Seongjin Park

A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma

The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further examination of the RHOA mutation encoding p.Gly17Val in 239 lymphoma samples showed that the mutation was specific to T cell lymphoma and was absent from B cell lymphoma. We demonstrate that the RHOA mutation encoding p.Gly17Val, which was found in 53.3% (24 of 45) of the AITL cases examined, is oncogenic in nature using multiple molecular assays. Molecular modeling and docking simulations provided a structural basis for the loss of GTPase activity in the RHOA Gly17Val mutant. Our experimental data and modeling results suggest that the RHOA mutation encoding p.Gly17Val is a driver mutation in AITL. On the basis of these data and through integrated pathway analysis, we build a comprehensive signaling network for AITL oncogenesis.

Programming of Plant Leaf Senescence with Temporal and Inter-Organellar Coordination of Transcriptome in Arabidopsis.

RNA-seq analysis of total and small RNAs throughout the lifespan of Arabidopsis leaves revealed that leaf senescence proceeds with tight temporal and distinctive inter-organellar coordination of transcriptomes. Plant leaves, harvesting light energy and fixing CO2, are a major source of foods on the earth. Leaves undergo developmental and physiological shifts during their lifespan, ending with senescence and death. We characterized the key regulatory features of the leaf transcriptome during aging by analyzing total- and small-RNA transcriptomes throughout the lifespan of Arabidopsis (Arabidopsis thaliana) leaves at multidimensions, including age, RNA-type, and organelle. Intriguingly, senescing leaves showed more coordinated temporal changes in transcriptomes than growing leaves, with sophisticated regulatory networks comprising transcription factors and diverse small regulatory RNAs. The chloroplast transcriptome, but not the mitochondrial transcriptome, showed major changes during leaf aging, with a strongly shared expression pattern of nuclear transcripts encoding chloroplast-targeted proteins. Thus, unlike animal aging, leaf senescence proceeds with tight temporal and distinct interorganellar coordination of various transcriptomes that would be critical for the highly regulated degeneration and nutrient recycling contributing to plant fitness and productivity.

Epidermolysis bullosa acquisita in childhood – a case mimicking chronic bullous dermatosis of childhood

Epidermolysis bullosa acquisila (EBA) is rarely reported in childhood, hut we mm describe a 6‐year‐old Korean girl with the condition. She presented with multiple tense bullae annularly distributed on the perioral, periorbital and genital areas, and was successfully treated with dapsoae. The clinical and histological features were similar to those of chronic bullous dermatosis of childhood. We review seven previously reported childhood EBA cases and contrast their features with those of adult EBA. We suggest that some childhood EBA is different from the adult form and shares features with chronic bullous dermatosis of childhood.

VnD: a structure-centric database of disease-related SNPs and drugs

Numerous genetic variations have been found to be related to human diseases. Significant portion of those affect the drug response as well by changing the protein structure and function. Therefore, it is crucial to understand the trilateral relationship among genomic variations, diseases and drugs. We present the variations and drugs (VnD), a consolidated database containing information on diseases, related genes and genetic variations, protein structures and drug information. VnD was built in three steps. First, we integrated various resources systematically to deduce catalogs of disease-related genes, single nucleotide polymorphisms (SNPs), protein mutations and relevant drugs. VnD contains 137 195 disease-related gene records (13 940 distinct genes) and 16 586 genetic variation records (1790 distinct variations). Next, we carried out structure modeling and docking simulation for wild-type and mutant proteins to examine the structural and functional consequences of non-synonymous SNPs in the drug-related genes. Conformational changes in 590 wild-type and 4437 mutant proteins from drug-related genes were included in our database. Finally, we investigated the structural and biochemical properties relevant to drug binding such as the distribution of SNPs in proximal protein pockets, thermo-chemical stability, interactions with drugs and physico-chemical properties. The VnD database, available at http://vnd.kobic.re.kr:8080/VnD/ or vandd.org, would be a useful platform for researchers studying the underlying mechanism for association among genetic variations, diseases and drugs.

Fast 2d-3d point-based registration using GPU-Based preprocessing for image-guided surgery

We propose a 2D-3D point-based registration method that provides fast and efficient alignment of X-ray fluoroscopy and CT images. Our method is divided into two procedures: pre-operative and intra-operative procedures. For pre-operative procedures, we generate digitally reconstructed radiographs (DRRs) from 3D volume using graphics hardware. In intra-operative procedures, we perform a hierarchical registration that includes in-plane registration using principal axes method and out-plane registration using minimal error searching method in spherical coordinates. This method reduces a degree of freedom from 6-DOF to 2-DOF. Experimental results using 2 cardiac phantoms show that our DRRs generation method is more than 150 times faster than software-based ray casting methods, and our hierarchical registration technique effectively matches DRRs and 2D images.

miRseqViewer: multi-panel visualization of sequence, structure and expression for analysis of microRNA sequencing data

SUMMARY Deep sequencing of small RNAs has become a routine process in recent years, but no dedicated viewer is as yet available to explore the sequence features simultaneously along with secondary structure and gene expression of microRNA (miRNA). We present a highly interactive application that visualizes the sequence alignment, secondary structure and normalized read counts in synchronous multipanel windows. This helps users to easily examine the relationships between the structure of precursor and the sequences and abundance of final products and thereby will facilitate the studies on miRNA biogenesis and regulation. The project manager handles multiple samples of multiple groups. The read alignment is imported in BAM file format. Implemented features comprise sorting, zooming, highlighting, editing, filtering, saving, exporting, etc. Currently, miRseqViewer supports 84 organisms whose annotation is available at miRBase. AVAILABILITY AND IMPLEMENTATION miRseqViewer, implemented in Java, is available at https://github.com/insoo078/mirseqviewer or at http://msv.kobic.re.kr. CONTACT sanghyuk@ewha.ac.kr.

