MOTIVATION: Cell function is regulated by gene regulatory networks (GRNs) defined by protein-mediated interaction between constituent genes. Despite advances in experimental techniques, we can still measure only a fraction of the processes that govern GRN dynamics. To infer the properties of GRNs using partial observation, unobserved sequential processes can be replaced with distributed time delays, yielding non-Markovian models. Inference methods based on the resulting model suffer from the curse of dimensionality. RESULTS: We develop a simulation-based Bayesian MCMC method employing an approximate likelihood for the efficient and accurate inference of GRN parameters when only some of their products are observed. We illustrate our approach using a two-step activation model: an activation signal leads to the accumulation of an unobserved regulatory protein, which triggers the expression of observed fluorescent proteins. With prior information about observed fluorescent protein synthesis, our method successfully infers the dynamics of the unobserved regulatory protein. We can estimate the delay and kinetic parameters characterizing target regulation including transcription, translation, and target searching of an unobserved protein from experimental measurements of the products of its target gene. Our method is scalable and can be used to analyze non-Markovian models with hidden components. AVAILABILITY AND IMPLEMENTATION: Our code is implemented in R and is freely available with a simple example data at https://github.com/Mathbiomed/SimMCMC.

MOTIVATION: In spite of great success of genome-wide association studies (GWAS), multiple challenges still remain. First, complex traits are often associated with many single nucleotide polymorphisms (SNPs), each with small or moderate effect sizes. Second, our understanding of the functional mechanisms through which genetic variants are associated with complex traits is still limited. To address these challenges, we propose GPA-Tree and it simultaneously implements association mapping and identifies key combinations of functional annotations related to risk-associated SNPs by combining a decision tree algorithm with a hierarchical modeling framework. RESULTS: First, we implemented simulation studies to evaluate the proposed GPA-Tree method and compared its performance with existing statistical approaches. The results indicate that GPA-Tree outperforms existing statistical approaches in detecting risk-associated SNPs and identifying the true combinations of functional annotations with high accuracy. Second, we applied GPA-Tree to a systemic lupus erythematosus (SLE) GWAS and functional annotation data including GenoSkyline and GenoSkylinePlus. The results from GPA-Tree highlight the dysregulation of blood immune cells, including but not limited to primary B, memory helper T, regulatory T, neutrophils and CD8+ memory T cells in SLE. These results demonstrate that GPA-Tree can be a powerful tool that improves association mapping while facilitating understanding of the underlying genetic architecture of complex traits and potential mechanisms linking risk-associated SNPs with complex traits. AVAILABILITY AND IMPLEMENTATION: The GPATree software is available at https://dongjunchung.github.io/GPATree/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Summary: Integration of genetic studies for multiple phenotypes is a powerful approach to improving the identification of genetic variants associated with complex traits. Although it has been shown that leveraging shared genetic basis among phenotypes, namely pleiotropy, can increase statistical power to identify risk variants, it remains challenging to effectively integrate genome-wide association study (GWAS) datasets for a large number of phenotypes. We previously developed graph-GPA, a Bayesian hierarchical model that integrates multiple GWAS datasets to boost statistical power for the identification of risk variants and to estimate pleiotropic architecture within a unified framework. Here we propose a novel improvement of graph-GPA which incorporates external knowledge about phenotype-phenotype relationship to guide the estimation of genetic correlation and the association mapping. The application of graph-GPA to GWAS datasets for 12 complex diseases with a prior disease graph obtained from a text mining of biomedical literature illustrates its power to improve the identification of risk genetic variants and to facilitate understanding of genetic relationship among complex diseases. Availability and implementation: graph-GPA is implemented as an R package 'GGPA', which is publicly available at http://dongjunchung.github.io/GGPA/. DDNet, a web interface to query diseases of interest and download a prior disease graph obtained from a text mining of biomedical literature, is publicly available at http://www.chunglab.io/ddnet/. Supplementary information: Supplementary data are available at Bioinformatics online.

Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. However, identification of risk variants associated with complex diseases remains challenging as they are often affected by many genetic variants with small or moderate effects. There has been accumulating evidence suggesting that different complex traits share common risk basis, namely pleiotropy. Recently, several statistical methods have been developed to improve statistical power to identify risk variants for complex traits through a joint analysis of multiple GWAS datasets by leveraging pleiotropy. While these methods were shown to improve statistical power for association mapping compared to separate analyses, they are still limited in the number of phenotypes that can be integrated. In order to address this challenge, in this paper, we propose a novel statistical framework, graph-GPA, to integrate a large number of GWAS datasets for multiple phenotypes using a hidden Markov random field approach. Application of graph-GPA to a joint analysis of GWAS datasets for 12 phenotypes shows that graph-GPA improves statistical power to identify risk variants compared to statistical methods based on smaller number of GWAS datasets. In addition, graph-GPA also promotes better understanding of genetic mechanisms shared among phenotypes, which can potentially be useful for the development of improved diagnosis and therapeutics. The R implementation of graph-GPA is currently available at https://dongjunchung.github.io/GGPA/.

