MOTIVATION: Characterizing cancer subclones is crucial for the ultimate conquest of cancer. Thus, a number of bioinformatic tools have been developed to infer heterogeneous tumor populations based on genomic signatures such as mutations and copy number variations. Despite accumulating evidence for the significance of global DNA methylation reprogramming in certain cancer types including myeloid malignancies, none of the bioinformatic tools are designed to exploit subclonally reprogrammed methylation patterns to reveal constituent populations of a tumor. In accordance with the notion of global methylation reprogramming, our preliminary observations on acute myeloid leukemia (AML) samples implied the existence of subclonally occurring focal methylation aberrance throughout the genome. RESULTS: We present PRISM, a tool for inferring the composition of epigenetically distinct subclones of a tumor solely from methylation patterns obtained by reduced representation bisulfite sequencing. PRISM adopts DNA methyltransferase 1-like hidden Markov model-based in silico proofreading for the correction of erroneous methylation patterns. With error-corrected methylation patterns, PRISM focuses on a short individual genomic region harboring dichotomous patterns that can be split into fully methylated and unmethylated patterns. Frequencies of such two patterns form a sufficient statistic for subclonal abundance. A set of statistics collected from each genomic region is modeled with a beta-binomial mixture. Fitting the mixture with expectation-maximization algorithm finally provides inferred composition of subclones. Applying PRISM for two AML samples, we demonstrate that PRISM could infer the evolutionary history of malignant samples from an epigenetic point of view. AVAILABILITY AND IMPLEMENTATION: PRISM is freely available on GitHub (https://github.com/dohlee/prism). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The use of vaccinia virus, an oncolytic virus, in cancer immune therapy enhances the overall immune response. The mechanism of immune response against cancer and virus infection is similar. We found sequence relationships between vaccinia virus proteins and human proteins that are often regarded as hallmarks of cancer. From comparing human and vaccinia virus protein sequences, genetically engineered viruses associated with immune response have been used for cancer immune therapy in many clinical trials. Using published papers about cancer immunology, we classified proteins as either positively or negatively associated with cancer immune therapy. We searched for sequence relationships between human proteins and vaccinia virus proteins that are related to the classified proteins.

UNLABELLED: COMPAM is a tool for visualizing relationships among multiple whole genomes by combining all pairwise genome alignments. It displays shared conserved regions (blocks) and where these blocks occur (edges) as block relation graphs which can be explored interactively. An unannotated genome, e.g. can then be explored using information from well-annotated genomes, COG-based genome annotation and genes. COMPAM can run either as a stand-alone application or through an applet that is provided as service to PLATCOM, a toolset for whole genome comparative analysis, where a wide variety of genomes can be easily selected. Features provided by COMPAM include the ability to export genome relationship information into file formats that can be used by other existing tools. AVAILABILITY: http://bio.informatics.indiana.edu/projects/compam/

A majority of urban traffic signal systems including coordinated actuated signals deploy multiple signal timing plans to account for traffic demand changes over time during a day (i.e., off peak, morning peak, mid day, evening peak, and night). A recent study proposed a data driven methodology that develops such time of day (TOD) break points using a clustering algorithm. One disadvantage of such statistical approaches was that they often produce clusters with few data points (i.e., infeasible time-of-day interval). This paper presents an enhancement of data driven methodology that determines optimal break points for TOD traffic signal control. In order to overcome such drawback, a genetic algorithm based clustering is proposed and evaluated through the performance of actual timing plan under microscopic simulation program, SIMTRAFFIC. The study results indicate that the proposed method can eliminate infeasible TOD intervals and its TOD-based timing plan produced comparable performances to those existing TOD intervals.

Realistic representation of various effects which appear in the real world paintings can be used for several applications like animation or education. To generate oriental paintings, numerous studies have focused on model-based approaches. In this paper, a new model-based approach for oriental paintings is described. To represent the diffusion effects, we propose local equilibrium model (LEM) which is a method to calculate the movement of water and ink effectively. In addition, we propose a paper model with fiber mesh structure and three layers structure on each cell. With this layer model, overlapped strokes can be well represented. A brush model proposed supports several brush effects like shading.

So far there have been models for generating handwriting scripts of western languages. Since the basic structure of oriental languages such as Chinese, Japanese and Korean, is quite different from that of alphabet-based western languages, western handwriting models cannot be applied directly to oriental languages except for a few models. In this paper, we propose a new generation model for generating Korean handwriting scripts. For this we choose 11 characteristic parameters which determine the shape of handwriting scripts. These parameters were selected experimentally by investigating ample Korean scripts. Furthermore we propose the Beta-velocity model to simulate the cursive stroke movement by manipulating curvilinear and cursive connection for consecutive strokes within a letter or a word. In order to generate these oriental cursive strokes, we adopted Beta distribution curve basis which enables one to make easy asymmetric velocity profile. By combining all these features, we synthesize various handwriting Korean scripts by controlling 11 characteristic parameters. In the final section of this paper, we give experimental results. These easy-to-synthesize Korean scripts can be used in evaluating off-line character recognition system and a word processor by supporting handwriting-style fonts.