지식기반 유전자알고리즘을 이용한 한국인 빈발 HLA 대립유전자에 대한 결합 펩타이드 예측

조연진 ( Yeon-jin Cho ),오흥범 ( Heung-bum Oh ),김현철 ( Hyeoncheol Kim ) 한국인터넷정보학회 2012 인터넷정보학회논문지 Vol.13 No.4

감염된 미생물에서 유래한 단백질 펩타이드가 HLA에 결합하여 숙주의 세포표면에 제시되면, T 세포가 이를 인식하여 면역반응을 유발함으로써 감염원을 제거하게 된다. HLA와 펩타이드간의 결합이 안정적일수록 T 세포반응이 강하게 일어나 효율적으로 감염원을 제거할 수 있다고 알려져 있다. 따라서 특정 HLA에 안정적으로 결합할 수 있는 펩타이드(HLA binder)를 찾아낼 수 있다면 감염질환이나 암의 예방을 위한 펩타이드 백신의 개발에 활용될 수 있다. 그런데 HLA는 매우 다형하기 때문에 하나의 집단 내에서도 어느 정도의 빈도를 가지는 대립유전자의 수가 매우 많다. 따라서 이들 모든 대립유전자들에 대해 가능한 펩타이드조합을 제작한 후 직접 실험을 통해 안정적으로 결합하는 펩타이드를 찾아내는 것은 매우 비효율적이다. 이를 극복하기 위하여 특정 HLA에 안정적으로 결합하는 펩타이드를 예측하는 정보전산적인 방법이 최근 개발되어 왔다. 이들 방법을 통해 제시된 펩타이드에 대해서만 직접 생물학적 실험을 시행함으로써 연구자는 검증해야 할 후보 펩타이드의 수를 현격히 감소시킬 수 있게 된다. 본 논문에서는 HLA 결합 펩타이드 예측을 위해 기계학습을 이용한 방법을 소개할 뿐만 아니라, 지금까지 HLA 결합 펩타이드 예측에 시도된 적이 없는 `지식기반 유전자알고리즘(knowledge-based genetic algorithm)`이라는 새로운 모델을 제시하고자 한다. 이것은 유전자알고리즘(GA)에 기반한 것이었지만 전문가 지식을 접목함으로써 GA보다 더 향상된 성능으로 한국인에 흔한 HLA에 결합하는 펩타이드를 예측하였다. 뿐만 아니라 이것은 결합하는 펩타이드의 규칙을 한국인에 흔한 HLA 대립유전자에 대하여 추출해 줄 수 있는 새로운 방법이었다. T cells induce immune responses and thereby eliminate infected micro-organisms when peptides from the microbial proteins are bound to HLAs in the host cell surfaces, It is known that the more stable the binding of peptide to HLA is, the stronger the T cell response gets to remove more effectively the source of infection. Accordingly, if peptides (HLA binder) which can be bound stably to a certain HLA are found, those peptieds are utilized to the development of peptide vaccine to prevent infectious diseases or even to cancer. However, HLA is highly polymorphic so that HLA has a large number of alleles with some frequencies even in one population. Therefore, it is very inefficient to find the peptides stably bound to a number of HLAs by testing random possible peptides for all the various alleles frequent in the population. In order to solve this problem, computational methods have recently been developed to predict peptides which are stably bound to a certain HLA. These methods could markedly decrease the number of candidate peptides to be examined by biological experiments. Accordingly, this paper not only introduces a method of machine learning to predict peptides binding to an HLA, but also suggests a new prediction model so called `knowledge-based genetic algorithm` that has never been tried for HLA binding peptide prediction. Although based on genetic algorithm (GA). it showed more enhanced performance than GA by incorporating expert knowledge in the process of the algorithm. Furthermore, it could extract rules predicting the binding peptide of the HLA alleles common in Koreans.