Parallelized Seeded Region Growing Using CUDA

This paper presents a novel method for parallelizing the seeded region growing (SRG) algorithm using Compute Unified Device Architecture (CUDA) technology, with intention to overcome the theoretical weakness of SRG algorithm of its computation time being directly proportional to the size of a segmented region. The segmentation performance of the proposed CUDA-based SRG is compared with SRG implementations on single-core CPUs, quad-core CPUs, and shader language programming, using synthetic datasets and 20 body CT scans. Based on the experimental results, the CUDA-based SRG outperforms the other three implementations, advocating that it can substantially assist the segmentation during massive CT screening tests.

Physically Based Nonrigid Registration Using Smoothed Particle Hydrodynamics: Application to Hepatic Metastasis Volume-Preserving Registration

Recent advances in computing hardware have enabled the application of physically based simulation techniques to various research fields for improved accuracy. In this paper, we present a novel physically based nonrigid registration method using smoothed particle hydrodynamics for hepatic metastasis volume-preserving registration between follow-up liver CT images. Our method models the liver and hepatic metastasis as a set of particles carrying their own physical properties. Based on the fact that the hepatic metastasis is stiffer than other normal cells in the liver parenchyma, the candidate regions of hepatic metastasis are modeled with particles of higher stiffness compared to the liver parenchyma. Particles placed in the liver and candidate regions of hepatic metastasis in the source image are transformed along a gradient vector flow-based force field calculated in the target image. In this transformation, the particles are physically interacted and deformed by a novel deformable particle method which is proposed to preserve the hepatic metastasis to the best. In experimental results using ten clinical datasets, our method matches the liver effectively between follow-up CT images as well as preserves the volume of hepatic metastasis almost completely, enabling the accurate assessment of the volume change of the hepatic metastasis. These results demonstrated a potential of the proposed method that it can deliver a substantial aid in measuring the size change of index lesion (i.e., hepatic metastasis) after the chemotheraphy of metastasis patients in radiation oncology.

Comparison of three image comparison methods for the visual assessment of the image fidelity of compressed computed tomography images

PURPOSE This study aimed to comparatively evaluate three different image comparison methods: alternate display without an intervening blank image (AWOB), alternate display with an intervening blank image (AWB), and side-by-side display (SSD), in terms of the perceptual sensitivity to image differences between Joint Photographic Experts Group 2000 (JPEG2000) compressed body CT images and their originals. METHODS A total of 50 body CT images obtained with five different scan protocols (5-mm-thick abdomen, 0.67-mm-thick abdomen, 5-mm-thick lung, 0.67-mm-thick lung, and 5-mm-thick low-dose lung) were compressed to one of five compression ratios (reversible, 6:1, 8:1, 10:1, and 15:1) using JPEG2000 algorithm. The fidelity of the compressed images was visually assessed on a four-grade scale independently by five radiologists using each of the three image comparison methods of AWOB, AWB, and SSD. The fidelity grading results for the 40 irreversibly compressed images were compared between the three image comparison methods using the Friedman tests with post hoc Tukey tests. The number of image pairs with no perceptible difference was compared using the exact tests for paired proportions. The time required for the fidelity assessment for all of the 50 compressed images was also compared using the Friedman tests with post hoc Tukey tests. RESULTS For the 40 irreversibly compressed images, the fidelity grade was significantly lower for AWOB than for AWB or SSD (p < 0.01 for all readers); however, there was no significant difference between AWB and SSD (p-value range, 0.06-0.92). The percentage of image pairs with no perceptible difference tended to be smaller for AWOB than for AWB (p < 0.01 for all readers) or SSD (p < 0.01 for readers 1-3, p = 0.04 for reader 4, and p = 0.23 for reader 5). However, there was no significant difference between AWB and SSD (p-value range, 0.12- >0.99). For all of the 50 compressed images, the fidelity grading time significantly increased in the order of AWOB, SSD, and AWB. CONCLUSIONS In assessing the image fidelity of JPEG2000 compressed body CT images, AWOB yields lower fidelity grade and requires less fidelity grading time than AWB or SSD, indicating that AWOB is most sensitive to image differences among of them.

Graphics Hardware-Based Level-Set Method for Interactive Segmentation and Visualization

This paper presents an efficient graphics hardware-based method to segment and visualize level-set surfaces as interactive rates. Our method is composed of memory manager, level-set solver, and volume renderer. The memory manager which performs in CPU generates page table, inverse page table and available page stack as well as process the activation and inactivation of pages. The level-set solver computes only voxels near the iso-surface. To run efficiently on GPUs, volume is decomposed into a set of small pages. Only those pages with non-zero derivatives are stored on GPU. These active pages are packed into a large 2D texture. The level-set partial differential equation (PDE) is computed directly on this packed format. The memory manager is used to help managing the packing of the active data. The volume renderer performs volume rendering of the original data simultaneouly with the evo-lving level set in GPU. Experimental results using two chest CT datasets show that our graphics hardware-based level-set method is much faster than software-based one.