Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. @*Materials and Methods@#A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. @*Results@#The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. @*Conclusion@#The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Identifying Minimum Data Sets of Oral Mucous Integrity Assessment for Documentation Systematization / 중환자간호학회지

PURPOSE: The purpose of this study was to identify minimum data sets for oral mucous integrity-related documentation and to analyze nursing records for oral care.METHODS: To identify minimum data sets for oral status, the authors reviewed 26 assessment tools and a practical guideline for oral care. The content validity of the minimum data sets was assessed by three nurse specialists. To map the minimum data sets to nursing records, the authors examined 107 nursing records derived from 44 patients who received chemotherapy or hematopoietic stem cell transplantation in one tertiary hospital.RESULTS: The minimum data sets were 10 elements such as location, mucositis grade, pain, hygiene, dysphagia, exudate, inflammation, difficulty speaking, and moisture. Inflammation contained two value sets: type and color. Mucositis grade, pain, dysphagia and inflammation were recorded well, accounting for a complete mapping rate of 100%. Hygiene (100%) was incompletely mapped, and there were no records for exudate (83.2%), difficulty speaking (99.1%), or moisture (88.8%).CONCLUSION: This study found that nursing records on oral mucous integrity were not sufficient and could be improved by adopting minimum data sets as identified in this study.

Computed Tomographic Features of Lung Parenchyma Over Time after Cardiopulmonary Resuscitation

PURPOSE@#To identify the key CT features of lung parenchyma over time after cardiopulmonary resuscitation (CPR).@*MATERIALS AND METHODS@#In total, 72 patients underwent CT after CPR. Because the median time from return of spontaneous circulation (ROSC) to CT was 1 h 3 min, we divided patients into two groups: ≤ 1 h (group 1) and > 1 h (group 2), based on the ROSC to CT time. We analyzed and compared various lung parenchymal CT findings between groups.@*RESULTS@#Each group included 36 patients. Using statistical analysis, we identified seven statistically significant imaging features. Gradient (p = 0.010), lobular gradient (p = 0.017), diffuse pattern (p = 0.000), upper distribution (p = 0.032), and peripheral portion sparing (p = 0.000) were more common in group 1 than in group 2. Dependent density (p = 0.010) and lobular consolidation (p = 0.010) were more common in group 2 than in group 1.@*CONCLUSION@#The gradient and lobular gradient tended to disappear over time after ROSC. In terms of distribution, a diffuse pattern with upper predominance and peripheral portion sparing tended to disappear over time. However, the dependent density and lobular consolidation tended to increase over time in the lung parenchyma after CPR.

Shifting of Centricity: Qualitative Meta Synthetic Approach on Caring Experience of Family Members of Patients with Dementia

PURPOSE: This study aimed to synthesize the caring experiences of Korean family members of patients with dementia through a qualitative meta-synthesis method. METHODS: By searching through nine Korean and English databases, we compared 37 qualitative studies on caring experiences of family members of patients with dementia. The selected studies were synthesized through meta-synthesis, proposed by Sandelowski and Barroso (2007). RESULTS: The meta-synthesis elicited four themes: tough life due to care for patients, changes in relationships, adaptation to caregiver's roles, and new perspectives of life through personal growth. Caregivers were shocked when a sudden diagnosis of dementia was made prior to any preparation on their part. They were tied to their patients all the time and their mind and body got exhausted. Their relationship with patients began to change and they looked at them differently. They experienced conflicts with the other non-caring family members and were alienated from them. They were also socially isolated. However, by building their own care strategies and utilizing social resources, they gradually adapted to their caregiver roles. Finally, they experienced personal growth and acquired a new perspective toward life by accepting their roles and finding meaning in their lives. Shifting the caregiver's centricity from themselves to the patient was the process of becoming human beings who actively constructed their realities while giving meaning to their painful lives and interacting with the environment. CONCLUSION: The results of the study can be useful for nurses in understanding the experiences of caregivers of the patients with dementia and in providing them with practical interventions.

