arXiv subjects

Xizhe Zhang

Publications and source records attributed to Xizhe Zhang.

29 records · Page 2Linked to original sources

arXiv2023

NetMoST: A network-based machine learning approach for subtyping schizophrenia using polygenic SNP allele biomarkers

Subtyping neuropsychiatric disorders like schizophrenia is essential for improving the diagnosis and treatment of complex diseases. Subtyping schizophrenia is challenging because it is polygenic and genetically heterogeneous, rendering the standard symptom-based diagnosis often unreliable and unrepeatable. We developed a novel network-based machine-learning approach, netMoST, to subtyping psychiatric disorders. NetMoST identifies polygenic risk SNP-allele modules from genome-wide genotyping data as polygenic haplotype biomarkers (PHBs) for disease subtyping. We applied netMoST to subtype a cohort of schizophrenia subjects into three distinct biotypes with differentiable genetic, neuroimaging and functional characteristics. The PHBs of the first biotype (36.9% of all patients) were related to neurodevelopment and cognition, the PHBs of the second biotype (28.4%) were enriched for neuroimmune functions, and the PHBs of the third biotype (34.7%) were associated with the transport of calcium ions and neurotransmitters. Neuroimaging patterns provided additional support to the new biotypes, with unique regional homogeneity (ReHo) patterns observed in the brains of each biotype compared with healthy controls. Our findings demonstrated netMoST's capability for uncovering novel biotypes of complex diseases such as schizophrenia. The results also showed the power of exploring polygenic allelic patterns that transcend the conventional GWAS approaches.

q-bio.MN↗

arXiv2022

Identification of cancer-keeping genes as therapeutic targets by finding network control hubs

Finding cancer driver genes has been a focal theme of cancer research and clinical studies. One of the recent approaches is based on network structural controllability that focuses on finding a control scheme and driver genes that can steer the cell from an arbitrary state to a designated state. While theoretically sound, this approach is impractical for many reasons, e.g., the control scheme is often not unique and half of the nodes may be driver genes for the cell. We developed a novel approach that transcends structural controllability. Instead of considering driver genes for one control scheme, we considered control hub genes that reside in the middle of a control path of every control scheme. Control hubs are the most vulnerable spots for controlling the cell and exogenous stimuli on them may render the cell uncontrollable. We adopted control hubs as cancer-keep genes (CKGs) and applied them to a gene regulatory network of bladder cancer (BLCA). All the genes on the cell cycle and p53 singling pathways in BLCA are CKGs, confirming the importance of these genes and the two pathways in cancer. A smaller set of 35 sensitive CKGs (sCKGs) for BLCA was identified by removing network links. Six sCKGs (RPS6KA3, FGFR3, N-cadherin (CDH2), EP300, caspase-1, and FN1) were subjected to small-interferencing-RNA knockdown in four cell lines to validate their effects on the proliferation or migration of cancer cells. Knocking down RPS6KA3 in a mouse model of BLCA significantly inhibited the growth of tumor xenografts in the mouse model. Combined, our results demonstrated the value of CKGs as therapeutic targets for cancer therapy and the potential of CKGs as an effective means for studying and characterizing cancer etiology.

q-bio.MN↗

arXiv2022

Response to: Significance and stability of deep learning-based identification of subtypes within major psychiatric disorders. Molecular Psychiatry (2022)

Recently, Winter and Hahn [1] commented on our work on identifying subtypes of major psychiatry disorders (MPDs) based on neurobiological features using machine learning [2]. They questioned the generalizability of our methods and the statistical significance, stability, and overfitting of the results, and proposed a pipeline for disease subtyping. We appreciate their earnest consideration of our work, however, we need to point out their misconceptions of basic machine-learning concepts and delineate some key issues involved.

cs.LG↗

arXiv2022

Control hubs of complex networks and a polynomial-time identification algorithm

Unveiling the underlying control principles of complex networks is one of the ultimate goals of network science. We introduce a novel concept, control hub, to reveal a cornerstone of the control structure of a network. The control hubs of a network are the nodes that lie in the middle of a control path in every control scheme of the network. We present a theorem based on graph theory for identifying control hubs without computing all control schemes. We develop an algorithm to identify all control hubs in O(N0.5L) time complexity for a network of N nodes and L links.

cs.DM↗

arXiv2019

Altering control modes of complex networks based on edge removal

Controlling a complex network is of great importance in many applications. The network can be controlled by inputting external control signals through some selected nodes, which are called input nodes. Previous works found that the majority of the nodes in dense networks are either the input nodes or not, which leads to the bimodality in controlling the complex networks. Due to the physical or economic constraints of many real control scenarios, altering the control mode of a network may be critical to many applications. Here we develop a graph-based algorithm to alter the control mode of a network. The main idea is to change the control connectivity of nodes by removing carefully selected edges. We rigorously prove the correctness of our algorithm and evaluate its performance on both synthetic and real networks. The experimental results show that the control mode of a network can be easily changed by removing few selected edges. Our methods provide the ability to design the desired control mode for different control scenarios, which may be useful in many applications.

