DReSS: a method to quantitatively describe the influence of structural perturbations on state spaces of genetic regulatory networks.

Structures of genetic regulatory networks are not fixed. These structural perturbations can cause changes to the reachability of systems' state spaces. As system structures are related to genotypes and state spaces are related to phenotypes, it is important to study the relationship between structures and state spaces. However, there is still no method can quantitively describe the reachability differences of two state spaces caused by structural perturbations. Therefore, Difference in Reachability between State Spaces (DReSS) is proposed. DReSS index family can quantitively describe differences of reachability, attractor sets between two state spaces and can help find the key structure in a system, which may influence system's state space significantly. First, basic properties of DReSS including non-negativity, symmetry and subadditivity are proved. Then, typical examples are shown to explain the meaning of DReSS and the differences between DReSS and traditional graph distance. Finally, differences of DReSS distribution between real biological regulatory networks and random networks are compared. Results show most structural perturbations in biological networks tend to affect reachability inside and between attractor basins rather than to affect attractor set itself when compared with random networks, which illustrates that most genotype differences tend to influence the proportion of different phenotypes and only a few ones can create new phenotypes. DReSS can provide researchers with a new insight to study the relation between genotypes and phenotypes.

LAMP: disease classification derived from layered assessment on modules and pathways in the human gene network.

BACKGROUND: Classification of diseases based on genetic information is of great significance as the basis for precision medicine, increasing the understanding of disease etiology and revolutionizing personalized medicine. Much effort has been directed at understanding disease associations by constructing disease networks, and classifying patient samples according to gene expression data. Integrating human gene networks overcomes limited coverage of genes. Incorporating pathway information into disease classification procedure addresses the challenge of cellular heterogeneity across patients. RESULTS: In this work, we propose a disease classification model LAMP, which concentrates on the layered assessment on modules and pathways. Directed human gene interactions are the foundation of constructing the human gene network, where the significant roles of disease and pathway genes are recognized. The fast unfolding algorithm identifies 11 modules in the largest connected component. Then layered networks are introduced to distinguish positions of genes in propagating information from sources to targets. After gene screening, hierarchical clustering and refined process, 1726 diseases from KEGG are classified into 18 categories. Also, it is expounded that diseases with overlapping genes may not belong to the same category in LAMP. Within each category, entropy is applied to measure the compositional complexity, and to evaluate the prospects for combination diagnosis and gene-targeted therapy for diseases. CONCLUSION: In this work, by collecting data from BioGRID and KEGG, we develop a disease classification model LAMP, to support people to view diseases from the perspective of commonalities in etiology and pathology. Comprehensive research on existing diseases can help meet the challenges of unknown diseases. The results provide suggestions for combination diagnosis and gene-targeted therapy, which motivates clinicians and researchers to reposition the understanding of diseases and explore diagnosis and therapy strategies.

Cross-modal semantic autoencoder with embedding consensus.

Cross-modal retrieval has become a topic of popularity, since multi-data is heterogeneous and the similarities between different forms of information are worthy of attention. Traditional single-modal methods reconstruct the original information and lack of considering the semantic similarity between different data. In this work, a cross-modal semantic autoencoder with embedding consensus (CSAEC) is proposed, mapping the original data to a low-dimensional shared space to retain semantic information. Considering the similarity between the modalities, an automatic encoder is utilized to associate the feature projection to the semantic code vector. In addition, regularization and sparse constraints are applied to low-dimensional matrices to balance reconstruction errors. The high dimensional data is transformed into semantic code vector. Different models are constrained by parameters to achieve denoising. The experiments on four multi-modal data sets show that the query results are improved and effective cross-modal retrieval is achieved. Further, CSAEC can also be applied to fields related to computer and network such as deep and subspace learning. The model breaks through the obstacles in traditional methods, using deep learning methods innovatively to convert multi-modal data into abstract expression, which can get better accuracy and achieve better results in recognition.

Gene Saturation: An Approach to Assess Exploration Stage of Gene Interaction Networks.

The gene interaction network is one of the most important biological networks and has been studied by many researchers. The gene interaction network provides information about whether the genes in the network can cause or heal diseases. As gene-gene interaction relations are constantly explored, gene interaction networks are evolving. To describe how much a gene has been studied, an approach based on a logistic model for each gene called gene saturation has been proposed, which in most cases, satisfies non-decreasing, correlation and robustness principles. The average saturation of a group of genes can be used to assess the network constructed by these genes. Saturation reflects the distance between known gene interaction networks and the real gene interaction network in a cell. Furthermore, the saturation values of 546 disease gene networks that belong to 15 categories of diseases have been calculated. The disease gene networks' saturation for cancer is significantly higher than that of all other diseases, which means that the disease gene networks' structure for cancer has been more deeply studied than other disease. Gene saturation provides guidance for selecting an experimental subject gene, which may have a large number of unknown interactions.

Disease classification via gene network integrating modules and pathways.

Disease classification based on gene information has been of significance as the foundation for achieving precision medicine. Previous works focus on classifying diseases according to the gene expression data of patient samples, and constructing disease network based on the overlap of disease genes, as many genes have been confirmed to be associated with diseases. In this work, the effects of diseases on human biological functions are assessed from the perspective of gene network modules and pathways, and the distances between diseases are defined to carry out the classification models. In total, 1728 diseases are divided into 12 and 14 categories by the intensity and scope of effects on pathways, respectively. Each category is a mix of several types of diseases identified based on congenital and acquired factors as well as diseased tissues and organs. The disease classification models on the basis of gene network are parallel with traditional pathology classification based on anatomic and clinical manifestations, and enable us to look at diseases in the viewpoint of commonalities in etiology and pathology. Our models provide a foundation for exploring combination therapy of diseases, which in turn may inform strategies for future gene-targeted therapy.