The current paper proposes a font classification method for document images that uses non-negative matrix factorization (NMF), that is able to learn part-based representations of objects. The basic idea of the proposed method is based on the fact that the characteristics of each font are derived from parts of individual characters in each font rather than holistic textures. Spatial localities, parts composing of font images, are automatically extracted using NMF and, then, used as features representing each font. Using hierarchical clustering algorithm, these feature sets are generalized for font classification, resulting in the prototype templates construction. In both the prototype construction and font classification, earth mover's distance (EMD) is used as the distance metric, which is more suitable for the NMF feature space than Cosine or Euclidean distance. In the experimental results, the distribution of features and the appropriateness of the features specifying each font are investigated, and the results are compared with a related algorithm: principal component analysis (PCA). The proposed method is expected to improve the performance of optical character recognition (OCR), document indexing and retrieval systems, when such systems adopt a font classifier as a preprocessor.

This paper investigates the application of support vector machines (SVMs) in texture classification. Instead of relying on an external feature extractor, the SVM receives the gray-level values of the raw pixels, as SVMs can generalize well even in high-dimensional spaces. Furthermore, it is shown that SVMs can incorporate conventional texture feature extraction methods within their own architecture, while also providing solutions to problems inherent in these methods. One-against-others decomposition is adopted to apply binary SVMs to multitexture classification, plus a neural network is used as an arbitrator to make final classifications from several one-against-others SVM outputs. Experimental results demonstrate the effectiveness of SVMs in texture classification.

A kernel principal component analysis (PCA) was previously proposed as a nonlinear extension of a PCA. The basic idea is to first map the input space into a feature space via nonlinear mapping and then compute the principal components in that feature space. This article adopts the kernel PCA as a mechanism for extracting facial features. Through adopting a polynomial kernel, the principal components can be computed within the space spanned by high-order correlations of input pixels making up a facial image, thereby producing a good performance.

To support the content-based functionalities in the new video coding standard MPEG-4, each frame of a video sequence must first be extracted into video object planes, each of which represents a meaningful moving object. However, extraction and tracking of a video sequence into video object planes remains a difficult and unresolved problem. Accordingly, this paper presents an object extraction and tracking method based on genetic algorithms that can automatically extract and track moving objects. Each frame is spatially segmented by chromosomes that evolve using distributed genetic algorithms. Thereafter, the spatial segmentation result is combined with a change detection mask, thereby creating the video object planes. To eliminate any redundant computation and maintain the temporal continuity of the same objects between two consecutive frames, the chromosomes are started from the spatial segmentation result of the previous frame, and then only unstable chromosomes corresponding to the moving object parts are evolved. Experiment results demonstrate the effectiveness of the proposed method.

The retrieval of video clips from multimedia databases has been increasingly spotlighted. Texts in videos include useful information for automatic annotation or indexing. Text location is the first step for recognizing the textual information. This paper proposes a neural network-based text location method for news video indexing. Text can be characterized by texture, location, alignment, and font size. The proposed method classifies text pixels and non-text pixels using a network that operates as a set of texture discrimination filters. We find and locate text regions using histogram analysis after removing errors in the classification results. Experimental results show that the proposed method is effective at locating texts.

Extracting a license plate is an important stage in automatic vehicle identification. It is very difficult because vehicle images are usually degraded and processing the images is computationally intensive. We propose a new method to extract the plate region using a distributed genetic algorithm. The algorithm offers robustness in dealing with deformation of vehicle images and inherent parallelism to improve the processing time. A test with seventy images shows an extraction rate of 92.8%, working well within real world situations. This results suggest that the proposed method is pertinent to be put into practical use.

This paper proposes an efficient method for on-line recognition of cursive Korean characters. Strokes, primitive components of Korean characters, are usually warped into a cursive form and classifying them is very difficult. To deal with such cursive strokes, we consider them as a recognition unit and automatically classify them by using an ART-2 neural network. The neural network has the advantage of assembling similar patterns together to form classes in a self-organized manner. This ART-2 stroke classifier contributes to high stroke recognition rate and less recognition time. A database for character recognition is also dynamically constructed with a tree structure, and a new character can be included simply by adding a new sequence to it. Character recognition is achieved by traversing the database with a sequence of recognized strokes and positional relations between the strokes. To verify the performance of the system, we tested it on 17,500 handwritten characters, and obtained a good recognition rate of 96.8% and a speed of 0.52 second per character. This results suggest that the proposed method is pertinent to be put into practical use.

The authors propose an efficient method for on-line recognition of run-on Korean characters. The method uses a set of extended primitive strokes and fuzzy membership functions to extract cursive strokes. To separate a character from run-on characters they construct character separation rules and a generalized character list. With a sequence of stroke codes and their positional relations computed, the method searches the target character on a generalized character list. A test with 17500 characters shows a recognition rate of 98.4% with a speed of 0.3 second per character.

An automatic recognition method of a car license plate using color image processing is presented. At first, background colors of a plate are extracted from an input car image. A neural network is used for more stable extraction. To find a plate region, a fixed ratio of horizontal and vertical length of a plate is used. To recognize characters in a plate, template matching and postprocessing techniques are used. Since the proposed method does not depend on line information of a plate it is very robust to boundary deformation. Also, this method is strong enough to deal with a car's image which has many similar regions with a plate.>