IET Systems Biology最新文献

The most common type of lung cancer tissue is lung adenocarcinoma. The TCGA-LUAD cohort retrieved from the TCGA dataset was considered the internal training cohort, while GSE68465 and GSE13213 datasets from the GEO database were used as the external test cohort. The TCGA-LUAD cohort was classified into two immune subtypes using single-sample gene set enrichment analysis of the immune gene set and unsupervised clustering analysis. The ESTIMATE algorithm, the CIBERSORT algorithm, and HLA family expression levels again validated the reliability of this typing. We performed Venn analysis using immune-related genes from the immport dataset and differentially expressed genes from the subtypes to retrieve differentially expressed immune genes (DEIGs). In addition, DEIGs were used to construct a prognostic model with the least absolute shrinkage and selection operator regression analysis. A reliable risk model consisting of 11 DEIGs, including S100P, INHA, SEMA7A, INSL4, CD40LG, AGER, SERPIND1, CD1D, CX3CR1, SFTPD, and CD79A, was then built, and its reliability was further confirmed by ROC curve and calibration plot analysis. The high-risk score subgroup had a poor prognosis and a lower tumour immune dysfunction and exclusion score, indicating a greater likelihood of anti-PD-1/cytotoxic T lymphocyte antigen 4 benefit.

The correlation between dysregulation of splicing and cancers has been increasingly recognised and confirmed. The identification of valuable alternative splicing (AS) in pancreatic head cancer (PHC) has a great significance. AS profiles in PHC were generated using the data from The Cancer Genome Atlas and TCGASpliceSeq. Then, the NMF clustering method was performed to identify overall survival-associated AS (OS-AS) subtypes in PHC patients. Subsequently, we used least absolute shrinkage and selection operator Cox regression analysis to construct an AS-related risk model. The splicing regulatory network was uncovered by Cytoscape 3.7. A total of 1694 OS-AS events were obtained. The PHC patients were divided into clusters 1 and 2. Cluster 1 had poorer prognosis and lower infiltration of immune cells. Subsequently, a prognostic signature was established that showed good performance in predicting OS and progression-free survival. The risk score of this signature was associated with the unique tumour immunity. Moreover, a nomogram incorporating the risk score and clinicopathological parameters was established. Finally, a splicing factor-AS regulatory network was developed. A comprehensive analysis of the AS events in PHC associated with prognosis and tumour immunity may help provide reliable information to guide individual treatment strategies.

Sparse and noisy measurements make parameter estimation for biochemical reaction networks difficult and might lead to ill-posed optimisation problems. This is potentiated if the data has to be normalised, and only fold changes rather than absolute amounts are available. Here, the authors consider the propagation of measurement noise to the distribution of the maximum likelihood (ML) estimator in an in silico study. Therefore, a model of a reversible reaction is considered, for which reaction rate constants using fold changes is estimated. Noise propagation is analysed for different normalisation strategies and different error models. In particular, accuracy, precision, and asymptotic properties of the ML estimator is investigated. Results show that normalisation by the mean of a time series outperforms normalisation by a single time point in the example provided by the authors. Moreover, the error model with a heavy-tail distribution is slightly more robust to large measurement noise, but, beyond this, the choice of the error model did not have a significant impact on the estimation results provided by the authors.

Burkitt lymphoma (BL) is one of the most aggressive forms of non-Hodgkin's lymphomas that affect children and young adults. The expression of genes and other molecular markers during carcinogenesis can be the basis for diagnosis, prognosis and the design of new and effective drugs for the management of cancers. The aim of this study was to identify genes that can serve as prognostic and therapeutic targets for BL. We analysed RNA-seq data of BL transcriptome sequencing projects in Africa using standard RNA-seq analyses pipeline. We performed pathway enrichment analyses, protein–protein interaction networks, gene co-expression and survival analyses. Gene and pathway enrichment analyses showed that the differentially expressed genes are involved in tube development, signalling receptor binding, viral protein interaction, cell migration, external stimuli response, serine hydrolase activity and PI3K-Akt signalling pathway. Protein–protein interaction network analyses revealed the genes to be highly interconnected, whereas module analyses revealed 25 genes to possess the highest interaction score. Overall survival analyses delineated six genes (ADAMTSL4, SEMA5B, ADAMTS15, THBS2, SPON1 and THBS1) that can serve as biomarkers for prognosis for BL management.

The authors wish to bring to the readers' attention the following errors in the article by Jin Zhang and Shan Ju, ‘Identifying genuine protein–protein interactions within communities of gene co-expression networks using a deconvolution method’.

In Section 5 Acknowledgements, one grant/award number was omitted. ‘XBS’ should be ‘XBS1822’.

