IET Systems Biology
Volume 8, Issue 2, April 2014
Volumes & issues:
Volume 8, Issue 2
April 2014
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- Author(s): Xing-Ming Zhao
- Source: IET Systems Biology, Volume 8, Issue 2, page: 23 –23
- DOI: 10.1049/iet-syb.2014.0005
- Type: Article
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- Author(s): Yuanning Liu ; Minghui Wang ; Huanqing Feng ; Ao Li
- Source: IET Systems Biology, Volume 8, Issue 2, p. 24 –32
- DOI: 10.1049/iet-syb.2013.0027
- Type: Article
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The authors describe an integrated method for analysing cancer driver aberrations and disrupted pathways by using tumour single nucleotide polymorphism (SNP) arrays. The authors new method adopts a novel statistical model to explicitly quantify the SNP signals, and therefore infers the genomic aberrations, including copy number alteration and loss of heterozygosity. Examination on the dilution series dataset shows that this method can correctly identify the genomic aberrations even with the existence of severe normal cell contamination in tumour sample. Furthermore, with the results of the aberration identification obtained from multiple tumour samples, a permutation-based approach is proposed for identifying the statistically significant driver aberrations, which are further incorporated with the known signalling pathways for pathway enrichment analysis. By applying the approach to 286 hepatocellular tumour samples, they successfully uncover numerous driver aberration regions across the cancer genome, for example, chromosomes 4p and 5q, which harbour many known hepatocellular cancer related genes such as alpha-fetoprotein (AFP) and ectodermal-neural cortex (ENC1). In addition, they identify nine disrupted pathways that are highly enriched by the driver aberrations, including the systemic lupus erythematosus pathway, the vascular endothelial growth factor (VEGF) signalling pathway and so on. These results support the feasibility and the utility of the proposed method on the characterisation of the cancer genome and the downstream analysis of the driver aberrations and the disrupted signalling pathways.
- Author(s): Jiaxin Wu ; Silu Yang ; Rui Jiang
- Source: IET Systems Biology, Volume 8, Issue 2, p. 33 –40
- DOI: 10.1049/iet-syb.2013.0033
- Type: Article
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Detecting associations between human genetic variants and their phenotypic effects is a significant problem in understanding genetic bases of human-inherited diseases. The focus is on a typical type of genetic variants called non-synonymous single nucleotide polymorphisms (nsSNPs), whose occurrence may potentially alter the structures of proteins, affecting functions of proteins, and thereby causing diseases. Most of the existing methods predict associations between nsSNPs and diseases based on features derived from only protein sequence and/or structure information, and give no information about which specific disease an nsSNP is associated with. To cope with these problems, the identification of nsSNPs that are associated with a specific disease from a set of candidate nsSNPs as a binary classification problem has been formulated. A new approach has been adopted for predicting associations between nsSNPs and diseases based on multiple nsSNP similarity networks and disease phenotype similarity networks. With a series of comprehensive validation experiments, it has been demonstrated that the proposed method is effective in both recovering the nsSNP-disease associations and inferring suspect disease-associated nsSNPs for both diseases with known genetic bases and diseases of unknown genetic bases.
- Author(s): Yichuan Wang ; Haiyang Fang ; Tinghong Yang ; Duzhi Wu ; Jing Zhao
- Source: IET Systems Biology, Volume 8, Issue 2, p. 41 –46
- DOI: 10.1049/iet-syb.2013.0038
- Type: Article
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Computational methods play an important role in the disease genes prioritisation by integrating many kinds of data sources such as gene expression, functional annotations and protein–protein interactions. However, the existing methods usually perform well in predicting highly linked genes, whereas they work quite poorly for loosely linked genes. Motivated by this observation, a degree-adjusted strategy is applied to improve the algorithm that was proposed earlier for the prediction of disease genes from gene expression and protein interactions. The authors also showed that the modified method is good at identifying loosely linked disease genes and the overall performance gets enhanced accordingly. This study suggests the importance of statistically adjusting the degree distribution bias in the background network for network-based modelling of complex diseases.
