Ho Sun Shon

Comparing the normalization methods for the differential analysis of Illumina high-throughput RNA-Seq data

BackgroundRecently, rapid improvements in technology and decrease in sequencing costs have made RNA-Seq a widely used technique to quantify gene expression levels. Various normalization approaches have been proposed, owing to the importance of normalization in the analysis of RNA-Seq data. A comparison of recently proposed normalization methods is required to generate suitable guidelines for the selection of the most appropriate approach for future experiments.ResultsIn this paper, we compared eight non-abundance (RC, UQ, Med, TMM, DESeq, Q, RPKM, and ERPKM) and two abundance estimation normalization methods (RSEM and Sailfish). The experiments were based on real Illumina high-throughput RNA-Seq of 35- and 76-nucleotide sequences produced in the MAQC project and simulation reads. Reads were mapped with human genome obtained from UCSC Genome Browser Database. For precise evaluation, we investigated Spearman correlation between the normalization results from RNA-Seq and MAQC qRT-PCR values for 996 genes. Based on this work, we showed that out of the eight non-abundance estimation normalization methods, RC, UQ, Med, TMM, DESeq, and Q gave similar normalization results for all data sets. For RNA-Seq of a 35-nucleotide sequence, RPKM showed the highest correlation results, but for RNA-Seq of a 76-nucleotide sequence, least correlation was observed than the other methods. ERPKM did not improve results than RPKM. Between two abundance estimation normalization methods, for RNA-Seq of a 35-nucleotide sequence, higher correlation was obtained with Sailfish than that with RSEM, which was better than without using abundance estimation methods. However, for RNA-Seq of a 76-nucleotide sequence, the results achieved by RSEM were similar to without applying abundance estimation methods, and were much better than with Sailfish. Furthermore, we found that adding a poly-A tail increased alignment numbers, but did not improve normalization results.ConclusionSpearman correlation analysis revealed that RC, UQ, Med, TMM, DESeq, and Q did not noticeably improve gene expression normalization, regardless of read length. Other normalization methods were more efficient when alignment accuracy was low; Sailfish with RPKM gave the best normalization results. When alignment accuracy was high, RC was sufficient for gene expression calculation. And we suggest ignoring poly-A tail during differential gene expression analysis.

Combined Hypermethylation of APC and GSTP1 as a Molecular Marker for Prostate Cancer Quantitative Pyrosequencing Analysis

A total of 149 human prostate tissues obtained from our institute were assessed: 52 specimens of benign prostate hyperplasia (BPH) and 97 specimens of prostate cancer (PCa). The methylation status of the genes of Adenomatous polyposis coli (APC) and glutathione-S-transferase-P1 (GSTP1) was analyzed by quantitative pyrosequencing. A methylation score (M score) was calculated to capture the combined methylation level of both genes. The methylation level of each single gene and that of both genes combined was significantly higher in PCa specimens than in BPH (each p < 0.001). The value of APC methylation, GSTP1 methylation, and M score for predicting PCa was measured by the area under the receiver operating characteristic (ROC) curve and reached 0.954, 0.942, and 0.983, respectively. The sensitivity and specificity of the M score in discriminating between PCa and BPH reached 92.8% and 100.0%, respectively. The M score was positively associated with the serum prostate-specific antigen (PSA) level (p trend < 0.001). Our study demonstrates that the quantitative measurement of two methylation markers might drastically improve the ability to discriminate PCa from BPH.

QSE: A new 3-D solvent exposure measure for the analysis of protein structure†

Solvent exposure of amino acids measures how deep residues are buried in tertiary structure of proteins, and hence it provides important information for analyzing and predicting protein structure and functions. Existing methods of calculating solvent exposure such as accessible surface area, relative accessible surface area, residue depth, contact number, and half‐sphere exposure still have some limitations. In this article, we propose a novel solvent exposure measure named quadrant‐sphere exposure (QSE) based on eight quadrants derived from spherical neighborhood. The proposed measure forms a microenvironment around Cα atom as a sphere with a radius of 13 Å, and subdivides it into eight quadrants according to a rectangular coordinate system constructed based on geometric relationships of backbone atoms. The number of neighboring Cα atoms whose labels are the same is given as the QSE value of the center Cα atom at hand. As evidenced by histograms that show very different distributions for different structure configurations, the proposed measure captures local properties that are characteristic for a residues eight‐directional neighborhood within a sphere. Compared with other measures, QSE provides a different view of solvent exposure, and provides information that is specific for different tertiary structure. As the experimental results show, QSE measure can potentially be used in protein structure analysis and predictions.

A New Ensemble Method with Feature Space Partitioning for High-Dimensional Data Classification

Ensemble data mining methods, also known as classifier combination, are often used to improve the performance of classification. Various classifier combination methods such as bagging, boosting, and random forest have been devised and have received considerable attention in the past. However, data dimensionality increases rapidly day by day. Such a trend poses various challenges as these methods are not suitable to directly apply to high-dimensional datasets. In this paper, we propose an ensemble method for classification of high-dimensional data, with each classifier constructed from a different set of features determined by partitioning of redundant features. In our method, the redundancy of features is considered to divide the original feature space. Then, each generated feature subset is trained by a support vector machine, and the results of each classifier are combined by majority voting. The efficiency and effectiveness of our method are demonstrated through comparisons with other ensemble techniques, and the results show that our method outperforms other methods.

