils and other compounds. Pharmacological studies have shown that Pyrolae herba has a variety of pharmacological activities, such as anti-inflammatory, anti-bacterial, anti-viral, anti-tumor, anti-oxidation, reducing blood lipids, protective on cardiovascular and cerebrovascular, promoting osteoblast proliferation, and so on. It is used clinically in modern times to treat rheumatic arthritis, rheumatoid arthritis, bone hyperplasia, sciatica, cervical spondylosis, lumbar spondylosis, acute and chronic bronchitis, mammary gland hyperplasia, tumor, hypertension, coronary heart disease and bleeding diseases. CONCLUSIONS: Pyrolae herba is rich in chemical constituents, diverse in pharmacological activities and abundant in resources, which is widely used in clinics from traditional to modern. However, there is a lack of research on the relationship between chemical constituents and pharmacodynamics of Pyrolae herba. In addition, the existing clinical applications suggest that Pyrolae herba has a certain therapeutic potential in the treatment of hemorrhagic diseases, but there is a lack of information on experimental studies. It is worthwhile to further investigate the Pyrolae herba in depth in the hope of making discoveries and breakthroughs.
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Botánica , Medicamentos Herbarios Chinos , Tos/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Etnofarmacología , Humanos , Hiperplasia/tratamiento farmacológico , Medicina Tradicional China , Dolor/tratamiento farmacológico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Control de CalidadRESUMEN
BACKGROUND: Cancer is a heterogeneous disease in which tumor genes cooperate as well as adapt and evolve to the changing conditions for individual patients. It is a meaningful task to discover the personalized cancer driver genes that can provide diagnosis and target drug for individual patients. However, most of existing methods mainly ranks potential personalized cancer driver genes by considering the patient-specific nodes information on the gene/protein interaction network. These methods ignore the personalized edge weight information in gene interaction network, leading to false positive results. RESULTS: In this work, we presented a novel algorithm (called PDGPCS) to predict the Personalized cancer Driver Genes based on the Prize-Collecting Steiner tree model by considering the personalized edge weight information. PDGPCS first constructs the personalized weighted gene interaction network by integrating the personalized gene expression data and prior known gene/protein interaction network knowledge. Then the gene mutation data and pathway data are integrated to quantify the impact of each mutant gene on every dysregulated pathway with the prize-collecting Steiner tree model. Finally, according to the mutant gene's aggregated impact score on all dysregulated pathways, the mutant genes are ranked for prioritizing the personalized cancer driver genes. Experimental results on four TCGA cancer datasets show that PDGPCS has better performance than other personalized driver gene prediction methods. In addition, we verified that the personalized edge weight of gene interaction network can improve the prediction performance. CONCLUSIONS: PDGPCS can more accurately identify the personalized driver genes and takes a step further toward personalized medicine and treatment. The source code of PDGPCS can be freely downloaded from https://github.com/NWPU-903PR/PDGPCS .
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Redes Reguladoras de Genes , Neoplasias , Medicina de Precisión , Algoritmos , Humanos , Mutación , Neoplasias/diagnóstico , Neoplasias/genética , OncogenesRESUMEN
As the most abundant RNA modification, N6-methyladenosine (m6A) plays an important role in various RNA activities including gene expression and translation. With the rapid application of MeRIP-seq technology, samples of multiple groups, such as the involved multiple viral/ bacterial infection or distinct cell differentiation stages, are extracted from same experimental unit. However, our current knowledge about how the dynamic m6A regulating gene expression and the role in certain biological processes (e.g. immune response in this complex context) is largely elusive due to lack of effective tools. To address this issue, we proposed a Bayesian hierarchical mixture model (called m6Aexpress-BHM) to predict m6A regulation of gene expression (m6A-reg-exp) in multiple groups of MeRIP-seq experiment with limited samples. Comprehensive evaluations of m6Aexpress-BHM on the simulated data demonstrate its high predicting precision and robustness. Applying m6Aexpress-BHM on three real-world datasets (i.e. Flaviviridae infection, infected time-points of bacteria and differentiation stages of dendritic cells), we predicted more m6A-reg-exp genes with positive regulatory mode that significantly participate in innate immune or adaptive immune pathways, revealing the underlying mechanism of the regulatory function of m6A during immune response. In addition, we also found that m6A may influence the expression of PD-1/PD-L1 via regulating its interacted genes. These results demonstrate the power of m6Aexpress-BHM, helping us understand the m6A regulatory function in immune system.
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Adenosina , ARN , Adenosina/genética , Adenosina/metabolismo , Teorema de Bayes , Regulación de la Expresión Génica , Metilación , ARN/genéticaRESUMEN
The treatment of complex diseases by using multiple drugs has become popular. However, drug-drug interactions (DDI) may give rise to the risk of unanticipated adverse effects and even unknown toxicity. Therefore, for polypharmacy safety it is crucial to identify DDIs and explore their underlying mechanisms. The detection of DDI in the wet lab is expensive and time-consuming, due to the need for experimental research over a large volume of drug combinations. Although many computational methods have been developed to predict DDIs, most of these are incapable of predicting potential DDIs between drugs within the DDI network and new drugs from outside the DDI network. In addition, they are not designed to explore the underlying mechanisms of DDIs and lack interpretative capacity. Thus, here we propose a novel method of GNN-DDI to predict potential DDIs by constructing a five-layer graph attention network to identify k-hops low-dimensional feature representations for each drug from its chemical molecular graph, concatenating all identified features of each drug pair, and inputting them into a MLP predictor to obtain the final DDI prediction score. The experimental results demonstrate that our GNN-DDI is suitable for each of two DDI predicting scenarios, namely the potential DDIs among known drugs in the DDI network and those between drugs within the DDI network and new drugs from outside DDI network. The case study indicates that our method can explore the specific drug substructures that lead to the potential DDIs, which helps to improve interpretability and discover the underlying interaction mechanisms of drug pairs.