In this paper, the side effects of drug therapy in the process of cancer treatment are reduced by designing two optimal non-linear controllers. The related gains of the designed controllers are optimised using genetic algorithm and simultaneously are adapted by employing the Fuzzy scheduling method. The cancer dynamic model is extracted with five differential equations, including normal cells, endothelial cells, cancer cells, and the amount of two chemotherapy and anti-angiogenic drugs left in the body as the engaged state variables, while double drug injection is considered as the corresponding controlling signals of the mentioned state space. This treatment aims to reduce the tumour cells by providing a timely schedule for drug dosage. In chemotherapy, not only the cancer cells are killed but also other healthy cells will be destroyed, so the rate of drug injection is highly significant. It is shown that the simultaneous application of chemotherapy and anti-angiogenic therapy is more efficient than single chemotherapy. Two different non-linear controllers are employed and their performances are compared. Simulation results and comparison studies show that not only adding the anti-angiogenic reduce the side effects of chemotherapy but also the proposed robust controller of sliding mode provides a faster and stronger treatment in the presence of patient parametric uncertainties in an optimal way. As a result of the proposed closed-loop drug treatment, the tumour cells rapidly decrease to zero, while the normal cells remain healthy simultaneously. Also, the injection rate of the chemotherapy drug is very low after a short time and converges to zero.

The development of sequencing technology has promoted the expansion of cancer genome data. It is necessary to identify the pathogenesis of cancer at the molecular level and explore reliable treatment methods and precise drug targets in cancer by identifying carcinogenic functional modules in massive multi-omics data. However, there are still limitations to identifying carcinogenic driver modules by utilising genetic characteristics simply. Therefore, this study proposes a computational method, NetAP, to identify driver modules in prostate cancer. Firstly, high mutual exclusivity, high coverage, and high topological similarity between genes are integrated to construct a weight function, which calculates the weight of gene pairs in a biological network. Secondly, the random walk method is utilised to reevaluate the strength of interaction among genes. Finally, the optimal driver modules are identified by utilising the affinity propagation algorithm. According to the results, the authors’ method identifies more validated driver genes and driver modules compared with the other previous methods. Thus, the proposed NetAP method can identify carcinogenic driver modules effectively and reliably, and the experimental results provide a powerful basis for cancer diagnosis, treatment and drug targets.

Alopecia Areata (AA) is characterised by an autoimmune response to hair follicles (HFs) and its exact pathobiology remains unclear. The current study aims to look into the molecular changes in the skin of AA patients as well as the potential underlying molecular mechanisms of AA in order to identify potential candidates for early detection and treatment of AA. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules, hub genes, and mRNA–miRNA regulatory networks associated with AA. Furthermore, Chi2 as a machine-learning algorithm was used to compute the gene importance in AA. Finally, drug-target construction revealed the potential of repositioning drugs for the treatment of AA. Our analysis using four AA data sets established a network strongly correlated to AA pathogenicity based on GZMA, OXCT2, HOXC13, KRT40, COMP, CHAC1, and KRT83 hub genes. Interestingly, machine learning introduced these genes as important in AA pathogenicity. Besides that, using another ten data sets, we showed that CHAC1 could clearly distinguish AA from similar clinical phenotypes, such as scarring alopecia due to psoriasis. Also, two FDA-approved drug candidates and 30 experimentally validated miRNAs were identified that affected the co-expression network. Using transcriptome analysis, suggested CHAC1 as a potential diagnostic predictor to diagnose AA.

In practice, there are many physical systems that can have only positive inputs, such as physiological systems. Most conventional control methods cannot ensure that the main system input is positive. A positive input observer-based controller is designed for an intravenous glucose tolerance test model of type 1 diabetes mellitus (T1DM). The backstepping (BS) approach is employed to design the feedback controller for artificial pancreas (AP) systems, based on the Extended Bergman's Minimal Model (EBMM). The EBMM represents the T1DM in terms of the blood glucose concentration (BGC), insulin concentration, and plasma level and the disturbance of insulin during medication due to either meal intake or burning sugar by doing some physical exercise. The insulin concentration and plasma level are estimated using observers, and these estimations are applied as feedback to the controller. The asymptotic stability of the observer-based controller is proved using the Lyapunov theorem. Moreover, it is proved that the system is bounded input-bounded output (BIBO) stable in the presence of uncertainties generated by uncertain parameters and external disturbance. For realistic situations, we consider only the BGC to be available for measurement and additionally inter-and intra-patient variability of system parameters is considered.

Malignancies and diseases of various genetic origins can be diagnosed and classified with microarray data. There are many obstacles to overcome due to the large size of the gene and the small number of samples in the microarray. A combination strategy for gene expression in a variety of diseases is described in this paper, consisting of two steps: identifying the most effective genes via soft ensembling and classifying them with a novel deep neural network. The feature selection approach combines three strategies to select wrapper genes and rank them according to the k-nearest neighbour algorithm, resulting in a very generalisable model with low error levels. Using soft ensembling, the most effective subsets of genes were identified from three microarray datasets of diffuse large cell lymphoma, leukaemia, and prostate cancer. A stacked deep neural network was used to classify all three datasets, achieving an average accuracy of 97.51%, 99.6%, and 96.34%, respectively. In addition, two previously unreported datasets from small, round blue cell tumors (SRBCTs)and multiple sclerosis-related brain tissue lesions were examined to show the generalisability of the model method.