• Genomics & Informatics
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• 제12권4호
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• pp.145-150
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• 2014

Recent technical advances, such as chromatin immunoprecipitation combined with DNA microarrays (ChIp-chip) and chromatin immunoprecipitation-sequencing (ChIP-seq), have generated large quantities of high-throughput data. Considering that epigenomic datasets are arranged over chromosomes, their analysis must account for spatial or temporal characteristics. In that sense, simple clustering or classification methodologies are inadequate for the analysis of multi-track ChIP-chip or ChIP-seq data. Approaches that are based on hidden Markov models (HMMs) can integrate dependencies between directly adjacent measurements in the genome. Here, we review three HMM-based studies that have contributed to epigenetic research, from a computational perspective. We also give a brief tutorial on HMM modelling-targeted at bioinformaticians who are new to the field.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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• pp.45-52
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• 2000

Genomic approach produces massive amount of data within a short time period, New high-throughput automatic sequencers can generate over a million nucleotide sequence information overnight. A typical DNA chip experiment produces tens of thousands expression information, not to mention the tens of megabyte image files, These data must be handled automatically by computer and stored in electronic database, Thus there is a need for systematic approach of data collection, processing, and analysis. DNA sequence information is translated into amino acid sequence and is analyzed for key motif related to its biological and/or biochemical function. Functional genomics will play a significant role in identifying novel drug targets and diagnostic markers for serious diseases. As an enabling technology for functional genomics, bioinformatics is in great need worldwide, In Korea, a new functional genomics project has been recently launched and it focuses on identi☞ing genes associated with cancers prevalent in Korea, namely gastric and hepatic cancers, This involves gene discovery by high throughput sequencing of cancer cDNA libraries, gene expression profiling by DNA microarray and proteomics, and SNP profiling in Korea patient population, Our bioinformatics team will support all these activities by collecting, processing and analyzing these data.

• Journal of Microbiology and Biotechnology
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• 제24권8호
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• pp.1143-1147
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• 2014

Human papillomavirus (HPV) infection is considered to play a critical role in the development of cervical carcinoma, which is the third most common cancer among Korean females. Here, we performed a baseline study of HPV infection and genotyping using an HPV DNA chip, which is a type of oligonucleotide microarray. A total of 6,855 cervical swab specimens from 5,494 women attending Dankook University Hospital Health Improvement Center in Cheonan, Korea between 2006 and 2012, originally collected for HPV infection screening, were genotyped for HPV. The extracted DNA from the cervical specimens was investigated by an HPV DNA chip designed to detect 41 different HPV types. HPV was identified as positive in 1,143 (16.7%) of the 6,855 samples. The most frequently detected HPV genotypes were HPV types 16, 53, 56, 58, 39, 52, 70, 84, 68, 62, 35, 54, 81, 18, and 30, in descending order of incidence. The proportions of single and multiple HPV infections in the HPV-positive specimens were 78.1% and 21.9%, respectively. The average age of HPV-positive patients was 39.9 years, with the positive rate of HPV being the highest in the 10-29 age group (20.6%). We report here on the prevalence and distribution of 41 different genotypes of HPV according to age among women in Cheonan, Korea. These data may be of use as baseline data for the assessment of public health-related issues and for the development of area-specific HPV vaccines.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2001년도 제2회 생물정보 워크샵 (DNA Chip Bioinformatics)
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• pp.165-196
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• 2001