IMTAR: Incremental Mining of General Temporal Association Rules

Nowadays due to the rapid advances in the field of information systems, transactional databases are being updated regularly and/or periodically. The knowledge discovered from these databases has to be maintained, and an incremental updating technique needs to be developed for maintaining the discovered association rules from these databases. The concept of Temporal Association Rules has been introduced to solve the problem of handling time series by including time expressions into association rules. In this paper we introduce a novel algorithm for Incremental Mining of General Temporal Association Rules (IMTAR) using an extended TFP-tree. The main benefits introduced by our algorithm are that it offers significant advantages in terms of storage and running time and it can handle the problem of mining general temporal association rules in incremental databases by building TFP-trees incrementally. It can be utilized and applied to real life application domains. We demonstrate our algorithm and its advantages in this paper.

Trigger Learning and ECG Parameter Customization for Remote Cardiac Clinical Care Information System

Coronary heart disease is being identified as the largest single cause of death along the world. The aim of a cardiac clinical information system is to achieve the best possible diagnosis of cardiac arrhythmias by electronic data processing. Cardiac information system that is designed to offer remote monitoring of patient who needed continues follow up is demanding. However, intra- and interpatient electrocardiogram (ECG) morphological descriptors are varying through the time as well as the computational limits pose significant challenges for practical implementations. The former requires that the classification model be adjusted continuously, and the latter requires a reduction in the number and types of ECG features, and thus, the computational burden, necessary to classify different arrhythmias. We propose the use of adaptive learning to automatically train the classifier on up-to-date ECG data, and employ adaptive feature selection to define unique feature subsets pertinent to different types of arrhythmia. Experimental results show that this hybrid technique outperforms conventional approaches and is, therefore, a promising new intelligent diagnostic tool.

Comparison of clinical outcomes between culprit vessel only and multivessel percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel coronary diseases

Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction (STEMI) patients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention (PPCI) were analyzed. We used propensity score matching (PSM) to control differences of baseline characteristics between culprit only intervention (CP) and multivessel percutaneous coronary interventions (MP), and between double vessel disease (DVD) and triple vessel disease (TVD). The major adverse cardiac event (MACE) was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE (14.2% vs. 8.6%, P = 0.01), any cause of revascularization (10.6% vs. 5.9%, P = 0.01), and repeated PCI (9.5% vs. 5.7%, P = 0.02), as compared to DVD patients during one year after discharge. MP reduced MACE effectively (7.3% vs. 13.8%, P = 0.03), as compared to CP for one year, but all cause of death (1.6% vs. 3.2%, P = 0.38), MI (0.4% vs. 0.8%, P = 1.00), and any cause of revascularization (5.3% vs. 9.7%, P = 0.09) were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD. MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.

Superiority real-time cardiac arrhythmias detection using trigger learning method

The Electrocardiogram (ECG) signal uses by Clinicians to extract very useful information about the functional status of the heart, accurate and computationally efficient means of classifying cardiac arrhythmias has been the subject of considerable research efforts in recent years. The contradicting considerations on the unique characteristics of patients activities and the inherent requirements of real-time heart monitoring pose challenges for practical implementation. That is due to susceptibility to potentially changing morphology not only between different patients or patient cluster, but also within the same patient. As a result, the model constructed using an old training data no longer needs to be adapt with the new concepts. Consequently, developing one classifier model to satisfy all patients in different situation using static training datasets is unsuccessful. Our proposed methodology automatically trains the classifier model by up-to-date training data, so as to be identifying with the new concepts. The performance of the trigger method is evaluated using various approaches. The results demonstrate the effectiveness of our proposed technique, and they suggest that it can be used to enhance the performance of new intelligent assistance diagnosis systems.

Proposal reviewer recommendation system based on big data for a national research management institute

National research management organizations need to ensure that research proposals are reviewed fairly and efficiently, which requires the selection of suitable reviewers. In particular, reviewing research proposals in a particular area necessitates the selection of a group with the most reasonable standard for recommending an expert in that area. In this study, we develop an automatic matching system that matches a research proposal with a reviewer who can evaluate it most effectively, using keywords with fuzzy weights based on databases in the corresponding field of research. All functions that we developed were based on the MapReduce framework created by Hadoop, which was verified to enhance matching performance and ensure expandability. This enabled us to select suitable researchers from existing research projects, papers and research reviewer databases. Our system can influence the operation of the national research management system and contribute to academic development.

Evolutional Diagnostic Rules Mining for Heart Disease Classification Using ECG Signal Data

Medical information related data sets are useful for the diagnosis and treatment of disease. With the development of technology and devices in biomedical engineering, it leads data overflow nowadays. Traditional data mining methods like SVM, ANN and decision tree are applied to perform the classification of arrhythmia disease. However, traditional analysis methods are far beyond the capacity and speed to deal with large scale of information. Techniques that have capability to handle the coming data sets in incremental learning phase can solve those problems. Therefore, in this paper, we proposed an incremental decision trees induction method which uses ensemble method for mining evolutional diagnostic rules for cardiac arrhythmia classification. Experimental results show that our proposed method performs better than other algorithms in our study.