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study / 예방의학회지

OBJECTIVES@#The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes.@*METHODS@#We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others.@*RESULTS@#Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%).@*CONCLUSIONS@#Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Development and Evaluation of a Korean Version of a Thyroid-Specific Quality-of-Life Questionnaire Scale in Thyroid Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to develop a Korean version of the self-reported thyroid-specific quality of life (QoL) questionnaire for thyroid cancer patients (KT-QoL), and to evaluate its reliability and validity. MATERIALS AND METHODS: Two hundred seventy-two patients who underwent thyroidectomy from January to December 2010 were recruited in this study. The original version of the thyroid QoL was translated into Korean and evaluated for its reliability and validity. Using the developed KT-QoL, the postoperative QoL was evaluated until postoperative 1 year. RESULTS: At the preoperative baseline, the item internal consistency (IIC) ranged from −0.19 to 0.76, with low IIC values for items 2, 17, and 27. Item discriminant validity ranged from 86% to 97%. These values were similar at the postoperative periods. The internal consistency reliability (Cronbach's α) was high for all dimensions, ranging from 0.90 to 0.95. The test-retest reliability (intraclass correlation coefficient) was acceptable (0.74-0.82). The external validity examined by the correlation between the item 1j (voice changes) of KT-QoL and the voice handicap index-30 ranged from 0.51 to 0.75. Patients' QoL scores decreased after surgery, which demonstrated the sensitivity of the questionnaire. The QoL scores in patients with lobectomy showed best QoL scores postoperatively and those with receiving radioactive iodine still showed decreased QoL scores along the postoperative periods. CONCLUSION: These results demonstrate that KT-QoL is a valid instrument for evaluating QoL of Korean patients with thyroid cancer.

Effect of a Patient Illness Narrative on Knowledge about Schizophrenia, Attitudes toward Mental Illness, and Learning Satisfaction / 정신간호학회지

PURPOSE: The aim of this study was to identify effects of a psychiatric and mental health nursing class to improve knowledge about schizophrenia, attitudes toward mental illness, and learning satisfaction after using an illness narrative of a patient with schizophrenia. METHODS: This study was in nonequivalent control group and a pretest-posttest design. Of the 88 nursing students, the 34 in the experimental group received 5 hours of lectures on schizophrenia plus 2 hours of learning using a patient's illness narrative. The control group (n=54) received only the 5 hours of lectures on schizophrenia. During September, 2017, an online survey was used to collect data before and after the intervention. Data were analyzed using t-tests and Mann-Whitney U tests with SPSS Statistics version 22.0. RESULTS: There were no differences for knowledge on schizophrenia or for attitudes toward mental illness between the experimental group and the control group after the intervention. However, learning satisfaction was significantly higher in the experimental group compared to the control group (Z=−2.18, p=.029). CONCLUSION: Findings indicate that patient illness narratives could be a useful tool to improve learning satisfaction in nursing students. Therefore, using patient illness narratives in nursing classes is recommended.

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study / 예방의학회지

OBJECTIVES: The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes. METHODS: We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. RESULTS: Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%). CONCLUSIONS: Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Validity and Reliability of the Nurses' Self-Concept Instrument (NSCI) for Registered Nurses in Long-term Care Hospitals

PURPOSE: The purpose of this study was to evaluate the validity and reliability of the Korean Version of the Nurses' Self-Concept Instrument (NSCI) geriatric hospital nurses in Korea. METHODS: Bilingual nursing professionals performed translation and back-translation. Reliability and validity of the content and construction of the instrument were confirmed. Internal consistency reliability was determined. Construction and concurrent validity were verified using factor analysis and correlation coefficients. RESULTS: The total 14 items for the Korean version of the Nurses' Self-Concept Instrument (NSCI) were retained through item analysis. In explanatory factor analysis, four subcategories were proposed with their names of each factor: ‘Leadership’, ‘Staff relation’, ‘Knowledge’, and ‘Care’. The four factors accounted for 78.81% of the variances. The Cronbach's α regarding internal consistency were .77~.91 for the NSCI subscales. Correlation among four subcategories ranged .62~.84. CONCLUSION: The findings show that the Korean version of the Nurses' Self-Concept Instrument is reliable and valid for measuring professional Self-Concept of geriatric hospital nurses in Korea.