원저(原著) : 성분채집기에 따른 성분채집혈장의 유리혈색소량

조영희 ( Young Hee Cho ),한희숙 ( Hee Sook Han ),오흥범 ( Heung Bum Oh ) 대한임상병리사협회 1997 임상수혈검사학회 발표자료집 Vol.4 No.1

In order to satisfy the self-sufficiency of plasma, the Korean Red Cross has opened many blood donation offices, where many apheresis machines have been installed for plasmapheresis. It is very important for the donors to feel comfortable on plasmaphersis because they may donate frequently. Plasma hemoglobin can cause problem to both donors and patients. In this study, plasma hemoglobin was compared between pheresis machines (Fenwal Autopheresis C system vs Fenwal Autopheresis C system mini instrument vs Haemonetics Mobile collection system vs Haemonetics Plasma collection system). Plasma hemoglobin in FFP was also measured. Amount (Mean ± SD) of plasma hemoglobin by Auto-C and Mini Auto-C of Fenwal`s was 2.87 mg/dL ± 2.02 mg/dL and 3.86 mg/dl ± 2.77 mg/dL respectively. And that of PCS and MCS was 2.86 mg/dL ± 1.56 mg/dL and 1.94 mg/dL ± 2.58 mg/dL respectively. There was no statistically significant difference between machines of the same companies. However amount of free hemoglobin was lower in plasma collected by Haemonetics (p=0.013) even though amount of free hemoglobin generated by each machines of both companies was with in the normal range of human plasma hemoglobin. Amount of free hemoglobin in FFP was in the middle between that of Fenwal`s and Haemonetics`. High level of free hemoglobin by Fenwal`s is thought to be caused by membrane filter that is installed to prevent red cell contamination from plasma. This results dosen`t mean that red cell itself is more contaminated in Fenwal`s. Considering that amount of free hemoglobin in all the plasma was within the normal range, it can be concluded that all the machines tested in this study can be used doesn`t cause any problem occured by free hemoglobin.

The 1st Interasma Conference , North Asia / Korea Chapter : Reciprocal genetic predisposition between atopy and rheumatoid arthritis

민경업(Kyung Up Min),김윤근(Yoon Keun Kim),오흥범(Heung Bum Oh),(Sun Young Oh),조상헌(Sang Heon Cho),김유영(You Young Kim) 대한천식 및 알레르기학회 ( 구 대한알레르기학회 ) 2000 The 1st Interasma Conference, North Asia / Korea C Vol.- No.-

효소면역검사법상 EBV VCA IgM 양성 결과를 보안 예들에 의한 ImmunoDot 추가검사 및 염상상 고찰을 통한 효용성 검토

김봉철 ( Bong Cheol Kim ),황상현 ( Sang Hyun Hwang ),오흥범 ( Heung Bum Oh ) 대한임상검사과학회 2001 대한임상검사과학회지(KJCLS) Vol.33 No.2

Background : Serologic testing is the method of choice for the diagnosis of Epstein-Barr virus(EBV) infection. Effective laboratory diagnosis is generally made using sample by measuring antibodies to a panel of EBV -associated antigens by enzyme immunoassay. However, antibodies are usually acquired earlier in life. πlerefore, it is highly recommended that positive results of VCA IgM in adult be retested by other methods. Methods A total of 851 samples were tested for EBV antibody panel by EIA(EBVVCA IgM ELISA, IBL Hamburg, Germany). Positive samples were retESted by ImmunoDot (GenBio, CA, USA) and clinical review for those patients was done. Result 26 of 851(3.1 %) sample were VCA IgM positive by EIA. However, 25 samples showed negative reaction by ImmunoDot test. No clinical sympyoms were noted for 20 patient who were in pre- or post-transplantation state. EBV panel tests were one of routine protocol for transplantation in our hospital. another 5 cases were to have suffered 잠om FUO (8 years) , cervical lymphadenopathy(5 years), SLE(36 years), adult onset still‘s disease(36 years) , and elevated liver enzyme during the treatment of of medulloblastoma(l2 ye따s). these patient were not finally recorded to have EBV infection. clinical presentation of only one case(27 years), who showed positive reaction in both EIA and ImmunoDot, was compatible with EBV infection, in whom fever, cervical lymphadenopathy, acute pharyngitis and splenomegaly, elevated ASTjALT(21lj644 IUjL), and atypical lymphocytosis(29%) were noted. only this patient was chated to be diagnosed as infectious mononucleosis by EBV. Conclusion : We concluded that supplemental test for EBV VCA IgM by ImmunoDot (Genbio, CA, USA) was useful. Considering that most Koreans are infected with EBV earlier in life, supplemental test by other methods is to be necessary in cases showing VCA IgM positivity in Korea.

