BackgroundProstate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer.ResultsTo deal with missing values in microarray data, we used a K-nearest-neighbors (KNN) algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD) as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2) regulated by RUNX1 and STAT3 is correlated to the pathological stage.ConclusionsWe provide a computational framework to reconstruct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences. Our method is helpful in verifying possible interaction relations in gene regulatory networks and filtering out incorrect relations inferred by imperfect methods. We predicted not only individual gene related to cancer but also discovered significant gene regulation networks. Our method is also validated in several enriched published papers and databases and the significant gene regulatory networks perform critical biological functions and processes including cell adhesion molecules, androgen and estrogen metabolism, smooth muscle contraction, and GO-annotated processes. Those significant gene regulations and the critical concept of tumor progression are useful to understand cancer biology and disease treatment.
Polyacrylonitrile-based activated carbon fibers (ACFs), modified using potassium hydroxide (KOH) or tetraethylenepentamine (TEPA), were investigated for carbon dioxide (CO2) adsorption, which is one of the promising alleviation approaches for global warming. The CO2 adsorption isotherms were measured, and the values of isosteric heat of adsorption were calculated. The results showed that the KOH-modified ACFs exhibited a great deal of pore volume, and a specific surface area of 1565 m2/g was obtained. KOH activation made nitrogen atoms easily able to escape from the surface of ACFs. On the other hand, the surface area and pore volume of ACFs modified with TEPA were significantly reduced, which can be attributed to the closing or blocking of micropores by the N-groups. The CO2 adsorption on the ACF samples was via exothermic reactions and was a type of physical adsorption, where the CO2 adsorption occurred on heterogeneous surfaces. The CO2 uptakes at 1 atm and 25 °C on KOH-activated ACFs reached 2.74 mmole/g. This study observed that microporosity and surface oxygen functionalities were highly associated with the CO2 uptake, implying the existence of O-C coordination, accompanied with physical adsorption. Well cyclability of the adsorbents for CO2 adsorption was observed, with a performance decay of less than 5% over up to ten adsorption-desorption cycles.
Obstructive sleep apnea (OSA) has been a common sleep disorder for years, and polysomnography (PSG) remains the gold standard for diagnosing OSA. Nevertheless, PSG is a time and money consuming test, and patients have to wait long for arranging a PSG test in a hospital. In light of this, portable and wearable tools for OSA classification have been developed recently as a low‐cost and easy‐to‐use screening method before undergoing PSG. Using unsegmented electrocardiogram (ECG) signals, a deep neural network (DNN)‐based model is developed here to categorize OSA severity with the following features. First, the model takes unsegmented ECG signals recorded overnight as input, and then generates a four‐level scale as output. Since all the input ECG signals are unsegmented, the tremendous amount of effort spent on signal annotation can be fully saved. Second, the largest amount of data is used to test the model and consequently provide a high generalization ability, as compared with others in the literature. The overall outperformance of this work is highlighted at the end of this article, and this work is validated as an easy‐to‐use and effective screening tool for OSA accordingly.
BackgroundDrug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, wet-lab approaches alone to counter drug resistance have so far still achieved limited success due to less knowledge about the underlying mechanisms of drug resistance. Our approach apply a heuristic search algorithm in order to extract active network under drug treatment and use a random walk model to identify potential co-targets for effective antibacterial drugs.ResultsWe use interactome network of Mycobacterium tuberculosis and gene expression data which are treated with two kinds of antibiotic, Isoniazid and Ethionamide as our test data. Our analysis shows that the active drug-treated networks are associated with the trigger of fatty acid metabolism and synthesis and nicotinamide adenine dinucleotide (NADH)-related processes and those results are consistent with the recent experimental findings. Efflux pumps processes appear to be the major mechanisms of resistance but SOS response is significantly up-regulation under Isoniazid treatment. We also successfully identify the potential co-targets with literature confirmed evidences which are related to the glycine-rich membrane, adenosine triphosphate energy and cell wall processes.ConclusionsWith gene expression and interactome data supported, our study points out possible pathways leading to the emergence of drug resistance under drug treatment. We develop a computational workflow for giving new insights to bacterial drug resistance which can be gained by a systematic and global analysis of the bacterial regulation network. Our study also discovers the potential co-targets with good properties in biological and graph theory aspects to overcome the problem of drug resistance.
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