15-Hydroxyprostaglandin dehydrogenase as a marker in colon carcinogenesis: analysis of the prostaglandin pathway in human colonic tissue

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2), 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and microsomal prostaglandin E synthase-1 (mPGEs-1) regulate prostaglandin E₂ (PGE₂) expression and are involved in colon carcinogenesis. We investigated the expression of PGE₂ and its regulating genes in sporadic human colon tumors and matched normal tissues. METHODS: Twenty colonic adenomas and 27 colonic adenocarcinomas were evaluated. COX-2 and 15-PGDH expression was quantified by real-time polymerase chain reaction. The expression of PGE₂ and mPGEs-1 was measured using enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: The expression of COX-2, mPGEs-1, and PGE₂ did not differ between the adenomas and matched distant normal tissues. 15-PGDH expression was lower in adenomas than in the matched normal colonic tissues (P<0.001). In adenocarcinomas, mPGEs-1 and PGE₂ expression was significantly higher (P<0.001 and P=0.020, respectively), and COX-2 expression did not differ from that in normal tissues (P=0.207). 15-PGDH expression was significantly lower in the normal colonic mucosa from adenocarcinoma patients than in the normal mucosa from adenoma patients (P=0.018). CONCLUSIONS: Early inactivation of 15-PGDH, followed by activation of COX-2 and mPGEs-1, contributes to PGE₂ production, leading to colon carcinogenesis. 15-PGDH might be a novel candidate marker for early detection of field defects in colon carcinogenesis.

Evaluation of the learning curve for external cephalic version using cumulative sum analysis

OBJECTIVE: We evaluated the learning curve for external cephalic version (ECV) using learning curve-cumulative sum (LC-CUSUM) analysis. METHODS: This was a retrospective study involving 290 consecutive cases between October 2013 and March 2017. We evaluated the learning curve for ECV on nulli and over para 1 group using LC-CUSUM analysis on the assumption that 50% and 70% of ECV procedures succeeded by description a trend-line of quadratic function with reliable R² values. RESULTS: The overall success rate for ECV was 64.8% (188/290), while the success rate for nullipara and over para 1 groups was 56.2% (100/178) and 78.6% (88/112), respectively. ‘H’ value, that the actual failure rate does not differ from the acceptable failure rate, was −3.27 and −1.635 when considering ECV success rates of 50% and 70%, respectively. Consequently, in order to obtain a consistent 50% success rate, we would require 57 nullipara cases, and in order to obtain a consistent 70% success rate, we would require 130 nullipara cases. In contrast, 8 to 10 over para 1 cases would be required for an expected success rate of 50% and 70% on over para 1 group. CONCLUSION: Even a relatively inexperienced physician can experience success with multipara and after accumulating experience, they will manage nullipara cases. Further research is required for LC-CUSUM involving several practitioners instead of a single practitioner. This will lead to the gradual implementation of standard learning curve guidelines for ECV.

Perceptions of Healthcare Workers of Health Risks of Electromagnetic Fields

BACKGROUND: This study assessed the perceptions of healthcare staff of the health risks of exposure to electromagnetic fields (EMF). METHODS: In total, 328 healthcare workers (e.g., physicians, nurses, medical students, and paramedics) completed a self-administered questionnaire. The questionnaire assessed the following: risk perceptions of 17 environmental factors as potential health threats; EMF sources; information for the potential risks of EMF; and thoughts on how to protect the public from potential EMF-related health risks. RESULTS: Of the included environmental factors, high-tension power lines and mobile phone handsets were ranked as the second and fourth lowest perceived risk, respectively. Approximately 60% of respondents were concerned about the potential health risks of EMF and dissatisfied with the information they received. The main reason for dissatisfaction was insufficient information. The most frequently cited action was that the government should review the available scientific evidence on potential EMF-related health risks. CONCLUSIONS: Having scientific basis through well-designed researches and providing accurate information to the public on the potential health risks of EMF will be important in the future.

