IET Systems Biology最新文献

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.

This study aims to discover the genetic modules that distinguish glioblastoma multiforme (GBM) from low-grade glioma (LGG) and identify hub genes. A co-expression network is constructed using the expression profiles of 28 GBM and LGG patients from the Gene Expression Omnibus database. The authors performed gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) analysis on these genes. The maximal clique centrality method was used to identify hub genes. Online tools were employed to confirm the link between hub gene expression and overall patient survival rate. The top 5000 genes with major variance were classified into 18 co-expression gene modules. GO analysis indicated that abnormal changes in ‘cell migration’ and ‘collagen metabolic process’ were involved in the development of GBM. KEGG analysis suggested that ‘focal adhesion’ and ‘p53 signalling pathway’ regulate the tumour progression. TNFAIP6 was identified as a hub gene, and the expression of TNFAIP6 was increased with the elevation of pathological grade. Survival analysis indicated that the higher the expression of TNFAIP6, the shorter the survival time of patients. The authors identified TNFAIP6 as the hub gene in the progression of GBM, and its high expression indicates the poor prognosis of the patients.

Acute paraquat poisoning is due to the extremely severe toxicity of paraquat. After paraquat enters the human body, it will cause rapid changes in the human body system. Since paraquat poisoning will quickly invade the organs of the whole body, it may cause damage to the functions of multiple organs in the poisoned patient. The liver organ is the most important detoxification site for the human body, so the damage to the liver of the patient is more obvious. This article discovers and observes the structure of paraquat and the dynamic changes of serum cytokines in patients with paraquat poisoning through the clinical phenomenon of paraquat poisoning, and the related changes of human serum cells after the subjects took paraquat and the changes of cell dynamic factors after different doses of paraquat entered the human body were analysed. At the same time, the changes in the immune function of the body of different groups of people were also observed. The experimental results in this article show that according to the intake of paraquat, the severity of poisoning patients will be mild, moderate, severe and outbreak poisoning. Among them, the dose for adults who cannot be treated for prognosis is 10 ml.

The cingulate cortex is part of the conserved limbic system, which is considered as a hub of emotional and cognitive control. Accumulating evidence suggested that involvement of the cingulate cortex is significant for cognitive impairment of Parkinson's disease (PD). However, mechanistic studies of the cingulate cortex in PD pathogenesis are limited. Here, transcriptomic and regulatory network analyses were conducted for the cingulate cortex in PD. Enrichment and clustering analyses showed that genes involved in regulation of membrane potential and glutamate receptor signalling pathway were upregulated. Importantly, myelin genes and the oligodendrocyte development pathways were markedly downregulated, indicating disrupted myelination in PD cingulate cortex. Cell-type-specific signatures revealed that myelinating oligodendrocytes were the major cell type damaged in the PD cingulate cortex. Furthermore, downregulation of myelination pathways in the cingulate cortex were shared and validated in another independent RNAseq cohort of dementia with Lewy bodies (DLB). In combination with ATACseq data, gene regulatory networks (GRNs) were further constructed for 32 transcription factors (TFs) and 466 target genes among differentially expressed genes (DEGs) using a tree-based machine learning algorithm. Several transcription factors, including Olig2, Sox8, Sox10, E2F1, and NKX6-2, were highlighted as key nodes in a sub-network, which control many overlapping downstream targets associated with myelin formation and gliogenesis. In addition, the authors have validated a subset of DEGs by qPCRs in two PD mouse models. Notably, seven of these genes,TOX3, NECAB2 NOS1, CAPN3, NR4A2, E2F1 and FOXP2, have been implicated previously in PD or neurodegeneration and are worthy of further studies as novel candidate genes. Together, our findings provide new insights into the role of remyelination as a promising new approach to treat PD after demyelination.

Prenatal karyotype diagnosis is important to determine if the foetus has genetic diseases and some congenital diseases. Chromosome classification is an important part of karyotype analysis, and the task is tedious and lengthy. Chromosome classification methods based on deep learning have achieved good results, but if the quality of the chromosome image is not high, these methods cannot learn image features well, resulting in unsatisfactory classification results. Moreover, the existing methods generally have a poor effect on sex chromosome classification. Therefore, in this work, the authors propose to use a super-resolution network, Self-Attention Negative Feedback Network, and combine it with traditional neural networks to obtain an efficient chromosome classification method called SRAS-net. The method first inputs the low-resolution chromosome images into the super-resolution network to generate high-resolution chromosome images and then uses the traditional deep learning model to classify the chromosomes. To solve the problem of inaccurate sex chromosome classification, the authors also propose to use the SMOTE algorithm to generate a small number of sex chromosome samples to ensure a balanced number of samples while allowing the model to learn more sex chromosome features. Experimental results show that our method achieves 97.55% accuracy and is better than state-of-the-art methods.