DNA chip 또는 microarray는 다수의 유전자 또는 유전자 조각을 (보통 수천내지 수만 개)칩상에 고정시켜 놓고 DNA hybridization 반응을 이용하여 유전자들의 발현 양상을 분석할 수 있는 기술이다. 이러한 high-throughput기술은 예전에는 생각하지 못했던 여러가지 분자생물학의 문제에 대한 해답을 제시해 줄 수 있을 뿐 만 아니라, 분자수준에서의 질병 진단, 신약 개발, 환경 오염 문제의 해결 등 그 응용 가능성이 무한하다. 이 기술의 실용적인 적용을 위해서는 DNA chip을 제작하기 위한 하드웨어/웻웨어 기술 외에도 이러한 데이터로부터 최대한 유용하고 새로운 지식을 창출하기 위한 bioinformatics 기술이 핵심이라고 할 수 있다. 유전자 발현 패턴을 데이터마이닝하는 문제는 크게 clustering, classification, dependency analysis로 구분할 수 있으며 이러한 기술은 통계학과인공지능 기계학습에 기반을 두고 있다. 주로 사용된 기법으로는 principal component analysis, hierarchical clustering, k-means, self-organizing maps, decision trees, multilayer perceptron neural networks, association rules 등이다. 본 세미나에서는 이러한 기본적인 기계학습 기술 외에 최근에 연구되고 있는 새로운 학습 기술로서 probabilistic graphical model (PGM)을 소개하고 이를 DNA chip 데이터 분석에 응용하는 연구를 살펴본다. PGM은 인공신경망, 그래프 이론, 확률 이론이 결합되어 형성된 기계학습 모델로서 인간 두뇌의 기억과 학습 기작에 기반을 두고 있으며 다른 기계학습 모델과의 큰 차이점 중의 하나는 generative model이라는 것이다. 즉 일단 모델이 만들어지면 이것으로부터 새로운 데이터를 생성할 수 있는 능력이 있어서, 만들어진 모델을 검증하고 이로부터 새로운 사실을 추론해 낼 수 있어 biological data mining 문제에서와 같이 새로운 지식을 발견하는 exploratory analysis에 적합하다. 또한probabilistic graphical model은 기존의 신경망 모델과는 달리 deterministic한의사결정이 아니라 확률에 기반한 soft inference를 하고 학습된 모델로부터 관련된 요인들간의 인과관계(causal relationship) 또는 상호의존관계(dependency)를 분석하기에 적합한 장점이 있다. 군체적인 PGM 모델의 예로서, Bayesian network, nonnegative matrix factorization (NMF), generative topographic mapping (GTM)의 구조와 학습 및 추론알고리즘을소개하고 이를 DNA칩 데이터 분석 평가 대회인 CAMDA-2000과 CAMDA-2001에서 사용된cancer diagnosis 문제와 gene-drug dependency analysis 문제에 적용한 결과를 살펴본다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1687-1689
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• 2013

We performed a case-control study to investigate whether SNPs of CHIP might affect the development of IA in Chinese Han nationality. We believe we are the first to have screened IA patients for mutations in the CHIP gene to determine the association with these variants. The study group comprised 224 Chinese Han nationality patients with at least one intracranial aneurysm and 238 unrelated healthy Han nationality controls. Genomic DNA was isolated from blood leukocytes. The entire coding regions of CHIP were genotyped by PCR amplification and DNA sequencing. Differences in genotype and allele frequencies between patients and controls were tested by the chi-square method. Genotype and allele frequencies of the SNP rs116166850 was demonstrated to be in Hardy-Weinberg equilibrium. No significant difference in genotype or allele frequencies between case and control groups was detected at the SNP. Our data do not support the hypothesis of a major role for the CHIP gene in IA development in the Chinese Han population.

• 한국미생물·생명공학회지
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• 제38권1호
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• pp.70-76
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• 2010

The single-stranded large circular (LC)-sense DNA were utilized as probes for DNA chip experiments. The microarray experiment using LC-sense DNA probes found differentially expressed genes in A549 cells as compared to WI38VA13 cells, and microarray data were well-correlated with data acquired from quantitative real-time RT-PCR. A 5K LC-sense DNA microarray was prepared, and the repeated experiments and dye swap test showed consistent expression patterns. Subsequent functional analysis using LC-antisense library of overexpressed genes identified several genes involved in A549 cell growth. These experiments demonstrated proper feature of LC-sense molecules as probe DNA for microarray and the potential utility of the combination of LC-sense microarray and antisense libraries for an effective functional validation of genes.