15-Hydroxyprostaglandin Dehydrogenase in Colorectal Mucosa as a Potential Biomarker for Predicting Colorectal Neoplasms

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is downregulated during the early stages of colorectal carcinogenesis. The aim of the present study was to investigate the potential role of 15-PGDH in normal-appearing colorectal mucosa as a biomarker for predicting colorectal neoplasms. We obtained paired tumor and normal tissues from the surgical specimens of 32 sporadic colorectal cancer patients. mRNA expression of 15-PGDH was measured using a quantitative real-time PCR assay. We evaluated the association between 15-PGDH mRNA expression in normal-appearing mucosa, the presence of synchronous adenoma, and the cumulative incidence of metachronous adenoma. The relative 15-PGDH expression of normal-appearing mucosa in patients with synchronous adenoma was significantly lower than in patients without synchronous adenoma (0.71 vs 1.00, P = 0.044). The patients in the lowest tertile of 15-PGDH expression in normal-appearing mucosa were most likely to have synchronous adenoma (OR: 10.5, P = 0.024). Patients with low 15-PGDH expression in normal-appearing mucosa also demonstrated more advanced stage colorectal cancer (P = 0.045). However, there was no significant difference in the cumulative incidence of metachronous adenoma according to 15-PGDH mRNA expression in normal-appearing mucosa (P = 0.333). Hence, 15-PGDH in normal-appearing colorectal mucosa can be a useful biomarker of field effect for the prediction of sporadic synchronous neoplasms.

The Factors Influencing Quality of Life in Women with Breast Cancer

PURPOSE: The purpose of the study was to identify the influence of hope, resilience, and spousal support on quality of life in women with breast cancer. METHODS: A predictive correlational design was used. The data were collected by questionnaires from a convenience sample of 163 women with breast cancer in 2012. The data were analyzed using descriptive statistics, t-tests, ANOVA, Pearson's Correlation Coefficients, and stepwise multiple regression. RESULTS: Mean age of the participants was 51.5+/-6.39 and 46.0% reported to have stage II at diagnosis and 40.5% were more than 5 years since diagnosis. The quality of life was different by age and type of surgery. Hope, resilience, spousal support, and quality of life were significantly correlated each other (r=.35-.64, p<.01). Quality of life accounted for 23.4% of the variance by resilience, spousal support, and type of surgery. The most important factor was resilience, which explained 18.9% of the variation. CONCLUSION: The results of the study show the importance of resilience in explaining the quality of life in Korean women with breast cancer. Thus, oncology nurses should focus on resilience to develop and implement more effective interventions to improve patients' quality of life.

Relationship between Mental Health Status and Suicidal Thinking among Cancer Patients / 재활간호학회지

PURPOSE: This study was to examine the relationship between mental health status and suicidal thinking among cancer patients. METHODS: The data set of the 4th Korea National Health and Nutrition Survey (2009) was used and 230 subjects with cancers were included in the present study. Using SPSS/WIN 18.0 program, data were analyzed with descriptive statistics, chi2 test and logistic regression analysis. RESULTS: About one-third of subjects had stress, symptoms of depression and suicidal thinking. Female had more suicidal thinking than male (chi2=5.44, p=.020). In addition, subjects with high income level had more thinking about suicide compared with those in low income level (chi2=7.54, p=.023). There was a significant difference in suicidal thinking according to the educational levels (chi2=13.25, p=.004). In the logistic regression analysis, it was indicated that gender, depression and stress were significant predictors on suicidal thinking, accounting for 26.7~38.1%. CONCLUSION: From the findings in this study, it was suggested that the healthcare providers should try to improve their mental health status in order to prevent suicidal thinking among the individuals diagnosed with cancer.

Rapidly Growing Bilateral Pseudoangiomatous Stromal Hyperplasia of the Breast

A tumoral pseudoangiomatous stromal hyperplasia (PASH) that causes huge breast enlargement is very rare. Only two cases of huge tumoral PASHs have been reported in the English medical literature. We report here on a surgically confirmed case of bilateral huge tumoral PASH in a 47-year-old woman, and we present the imaging and histopathology findings. We also review the relevant medical literature.

Near-Infrared Fluorescence Imaging Using a Protease-Specific Probe for the Detection of Colon Tumors

BACKGROUND/AIMS: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. METHODS: We utilized two murine colon cancer models: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. RESULTS: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. CONCLUSIONS: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.

