The Korean Bioinformation Center (KOBIC) is a national bioinformatics research center in Korea. We developed many bioinformatics algorithms and applications to facilitate the biological interpretation of OMICS data. Here we present an introduction to major bioinformatics resources of databases and tools developed at KOBIC. These resources are classified into three main fields: genome, proteome, and literature. In the genomic resources, we constructed several pipelines for next generation sequencing (NGS) data processing and developed analysis algorithms and web-based database servers including miRGator, ESTpass, and CleanEST. We also built integrated databases and servers for microarray expression data such as MDCDP. As for the proteome data, VnD database, WDAC, Localizome, and CHARMM_HM web servers are available for various purposes. We constructed IntoPub server and Patome database in the literature field. We continue constructing and maintaining the bioinformatics infrastructure and developing algorithms.
Computational Biology ; Genome ; Korea ; Proteome

MicroRNAs play an important role in regulating gene expression, but their target identification is a difficult task due to their short length and imperfect complementarity. Burge and coworkers developed a program called TargetScan that allowed imperfect complementarity and established a procedure favoring targets with multiple binding sites conserved in multiple organisms. We improved their algorithm in two major aspects - (i) using well-defined UTR (untranslated region) database, (ii) examining the extent of conservation inside the 3' UTR specifically. Average length in our UTR database, based on the ECgene annotation, is more than twice longer than the Ensembl. Then, TargetScan was used to identify putative binding sites. The extent of conservation varies significantly inside the 3' UTR. We used the "tight" tracks in the UCSC genome browser to select the conserved binding sites in multiple species. By combining the longer 3' UTR data, TargetScan, and tightly conserved blocks of genomic DNA, we identified 107 putative target genes with multiple binding sites conserved in multiple species, of which 85 putative targets are novel.
3' Untranslated Regions* ; Binding Sites ; DNA ; Gene Expression ; Genome ; Genomics* ; Methods ; MicroRNAs*

Fusion proteins resulting from chimeric sequences are excellent targets for therapeutic drug development. We developed a database of chimeric sequences by examining the genomic alignment of mRNA and EST sequences in the GenBank. We identified 688 chimeric mRNA and 20,998 chimeric EST sequences. Including EST sequences greatly expands the scope of chimeric sequences even though it inevitably accompanies many artifacts. Chimeric sequences are clustered according to the ECgene ID so that the user can easily find chimeric sequences related to a specific gene. Alignments of chimeric sequences are displayed as custom tracks in the UCSC genome browser. ChimerDB, available at http://genome.ewha.ac.kr/ECgene/ChimerDB/, should be a valuable resource for finding drug targets to treat cancers.
Artifacts ; Databases, Nucleic Acid* ; Genome ; RNA, Messenger ; Trans-Splicing ; Translocation, Genetic

Identification of fusion gene is of prominent importance in cancer research field because of their potential as carcinogenic drivers. RNA sequencing (RNA-Seq) data have been the most useful source for identification of fusion transcripts. Although a number of algorithms have been developed thus far, most programs produce too many false-positives, thus making experimental confirmation almost impossible. We still lack a reliable program that achieves high precision with reasonable recall rate. Here, we present FusionScan, a highly optimized tool for predicting fusion transcripts from RNA-Seq data. We specifically search for split reads composed of intact exons at the fusion boundaries. Using 269 known fusion cases as the reference, we have implemented various mapping and filtering strategies to remove false-positives without discarding genuine fusions. In the performance test using three cell line datasets with validated fusion cases (NCI-H660, K562, and MCF-7), FusionScan outperformed other existing programs by a considerable margin, achieving the precision and recall rates of 60% and 79%, respectively. Simulation test also demonstrated that FusionScan recovered most of true positives without producing an overwhelming number of false-positives regardless of sequencing depth and read length. The computation time was comparable to other leading tools. We also provide several curative means to help users investigate the details of fusion candidates easily. We believe that FusionScan would be a reliable, efficient and convenient program for detecting fusion transcripts that meet the requirements in the clinical and experimental community. FusionScan is freely available at http://fusionscan.ewha.ac.kr/.
Cell Line ; Dataset ; Exons ; Gene Fusion ; Sequence Analysis, RNA ; Translocation, Genetic