• Genomics & Informatics
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• 제1권2호
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• pp.94-100
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• 2003

Motivation: Many have observed a nonlinear relationship between the signal intensity and the transcript abundance in microarray data. The first step in analyzing the data is to normalize it properly, and this should include a correction for the nonlinearity. The commonly used linear normalization schemes do not address this problem. Results: Nonlinearity is present in both cDNA and oligonucleotide arrays, but we concentrate on the latter in this paper. Across a set of chips, we identify those genes whose within-chip ranks are relatively constant compared to other genes of similar intensity. For each gene, we compute the sum of the squares of the differences in its within-chip ranks between every pair of chips as our statistic and we select a small fraction of the genes with the minimal changes in ranks at each intensity level. These genes are most likely to be non-differentially expressed and are subsequently used in the normalization procedure. This method is a generalization of the rank-invariant normalization (Li and Wong, 2001), using all available chips rather than two at a time to gather more information, while using the chip that is least likely to be affected by nonlinear effects as the reference chip. The assumption in our method is that there are at least a small number of non­differentially expressed genes across the intensity range. The normalized expression values can be substantially different from the unnormalized values and may result in altered down-stream analysis.

• 한국정보과학회논문지:소프트웨어및응용
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• 제29권11호
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• pp.775-784
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• 2002

DNA chip 기술에 의해 얻어지는 마이크로어레이(microarray) 데이타는 세포나 조직 내의 수천 개 유전자의 발현도(expression level)를 한번에 측정한 것으로, 유전자 발현 양상에 기반한 암의 진단, 유전자의 기능 예측 등에 이용되고 있다. 다양한 데이타 분석 기법들 중 베이지안망(Bayesian network)은 데이타의 각 속성들간의 관계를 그래프 형태로 표현할 수 있는 특징을 가지고 있다. 이는 마이크로어레이 데이타의 분석을 통해 여러 유전자와 조직의 특성(암의 종류 등) 사이의 관계를 밝히는데 유용하다 하지만 대부분의 마이크로어레이 데이타는 sparse data로 베이지안망을 비롯한 각종 분석 기법의 적용을 어렵게 하고 있다. 본 논문에서는 베이지안망에 기반한 마이크로어레이 데이타 분석을 위해 효율적 구조 학습 알고리즘과 데이타 차원 축소를 이용한다. 제시되는 분석법은 실제 마이크로어레이 데이타인 NC160 data set에 적용되었으며, 그 유용성은 데이타로부터 학습된 베이지안망이 실제 생물학적으로 알려진 사실들을 어느 정도 정확하게 표현하는지에 의해 평가되었다.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2003년도 ICCAS
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• pp.2226-2229
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• 2003

A new method is presented to construct a classifier. This was accomplished by combining a generalized regression neural network (GRNN) and a genetic algorithm (GA). The classifier constructed in this way is referred to as a GA-GRNN. The GA played a role of controlling training factors simultaneously. In GA optimization, neuron spreads were represented in a chromosome. The proposed optimization method was applied to a data set, consisted of 4 different promoter sequences. The training and test data were composed of 115 and 58 sequence patterns, respectively. The range of neuron spreads was experimentally varied from 0.4 to 1.4 with an increment of 0.1. The GA-GRNN was compared to a conventional GRNN. The classifier performance was investigated in terms of the classification sensitivity and prediction accuracy. The GA-GRNN significantly improved the total classification sensitivity compared to the conventional GRNN. Also, the GA-GRNN demonstrated an improvement of about 10.1% in the total prediction accuracy. As a result, the proposed GA-GRNN illustrated improved classification sensitivity and prediction accuracy over the conventional GRNN.

• Genomics & Informatics
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• 제5권2호
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• pp.83-87
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• 2007

The analysis of DNA microarray data is a rapidly evolving area of bioinformatics, and various types of microarray are emerging as some of the most exciting technologies for use in biological and clinical research. In recent years, microarray technology has been utilized in various applications such as the profiling of mRNAs, assessment of DNA copy number, genotyping, and detection of methylated sequences. However, the analysis of these heterogeneous microarray platform experiments does not need to be performed separately. Rather, these platforms can be co-analyzed in combination, for cross-validation. There are a number of separate laboratory information management systems (LIMS) that individually address some of the needs for each platform. However, to our knowledge there are no unified LIMS systems capable of organizing all of the information regarding multi-platform microarray experiments, while additionally integrating this information with tools to perform the analysis. In order to address these requirements, we developed a web-based LIMS system that provides an integrated framework for storing and analyzing microarray information generated by the various platforms. This system enables an easy integration of modules that transform, analyze and/or visualize multi-platform microarray data.