1-Year Follow-Up of Mindfulness-Based Cognitive Therapy in Patients with Generalized Anxiety Disorder or Panic Disorder / 신경정신의학

OBJECTIVES: Mindfulness-base cognitive therapy (MBCT) has been used to treat patients with depression to prevent relapse. The purpose of this study was to examine the effectiveness of Mindfulness- Base Cognitive Therapy for patients who suffer with generalized anxiety disorder or panic disorder for 1 year. METHODS: 19 patients with generalized anxiety disorder or panic disorder were assigned to receive MBCT for a period of 8 weeks. The Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI) were used at 0 weeks, 8 weeks and 1 year to assess the results. RESULTS: MBCT demonstrated significantly decreases on all the anxiety scale scores (HAM-A, p=0.00 ; BAI, p=0.00) and depressive scale scores (HAM-D, p=0.00 ; BDI, p=0.00). The patients who received 8-week of MBCT showed a higher remission rate (15/19, 78%) during the 1-year followup period. CONCLUSION: MBCT may be effective at relieving the anxiety and depressive symptoms of patients who suffer with generalized anxiety disorder or panic disorder for 1 year. However, further well-designed controlled trials are needed to assess the value of MBCT.

FCAnalyzer: A Functional Clustering Analysis Tool for Predicted Transcription Regulatory Elements and Gene Ontology Terms

Numerous studies have reported that genes with similar expression patterns are co-regulated. From gene expression data, we have assumed that genes having similar expression pattern would share similar transcription factor binding sites (TFBSs). These function as the binding regions for transcription factors (TFs) and thereby regulate gene expression. In this context, various analysis tools have been developed. However, they have shortcomings in the combined analysis of expression patterns and significant TFBSs and in the functional analysis of target genes of significantly overrepresented putative regulators. In this study, we present a web-based A Functional Clustering Analysis Tool for Predicted Transcription Regulatory Elements and Gene Ontology Terms (FCAnalyzer). This system integrates microarray clustering data with similar expression patterns, and TFBS data in each cluster. FCAnalyzer is designed to perform two independent clustering procedures. The first process clusters gene expression profiles using the K-means clustering method, and the second process clusters predicted TFBSs in the upstream region of previously clustered genes using the hierarchical biclustering method for simultaneous grouping of genes and samples. This system offers retrieved information for predicted TFBSs in each cluster using Match(TM) in the TRANSFAC database. We used gene ontology term analysis for functional annotation of genes in the same cluster. We also provide the user with a combinatorial TFBS analysis of TFBS pairs. The enrichment of TFBS analysis and GO term analysis is statistically by the calculation of P values based on Fisher's exact test, hypergeometric distribution and Bonferroni correction. FCAnalyzer is a web-based, user-friendly functional clustering analysis system that facilitates the transcriptional regulatory analysis of co-expressed genes. This system presents the analyses of clustered genes, significant TFBSs, significantly enriched TFBS combinations, their target genes and TFBS-TF pairs.

Calibrating Thresholds to Improve the Detection Accuracy of Putative Transcription Factor Binding Sites

To understand the mechanism of transcriptional regulation, it is essential to detect promoters and regulatory elements. Various kinds of methods have been introduced to improve the prediction accuracy of regulatory elements. Since there are few experimentally validated regulatory elements, previous studies have used criteria based solely on the level of scores over background sequences. However, selecting the detection criteria for different prediction methods is not feasible. Here, we studied the calibration of thresholds to improve regulatory element prediction. We predicted a regulatory element using MATCH, which is a powerful tool for transcription factor binding site (TFBS) detection. To increase the prediction accuracy, we used a regulatory potential (RP) score measuring the similarity of patterns in alignments to those in known regulatory regions. Next, we calibrated the thresholds to find relevant scores, increasing the true positives while decreasing possible false positives. By applying various thresholds, we compared predicted regulatory elements with validated regulatory elements from the Open Regulatory Annotation (ORegAnno) database. The predicted regulators by the selected threshold were validated through enrichment analysis of muscle-specific gene sets from the Tissue-Specific Transcripts and Genes (T-STAG) database. We found 14 known muscle-specific regulators with a less than a 5% false discovery rate (FDR) in a single TFBS analysis, as well as known transcription factor combinations in our combinatorial TFBS analysis.