Mystic experience is highly evaluated so as to be called as core of experience in the religious world and also becomes the subject of concern among various social groups. Psychologists and psychiatrists are concerned about it, but because of its individuality and subjectivity, the scientific approach was difficult so that only the description of mystic experience has been researched so far. There is a current report saying that mystic experience is the one of the dissociative phenomenon. And there are a lot of reports saying that dissociation is related to childhood trauma experience and rises as much as psychopathological tendencies exist. Consequently, based on the reference that mystic experience is connected with dissociation, the study has been progressed to find out the level of dissociation, psychopathology and trauma experience for religious people who experienced mystic experience but excluding patients. Among them, it has been compared between group of non-mystic experience (n=35) and group of mystic experience (n=42). We used Dissociative Experience scale-Korean version (DES-K), Symptom Checklist-90-Revised (SCL-90-R), questionnaire about trauma. The result is that the group of mystic experience had a significantly higher tendency to have dissociation and trauma experience than group of non-mystic experience. However, the difference of psychopathology has not been found.
Humans ; Individuality ; Psychiatry ; Psychology ; Psychopathology ; Surveys and Questionnaires

Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

OBJECTIVES: In establishing policies for agricultural safety, evaluating injury burdens as well as investigating the rates and characteristics of work injury is important. This study investigated the types and characteristics of agricultural injury subjective burdens. METHODS: By analyzing the injured farmers identified in the 2013 Korean Farmers' Occupational Injury Survey, the burdens caused by injuries were categorized using one direct cost item (medical costs) and five indirect cost items (including productivity decreases and wage increases). Statistical differences among the burden items were analyzed using logistic regression analysis according to the characteristics of the farmers and their farm injuries. RESULTS: Among the subjective burdens indicated by the 457 injured farmers, disruption to work was most common. The major influences on each subjective burden item are as follows: for the item of disruption to work, age, time of injury occurrence, treatment period, and farming machine use were influential; for an increased family member's burden of farm works, the number of family members and treatment period were influential. Regarding cost burden of treatment, the results varied according to whether or not the patient was hospitalized and annual income. CONCLUSION: Subjective burdens induced by indirect costs rather than those induced by direct costs were found to be higher in ratio. In regard to each burden item, the results varied according to the characteristics of the farmers and their farm injuries. To support injured farmer, setting goals to reduce indirect cost burdens and preparing concrete methods is necessary.
Efficiency ; Humans ; Logistic Models ; Occupational Injuries ; Salaries and Fringe Benefits

BACKGROUND: Although the incidence of resistance to macrolides in group A streptococci (GAS) was low in the past, high incidences have now been reported from several countries. We tried to find out trends of the incidence of erythromycin-resistant GAS in Korea before and after adopting the separation of the dispensary from medical practice in the middle of the year 2000. METHODS: Five hundred thirty two isolates from children with suspected pharyngotonsillitis from 1998 through 2002 were serotyped by T-agglutination. Minimal inhibitory concentrations of 330 out of 532 isolates were determined by agar dilution methods. RESULTS: The prevalent T-serotypes were T12 (36.1%), T4 (12.8%), T1 (10.9%), T2/28 (8.8%), and nontypable (7.1%). Resistance rates to erythromycin (EM) by year were 46.2% in 1998, 18.4% in 1999, 15.4% in 2000, 27.6% in 2001, 36.5% in 2002. T12 in 1999 and 2000 were 36.4% and 25.9%, respectively, which seem to be lower than any other year. This relative low percentage of T12 is associated with increasing percentage of T1 in the same year. The frequency of T12, T1,and T4 were high in each group of isolates of Seoul and Masan. From this viewpoint, there was a similarity between the distribution of T-serotypes of both groups of Seoul and Masan. CONCLUSION: The frequency of serotype T12 and T4 of GAS were relatively high in Korea from 1998 through 2002. The low rate of EM resistance in 1999 and 2000 seemed to be caused by a sudden increase of T1. The increasing rate of EM resistance from 2000 to 2002 seemed to be caused by the increase in consumption of new macrolides and the increase of T12.
Agar ; Child ; Erythromycin ; Humans ; Incidence* ; Korea* ; Macrolides ; Seoul

Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.