arXiv subjects

Ling-Yun Wu

Publications and source records attributed to Ling-Yun Wu.

6 recordsLinked to original sources

arXiv2026

HyperNetWalk: A Unified Framework for Personalized and Cohort-Level Cancer Driver Gene Identification via Reverse Inference on Layered Signaling-Regulatory Network

Accurate identification of cancer driver genes from passenger mutations is essential for understanding tumorigenesis and clinical translation. We present HyperNetWalk, an unsupervised framework that unifies personalized and cohort-level driver gene identification within a shared inference architecture. HyperNetWalk builds a layered signaling-regulatory network by integrating protein-protein interactions, approximating upstream signaling, with a gene regulatory network for downstream transcriptional regulation, with transcription factors serving as interface nodes. Driver identification is formulated as an inverse problem in which observed transcriptional dysregulation is traced back to candidate upstream drivers by reverse random walk. The resulting sample-specific scores are used directly for personalized prediction and as node weights for cross-sample refinement through hypergraph random walk, enabling both local personalized and global cohort-level prediction. Across 12 TCGA cancer types, HyperNetWalk outperformed representative existing methods at both prediction levels. Ablation analyses supported the contributions of the reverse inference formulation and layered network architecture. Further analyses showed that HyperNetWalk captured cancer-type-specific driver signals, prioritized both recurrent and low-frequency candidate drivers, and produced predictions supported by drug-gene interaction and clinical actionability annotations.

q-bio.QM↗

arXiv2021

Understanding the network formation pattern for better link prediction

As a classical problem in the field of complex networks, link prediction has attracted much attention from researchers, which is of great significance to help us understand the evolution and dynamic development mechanisms of networks. Although various network type-specific algorithms have been proposed to tackle the link prediction problem, most of them suppose that the network structure is dominated by the Triadic Closure Principle. We still lack an adaptive and comprehensive understanding of network formation patterns for predicting potential links. In addition, it is valuable to investigate how network local information can be better utilized. To this end, we proposed a novel method named Link prediction using Multiple Order Local Information (MOLI) that exploits the local information from the neighbors of different distances, with parameters that can be a prior-driven based on prior knowledge, or data-driven by solving an optimization problem on observed networks. MOLI defined a local network diffusion process via random walks on the graph, resulting in better use of network information. We show that MOLI outperforms the other 11 widely used link prediction algorithms on 11 different types of simulated and real-world networks. We also conclude that there are different patterns of local information utilization for different networks, including social networks, communication networks, biological networks, etc. In particular, the classical common neighbor-based algorithm is not as adaptable to all social networks as it is perceived to be; instead, some of the social networks obey the Quadrilateral Closure Principle which preferentially connects paths of length three.

physics.soc-ph↗

arXiv2021

Network Refinement: A unified framework for enhancing signal or removing noise of networks

Networks are widely used in many fields for their powerful ability to provide vivid representations of relationships between variables. However, many of them may be corrupted by experimental noise or inappropriate network inference methods that inherently hamper the efficacy of network-based downstream analysis. Consequently, it's necessary to develop systematic methods for denoising networks, namely, improve the Signal-to-Noise Ratio (SNR) of noisy networks. In this paper, we have explored the properties of network signal and noise and proposed a novel network denoising framework called Network Refinement (NR) that adjusts the edge weights by applying a nonlinear graph operator based on a diffusion process defined by random walk on the graph. Specifically, this unified framework consists of two closely linked approaches named NR-F and NR-B, which improve the SNR of noisy input networks from two different perspectives: NR-F aims at enhancing signal strength, while NR-B aims at weakening noise strength. Users can choose from which angle to improve the SNR of the network according to the characteristics of the network itself. We show that NR can significantly refine the quality of many networks by several applications on simulated networks and typical real-world biological and social networks.

q-bio.MN↗

arXiv2015

Potts model based on a Markov process computation solves the community structure problem effectively

Potts model is a powerful tool to uncover community structure in complex networks. Here, we propose a new framework to reveal the optimal number of communities and stability of network structure by quantitatively analyzing the dynamics of Potts model. Specifically we model the community structure detection Potts procedure by a Markov process, which has a clear mathematical explanation. Then we show that the local uniform behavior of spin values across multiple timescales in the representation of the Markov variables could naturally reveal the network's hierarchical community structure. In addition, critical topological information regarding to multivariate spin configuration could also be inferred from the spectral signatures of the Markov process. Finally an algorithm is developed to determine fuzzy communities based on the optimal number of communities and the stability across multiple timescales. The effectiveness and efficiency of our algorithm are theoretically analyzed as well as experimentally validated.

physics.soc-ph↗

arXiv2014

Cancer stem cells display extremely large evolvability: alternating plastic and rigid networks as a potential mechanism

Cancer is increasingly perceived as a systems-level, network phenomenon. The major trend of malignant transformation can be described as a two-phase process, where an initial increase of network plasticity is followed by a decrease of plasticity at late stages of tumor development. The fluctuating intensity of stress factors, like hypoxia, inflammation and the either cooperative or hostile interactions of tumor inter-cellular networks, all increase the adaptation potential of cancer cells. This may lead to the bypass of cellular senescence, and to the development of cancer stem cells. We propose that the central tenet of cancer stem cell definition lies exactly in the indefinability of cancer stem cells. Actual properties of cancer stem cells depend on the individual "stress-history" of the given tumor. Cancer stem cells are characterized by an extremely large evolvability (i.e. a capacity to generate heritable phenotypic variation), which corresponds well with the defining hallmarks of cancer stem cells: the possession of the capacity to self-renew and to repeatedly re-build the heterogeneous lineages of cancer cells that comprise a tumor in new environments. Cancer stem cells represent a cell population, which is adapted to adapt. We argue that the high evolvability of cancer stem cells is helped by their repeated transitions between plastic (proliferative, symmetrically dividing) and rigid (quiescent, asymmetrically dividing, often more invasive) phenotypes having plastic and rigid networks. Thus, cancer stem cells reverse and replay cancer development multiple times. We describe network models potentially explaining cancer stem cell-like behavior. Finally, we propose novel strategies including combination therapies and multi-target drugs to overcome the Nietzschean dilemma of cancer stem cell targeting: "what does not kill me makes me stronger".

q-bio.MN↗

arXiv2013

Structure and dynamics of core-periphery networks

Recent studies uncovered important core/periphery network structures characterizing complex sets of cooperative and competitive interactions between network nodes, be they proteins, cells, species or humans. Better characterization of the structure, dynamics and function of core/periphery networks is a key step of our understanding cellular functions, species adaptation, social and market changes. Here we summarize the current knowledge of the structure and dynamics of "traditional" core/periphery networks, rich-clubs, nested, bow-tie and onion networks. Comparing core/periphery structures with network modules, we discriminate between global and local cores. The core/periphery network organization lies in the middle of several extreme properties, such as random/condensed structures, clique/star configurations, network symmetry/asymmetry, network assortativity/disassortativity, as well as network hierarchy/anti-hierarchy. These properties of high complexity together with the large degeneracy of core pathways ensuring cooperation and providing multiple options of network flow re-channelling greatly contribute to the high robustness of complex systems. Core processes enable a coordinated response to various stimuli, decrease noise, and evolve slowly. The integrative function of network cores is an important step in the development of a large variety of complex organisms and organizations. In addition to these important features and several decades of research interest, studies on core/periphery networks still have a number of unexplored areas.

physics.soc-ph↗