- Author(s): Xiaochen Wang ; Huajie Qian ; Shuqin Zhang
- Source: IET Systems Biology, Volume 8, Issue 2, p. 47 –55
- DOI: 10.1049/iet-syb.2013.0041
- Type: Article
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Discovering significant pathways rather than single genes or small gene sets involved in metastasis is becoming more and more important in the study of breast cancer. Many researches have shed light on this problem. However, most of the existing works are relying on some priori biological information, which may bring bias to the models. The authors propose a new method that detects metastasis-related pathways by identifying and comparing modules in metastasis and non-metastasis gene co-expression networks. The gene co-expression networks are built by Pearson correlation coefficients, and then the modules inferred in these two networks are compared. In metastasis and non-metastasis networks, 36 and 41 significant modules are identified. Also, 27.8% (metastasis) and 29.3% (non-metastasis) of the modules are enriched significantly for one or several pathways with p-value <0.05. Many breast cancer genes including RB1, CCND1 and TP53 are included in these identified pathways. Five significant pathways are discovered only in metastasis network: glycolysis pathway, cell adhesion molecules, focal adhesion, stathmin and breast cancer resistance to antimicrotubule agents, and cytosolic DNA-sensing pathway. The first three pathways have been proved to be closely associated with metastasis. The rest two can be taken as a guide for future research in breast cancer metastasis.
- Author(s): Chien-Hung Huang ; Min-You Wu ; Peter Mu-Hsin Chang ; Chi-Ying Huang ; Ka-Lok Ng
- Source: IET Systems Biology, Volume 8, Issue 2, p. 56 –66
- DOI: 10.1049/iet-syb.2013.0035
- Type: Article
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Lung cancer is one of the leading causes of death in both the USA and Taiwan, and it is thought that the cause of cancer could be because of the gain of function of an oncoprotein or the loss of function of a tumour suppressor protein. Consequently, these proteins are potential targets for drugs. In this study, differentially expressed genes are identified, via an expression dataset generated from lung adenocarcinoma tumour and adjacent non-tumour tissues. This study has integrated many complementary resources, that is, microarray, protein-protein interaction and protein complex. After constructing the lung cancer protein-protein interaction network (PPIN), the authors performed graph theory analysis of PPIN. Highly dense modules are identified, which are potential cancer-associated protein complexes. Up- and down-regulated communities were used as queries to perform functional enrichment analysis. Enriched biological processes and pathways are determined. These sets of up- and down-regulated genes were submitted to the Connectivity Map web resource to identify potential drugs. The authors' findings suggested that eight drugs from DrugBank and three drugs from NCBI can potentially reverse certain up- and down-regulated genes' expression. In conclusion, this study provides a systematic strategy to discover potential drugs and target genes for lung cancer.
- Author(s): Limin Li
- Source: IET Systems Biology, Volume 8, Issue 2, p. 67 –73
- DOI: 10.1049/iet-syb.2013.0040
- Type: Article
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Identifying drug–target interactions has been a key step for drug repositioning, drug discovery and drug design. Since it is expensive to determine the interactions experimentally, computational methods are needed for predicting interactions. In this work, the authors first propose a single-view penalised graph (SPGraph) clustering approach to integrate drug structure and protein sequence data in a structural view. The SPGraph model does clustering on drugs and targets simultaneously such that the known drug–target interactions are best preserved in the clustering results. They then apply the SPGraph to a chemical view with drug response data and gene expression data in NCI-60 cell lines. They further generalise the SPGraph to a multi-view penalised graph (MPGraph) version, which can integrate the structural view and chemical view of the data. In the authors' experiments, they compare their approach with some comparison partners, and the results show that the SPGraph could improve the prediction accuracy in a small scale, and the MPGraph can achieve around 10% improvements for the prediction accuracy. They finally give some new targets for 22 Food and Drug Administration approved drugs for drug repositioning, and some can be supported by other references.
Editorial: Part 1: Network biology in translational bioinformatics and systems biology
Comprehensive study of tumour single nucleotide polymorphism array data reveals significant driver aberrations and disrupted signalling pathways in human hepatocellular cancer
Inferring non-synonymous single-nucleotide polymorphisms-disease associations via integration of multiple similarity networks
Degree-adjusted algorithm for prioritisation of candidate disease genes from gene expression and protein interactome
Discovery of significant pathways in breast cancer metastasis via module extraction and comparison
In silico identification of potential targets and drugs for non-small cell lung cancer
MPGraph: multi-view penalised graph clustering for predicting drug–target interactions
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