Huai Li

Bio: Huai Li is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Dependency network & Biological network. The author has an hindex of 13, co-authored 20 publications receiving 837 citations. Previous affiliations of Huai Li include Georgetown University Medical Center & The Catholic University of America.

Differential dependency network analysis to identify condition-specific topological changes in biological networks

Abstract: Motivation: Significant efforts have been made to acquire data under different conditions and to construct static networks that can explain various gene regulation mechanisms. However, gene regulatory networks are dynamic and condition-specific; under different conditions, networks exhibit different regulation patterns accompanied by different transcriptional network topologies. Thus, an investigation on the topological changes in transcriptional networks can facilitate the understanding of cell development or provide novel insights into the pathophysiology of certain diseases, and help identify the key genetic players that could serve as biomarkers or drug targets. Results: Here, we report a differential dependency network (DDN) analysis to detect statistically significant topological changes in the transcriptional networks between two biological conditions. We propose a local dependency model to represent the local structures of a network by a set of conditional probabilities. We develop an efficient learning algorithm to learn the local dependency model using the Lasso technique. A permutation test is subsequently performed to estimate the statistical significance of each learned local structure. In testing on a simulation dataset, the proposed algorithm accurately detected all the genes with network topological changes. The method was then applied to the estrogen-dependent T-47D estrogen receptor-positive (ER+) breast cancer cell line datasets and human and mouse embryonic stem cell datasets. In both experiments using real microarray datasets, the proposed method produced biologically meaningful results. We expect DDN to emerge as an important bioinformatics tool in transcriptional network analyses. While we focus specifically on transcriptional networks, the DDN method we introduce here is generally applicable to other biological networks with similar characteristics. Availability: The DDN MATLAB toolbox and experiment data are available at http://www.cbil.ece.vt.edu/software.htm. Contact: yuewang@vt.edu Supplementary information:Supplementary data are available at Bioinformatics online.

A multiple circular path convolution neural network system for detection of mammographic masses

Abstract: A multiple circular path convolution neural network (MCPCNN) architecture specifically designed for the analysis of tumor and tumor-like structures has been constructed. We first divided each suspected tumor area into sectors and computed the defined mass features for each sector independently. These sector features were used on the input layer and were coordinated by convolution kernels of different sizes that propagated signals to the second layer in the neural network system. The convolution kernels were trained, as required, by presenting the training cases to the neural network. In this study, randomly selected mammograms were processed by a dual morphological enhancement technique. Radiodense areas were isolated and were delineated using a region growing algorithm. The boundary of each region of interest was then divided into 36 sectors using 36 equi-angular dividers radiated from the center of the region. A total of 144 Breast Imaging-Reporting and Data System-based features (i.e., four features per sector for 36 sectors) were computed as input values for the evaluation of this newly invented neural network system. The overall performance was 0.78-0.80 for the areas (A/sub z/) under the receiver operating characteristic curves using the conventional feed-forward neural network in the detection of mammographic masses. The performance was markedly improved with A/sub z/ values ranging from 0.84 to 0.89 using the MCPCNN. This paper does not intend to claim the best mass detection system. Instead it reports a potentially better neural network structure for analyzing a set of the mass features defined by an investigator.

Optimization of wavelet decomposition for image compression and feature preservation

Abstract: A neural-network-based framework has been developed to search for an optimal wavelet kernel that can be used for a specific image processing task. In this paper, a linear convolution neural network was employed to seek a wavelet that minimizes errors and maximizes compression efficiency for an image or a defined image pattern such as microcalcifications in mammograms and bone in computed tomography (CT) head images. We have used this method to evaluate the performance of tap-4 wavelets on mammograms, CTs, magnetic resonance images, and Lena images. We found that the Daubechies wavelet or those wavelets with similar filtering characteristics can produce the highest compression efficiency with the smallest mean-square-error for many image patterns including general image textures as well as microcalcifications in digital mammograms. However, the Haar wavelet produces the best results on sharp edges and low-noise smooth areas. We also found that a special wavelet (whose low-pass filter coefficients are 0.32252136, 0.85258927, 0.38458542, and -0.14548269) produces the best preservation outcomes in all tested microcalcification features including the peak signal-to-noise ratio, the contrast and the figure of merit in the wavelet lossy compression scheme. Having analyzed the spectrum of the wavelet filters, we can find the compression outcomes and feature preservation characteristics as a function of wavelets. This newly developed optimization approach can be generalized to other image analysis applications where a wavelet decomposition is employed.

Inferring regulatory networks.

Abstract: The discovery of regulatory networks is an important aspect in the post genomic research. The process requires integrated efforts of experimental and computational strategies by employing the systems biology approach. This review summarizes some of the major themes in computational inference of regulatory networks based on gene expression and other data sources, including transcriptional module identification, network topology inference, and network analysis. Popular solutions to each of these problems and their relative merits are discussed.

Singular Value Decomposition for Genome-Wide Expression Data Processing and Modeling

Abstract: ‡We describe the use of singular value decomposition in transforming genome-wide expression data from genes 3 arrays space to reduced diagonalized ‘‘eigengenes’’ 3 ‘‘eigenarrays’’ space, where the eigengenes (or eigenarrays) are unique orthonormal superpositions of the genes (or arrays). Normalizing the data by filtering out the eigengenes (and eigenarrays) that are inferred to represent noise or experimental artifacts enables meaningful comparison of the expression of different genes across different arrays in different experiments. Sorting the data according to the eigengenes and eigenarrays gives a global picture of the dynamics of gene expression, in which individual genes and arrays appear to be classified into groups of similar regulation and function, or similar cellular state and biological phenotype, respectively. After normalization and sorting, the significant eigengenes and eigenarrays can be associated with observed genome-wide effects of regulators, or with measured samples, in which these regulators are overactive or underactive, respectively.

Pulmonary Nodule Detection in CT Images: False Positive Reduction Using Multi-View Convolutional Networks

Abstract: We propose a novel Computer-Aided Detection (CAD) system for pulmonary nodules using multi-view convolutional networks (ConvNets), for which discriminative features are automatically learnt from the training data. The network is fed with nodule candidates obtained by combining three candidate detectors specifically designed for solid, subsolid, and large nodules. For each candidate, a set of 2-D patches from differently oriented planes is extracted. The proposed architecture comprises multiple streams of 2-D ConvNets, for which the outputs are combined using a dedicated fusion method to get the final classification. Data augmentation and dropout are applied to avoid overfitting. On 888 scans of the publicly available LIDC-IDRI dataset, our method reaches high detection sensitivities of 85.4% and 90.1% at 1 and 4 false positives per scan, respectively. An additional evaluation on independent datasets from the ANODE09 challenge and DLCST is performed. We showed that the proposed multi-view ConvNets is highly suited to be used for false positive reduction of a CAD system.