The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Luonan Chen's research lab specializes in computational systems biology and bioinformatics, focusing on modeling complex biological systems, particularly gene regulatory networks and molecular networks in disease progression. The lab develops advanced computational methods to infer individual-specific and single-cell resolution networks from high-throughput 'omics' data, enabling the detection of early-warning signals for critical transitions in complex diseases. Key research directions include the inference of dynamic, condition-specific networks, the identification of dynamical network biomarkers, and the construction of integrative knowledge bases for virulence factors in pathogens. The lab emphasizes methodological innovation to address challenges such as small sample sizes, network heterogeneity, and the distinction between direct and indirect regulatory interactions.
Figures are computed from collected data and may differ slightly.
Considerable evidence suggests that during the progression of complex diseases, the deteriorations are not necessarily smooth but are abrupt, and may cause a critical transition from one state to another at a tipping point. Here, we develop a model-free method to detect early-warning signals of such critical transitions, even with only a small number of samples. Specifically, we theoretically derive an index based on a dynamical network biomarker (DNB) that serves as a general early-warning sign
A complex disease generally results not from malfunction of individual molecules but from dysfunction of the relevant system or network, which dynamically changes with time and conditions. Thus, estimating a condition-specific network from a single sample is crucial to elucidating the molecular mechanisms of complex diseases at the system level. However, there is currently no effective way to construct such an individual-specific network by expression profiling of a single sample because of the
Single-cell RNA sequencing (scRNA-seq) is able to give an insight into the gene-gene associations or transcriptional networks among cell populations based on the sequencing of a large number of cells. However, traditional network methods are limited to the grouped cells instead of each single cell, and thus the heterogeneity of single cells will be erased. We present a new method to construct a cell-specific network (CSN) for each single cell from scRNA-seq data (i.e. one network for one cell),
Virulence factors (VFs) are molecules that allow microbial pathogens to overcome host defense mechanisms and cause disease in a host. It is critical to study VFs for better understanding microbial pathogenesis and host defense mechanisms. Victors (http://www.phidias.us/victors) is a novel, manually curated, web-based integrative knowledge base and analysis resource for VFs of pathogens that cause infectious diseases in human and animals. Currently, Victors contains 5296 VFs obtained via manual a
The inference of gene regulatory networks (GRNs) from expression data can mine the direct regulations among genes and gain deep insights into biological processes at a network level. During past decades, numerous computational approaches have been introduced for inferring the GRNs. However, many of them still suffer from various problems, e.g., Bayesian network (BN) methods cannot handle large-scale networks due to their high computational complexity, while information theory-based methods canno
Mutual information (MI), a quantity describing the nonlinear dependence between two random variables, has been widely used to construct gene regulatory networks (GRNs). Despite its good performance, MI cannot separate the direct regulations from indirect ones among genes. Although the conditional mutual information (CMI) is able to identify the direct regulations, it generally underestimates the regulation strength, i.e. it may result in false negatives when inferring gene regulations. In this w
Network-based computational biology, with the emphasis on biomolecular interactions and omics-data integration, has had success in drug development and created new directions such as drug repositioning and drug combination. Drug repositioning, i.e., revealing a drug's new roles, is increasingly attracting much attention from the pharmaceutical community to tackle the problems of high failure rate and long-term development in drug discovery. While drug combination or drug cocktails, i.e., combini
Supplementary data are available at Bioinformatics online.
All the source data and code are available at: http://csb.shu.edu.cn/narromi.htm.
Simultaneous profiling transcriptomic and chromatin accessibility information in the same individual cells offers an unprecedented resolution to understand cell states. However, computationally effective methods for the integration of these inherent sparse and heterogeneous data are lacking. Here, we present a single-cell multimodal variational autoencoder model, which combines three types of joint-learning strategies with a probabilistic Gaussian Mixture Model to learn the joint latent features
Generally, protein classification is a multi-class classification problem and can be reduced to a set of binary classification problems, where one classifier is designed for each class. The proteins in one class are seen as positive examples while those outside the class are seen as negative examples. However, the imbalanced problem will arise in this case because the number of proteins in one class is usually much smaller than that of the proteins outside the class. As a result, the imbalanced
This paper aims to theoretically prove that both transiently chaotic neural networks (TCNN's) and discrete-time recurrent neural networks (DRNN's) have a global attracting set which ensures that the neural networks carry out a global search. A significant property of TCNN's and DRNN's is that their attracting sets are generated by a bounded fixed point, which is the unique repeller when absolute values of the self-feedback connection weights in TCNN and the difference time in DRNN are sufficient
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