cs.SI↗

arXiv2019

Altering nodes types in controlling complex networks

Controlling a complex network towards a desired state is of great importance in many applications. A network can be controlled by inputting suitable external signals into some selected nodes, which are called driver nodes. Previous works found there exist two control modes in dense networks: distributed and centralized modes. For networks with the distributed mode, most of the nodes can be act as driver nodes; and those with the centralized mode, most of the nodes never be the driver nodes. Here we present an efficient algorithm to change the control type of nodes, from input nodes to redundant nodes, which is done by reversing edges of the network. We conclude four possible cases when reversing an edge and show the control mode can be changed by reversing very few in-edges of driver nodes. We evaluate the performance of our algorithm on both synthetic and real networks. The experimental results show that the control mode of a network can be easily changed by reversing a few elaborately selected edges, and the number of possible driver nodes is dramatically decreased. Our methods provide the ability to design the desired control modes of the network for different control scenarios, which may be used in many application regions.

eess.SY↗

arXiv2017

An efficient algorithm for finding all possible input nodes for controlling complex networks

Understanding structural controllability of a complex network requires to identify a Minimum Input nodes Set (MIS) of the network. It has been suggested that finding an MIS is equivalent to computing a maximum matching of the network, where the unmatched nodes constitute an MIS. However, maximum matching of a network is often not unique, and finding all MISs may provide deep insights to the controllability of the network. Finding all possible input nodes, which form the union of all MISs, is computationally challenging for large networks. Here we present an efficient enumerative algorithm for the problem. The main idea is to modify a maximum matching algorithm to make it efficient for finding all possible input nodes by computing only one MIS. We rigorously proved the correctness of the new algorithm and evaluated its performance on synthetic and large real networks. The experimental results showed that the new algorithm ran several orders of magnitude faster than the existing method on large real networks.

cs.DM↗

arXiv2016

Input graph: the hidden geometry in controlling complex networks

The ability to control a complex network towards a desired behavior relies on our understanding of the complex nature of these social and technological networks. The existence of numerous control schemes in a network promotes us to wonder: what is the underlying relationship of all possible input nodes? Here we introduce input graph, a simple geometry that reveals the complex relationship between all control schemes and input nodes. We prove that the node adjacent to an input node in the input graph will appear in another control scheme, and the connected nodes in input graph have the same type in control, which they are either all possible input nodes or not. Furthermore, we find that the giant components emerge in the input graphs of many real networks, which provides a clear topological explanation of bifurcation phenomenon emerging in dense networks and promotes us to design an efficient method to alter the node type in control. The findings provide an insight into control principles of complex networks and offer a general mechanism to design a suitable control scheme for different purposes.

eess.SY↗

arXiv2016

Robustness of indispensable nodes in controlling protein-protein interaction network

Recently, the structural controllability theory has been introduced to analyze the Protein-Protein Interaction (PPI) network. The indispensable nodes, which their removal increase the number of driver nodes to control the network, are found essential in PPI network. However, the PPI network is far from complete and there may exist many false-positive or false-negative interactions, which promotes us to question: are these indispensable nodes robust to structural change? Here we systematically investigate the robustness of indispensable nodes of PPI network by removing and adding possible interactions. We found that the indispensable nodes are sensitive to the structural change and very few edges can change the type of many indispensable nodes. The finding may promote our understanding to the control principle of PPI network.

physics.comp-ph↗

arXiv2016

Efficient target control of complex networks based on preferential matching

Controlling a complex network towards a desire state is of great importance in many applications. Existing works present an approximate algorithm to find the driver nodes used to control partial nodes of the network. However, the driver nodes obtained by this algorithm depend on the matching order of nodes and cannot get the optimum results. Here we present a novel algorithm to find the driver nodes for target control based on preferential matching. The algorithm elaborately arrange the matching order of nodes in order to minimize the size of the driver nodes set. The results on both synthetic and real networks indicate that the performance of proposed algorithm are better than the previous one. The algorithm may have various application in controlling complex networks.

physics.soc-ph↗

arXiv2014

Structure controllability of complex network based on preferential matching

Minimum driver node sets (MDSs) play an important role in studying the structural controllability of complex networks. Recent research has shown that MDSs tend to avoid high-degree nodes. However, this observation is based on the analysis of a small number of MDSs, because enumerating all of the MDSs of a network is a #P problem. Therefore, past research has not been sufficient to arrive at a convincing conclusion. In this paper, first, we propose a preferential matching algorithm to find MDSs that have a specific degree property. Then, we show that the MDSs obtained by preferential matching can be composed of high- and medium-degree nodes. Moreover, the experimental results also show that the average degree of the MDSs of some networks tends to be greater than that of the overall network, even when the MDSs are obtained using previous research method. Further analysis shows that whether the driver nodes tend to be high-degree nodes or not is closely related to the edge direction of the network.

math-ph↗