Extracting Sub-Networks from Brain Functional Network Using Graph Regularized Nonnegative Matrix Factorization

Currently,functional connectomes constructed from neuroimaging data have emerged as a powerful tool in identifying brain disorders.If one brain disease just manifests as some cognitive dysfunction,it means that the disease may affect some local connectivity in the brain functional network.That is,there are functional abnormalities in the sub-network.Therefore,it is crucial to accurately identify them in pathological diagnosis.To solve these problems,we proposed a sub-network extraction method based on graph regularization nonnegative matrix factorization(GNMF).The dynamic functional networks of normal subjects and early mild cognitive impairment(eMCI)subjects were vectorized and the functional connection vectors(FCV)were assembled to aggregation matrices.Then GNMF was applied to factorize the aggregation matrix to get the base matrix,in which the column vectors were restored to a common sub-network and a distinctive sub-network,and visualization and statistical analysis were conducted on the two sub-networks,respectively.Experimental results demonstrated that,compared with other matrix factorization methods,the proposed method can more obviously reflect the similarity between the common subnetwork of eMCI subjects and normal subjects,as well as the difference between the distinctive sub-network of eMCI subjects and normal subjects,Therefore,the high-dimensional features in brain functional networks can be best represented locally in the lowdimensional space,which provides a new idea for studying brain functional connectomes.

Mining Functional Gene Modules Linked with Rheumatoid Arthritis Using a SNP-SNP Network

The identification of functional gene modules that are derived from integration of information from different types of networks is a powerful strategy for interpreting the etiology of complex diseases such as rheumatoid arthritis （RA）. Genetic variants are known to increase the risk of developing RA. Here, a novel method, the construction of a genetic network, was used to mine functional gene modules linked with RA. A polymorphism interaction analy- sis （PIA） algorithm was used to obtain cooperating single nucleotide polymorphisms （SNPs） that contribute to RA disease. The acquired SNP pairs were used to construct a SNP-SNP network. Sub-networks defined by hub SNPs were then extracted and turned into gene modules by mapping SNPs to genes using dbSNP database. We per- formed Gene Ontology （GO） analysis on each gene module, and some GO terms enriched in the gene modules can be used to investigate clustered gene function for better understanding RA pathogenesis. This method was applied to the Genetic Analysis Workshop 15 （GAW 15） RA dataset. The results show that genes involved in func- tional gene modules, such as CD160 （rs744877） and RUNX1 （rs2051179）, are especially relevant to RA, which is supported by previous reports. Furthermore, the 43 SNPs involved in the identified gene modules were found to be the best classifiers when used as variables for sample classification.

Delay-Distance Correlation Study for IP Geolocation

Although many classical IP geolocation algorithms are suitable to rich-connected networks, their performances are seriously affected in poor-connected networks with weak delay-distance correlation. This paper tries to improve the performances of classical IP geolocation algorithms by finding rich-connected sub-networks inside poor-connected networks. First, a new delay-distance correlation model （RTD-Corr model） is proposed. It builds the relationship between delay-distance correlation and actual network factors such as the tortuosity of the network path and the ratio of propagation delay. Second, based on the RTD-Corr model and actual network characteristics, this paper discusses about how to find rich-connected networks inside China Intemet which is a typical actual poor-connected network. Then we find rich-connected sub-networks of China Intemet through a large-scale network measurement which covers three major ISPs and thirty provinces. At last, based on the founded rich-connected sub-networks, we modify two classical IP geolocation algorithms and the experiments in China Intemet show that their accuracy is significantly increased.

Computational Identification of Protein-Protein Interactions in Rice Based on the Predicted Rice Interactome Network

Plant protein-protein interaction networks have not been identified by large-scale experiments. In order to better understand the protein interactions in rice, the Predicted Rice Interactome Network （PRIN; http：//bis.zju.edu.cn/ prin/） presented 76,585 predicted interactions involving 5,049 rice proteins. After mapping genomic features of rice （GO annotation, subcellular localizationprediction, and gene expression）, we found that a well-annotated and biologically significant network is rich enough to capture many significant functional linkages within higher-order biological systems, such as pathways and biological processes. Furthermore, we took MADS-box do- main-containing proteins and circadian rhythm signaling pathways as examples to demonstrate that functional protein complexes and biological pathways could be effectively expanded in our predicted network. The expanded molecular network in PRIN has considerably improved the capability of these analyses to integrate existing knowledge and provide novel insights into the function and coordination of genes and gene networks.