β2 아드레날린 수용체 유전자다형과 기관지천식 표현형과의 연관성

손성욱(Sung Wook Sohn),장윤석(Yoon Seok Chang),김상훈(Sang Hoon Kim),오선영(Sun Young Oh),오흥범(Heung Bum Oh),김윤근(Yoon Keun Kim),조상헌(Sang Heon Cho),민경업(Kyung Up Mim),김유영(You Young Kim),최병휘(Byung Whoi Choi) 대한천식알레르기학회 2001 천식 및 알레르기 Vol.21 No.6

N/A N/A

효과적인 HLA개체인식을 위한 부분매칭기법

채정민 ( Jeong Min Chae ),정영희 ( Young Hee Jung ),이태민 ( Tae Min Lee ),채지은 ( Ji Eun Chae ),오흥범 ( Heung Bum Oh ),정순영 ( Soon Young Jung ) 한국컴퓨터교육학회 2011 컴퓨터교육학회 논문지 Vol.14 No.2

생의학분야에서 문헌에 표기된 개체를 인식하기 위해 길이우선매칭기법을 빈번히 사용한다. 길이우선매칭기법은 사전을 이용한 개체인식기법으로 좋은 사전만 구축되어 있다면 빠르고 정확하게 개체를 찾아낼 수 있다는 장점을 가진다. 그러나 개체가 나열되고 중복된 단어가 생략될 경우에는 길이우선매칭기법을 이용할 경우 성능이 현저히 떨어지게 된다. 우리는 이러한 인식성능문제를 해결하기 위해 부분매칭기법을 제안한다. 제안된 부분매칭기법은 생략이 발생될 수 있다는 것을 가정하여 다수의 후보개체를 만들어 내고 그 후에 최적화 알고리즘을 통해 다수의 개체후보 중에서 가장 타당해 보이는 개체를 선택한다. 우리는 생의학분야의 개체 중에서 나열되는 경우가 빈번한 HLA 유전자, HLA 항원, HLA 대립유전자 개체들을 대상으로 길이우선매칭기법과 제안된 부분매칭기법의 개체인식성능을 분석하였다. 3종의 HLA 개체들을 인식하기 위해서 먼저 확장사전과 태그기반사전을 구축하였으며, 그 후 구축된 사전을 이용해 길이우선매칭과 부분매칭을 수행하였다. 실험결과에 따르면 길이우선매칭기법은 HLA 항원 개체에서 좋은 성능을 보였으며 부분매칭기법은 생략된 표현이 빈번한 HLA 유전자 개체, HLA 대립유전자 개체에서 좋은 성능을 보였다. 부분매칭기법은 HLA 대립유전자 개체를 대상으로 95.59%의 높은 F-score를 얻었다. In the biomedical domain, the longest matching method is frequently used for recognizing named entity written in the literature. This method uses a dictionary as a resource for named entity recognition. If there exist appropriated dictionary about target domain, the longest matching method has the advantage of being able to recognize the entities of target domain quickly and exactly. However, the longest matching method is difficult to recognize the enumerated named entities, because these entities are frequently expressed as being omitted some words. In order to resolve this problem, we propose the partial matching method using a dictionary. The proposed method makes several candidate entities on the assumption that the ellipses may be included. After that, the method selects the most valid one among candidate entities through the optimization algorithm. We tested the longest and partial matching method about HLA entities: HLA gene, antigen, and allele entities, which are frequently enumerated among biomedical entities. As preparing for named entity recognition, we built two new resource, extended dictionary and tag-based dictionary about HLA entities. And later, we performed the longest and partial matching method using each dictionary. According to our experiment result, the longest matching method was effective in recognizing HLA antigen entities, in which the ellipses are rare, and the partial matching method was effective in recognizing HLA gene and allele entities, in which the ellipses are frequent. Especially, the partial matching method had a high F-score 95.59% about HLA alleles.

한국 소아에서 알레르기 질환의 선별검사로서 Phadiatop(R)Infant 검사법의 임상적 유용성

김병주 ( Byoung Ju Kim ),이정용 ( Jung Yong Lee ),송영화 ( Young Hwa Song ),유진호 ( Jin Ho Yu ),오흥범 ( Heung Bum Oh ),홍수종 ( Soo Jong Hong ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2009 소아알레르기 및 호흡기학회지 Vol.19 No.2

목적: 아토피(IgE sensitization)는 IgE-매개성 알레르기질환 발생의 위험인자일 뿐 아니라 향후 예후에 대한 가장 중요한 인자이다. Phadiatop(R)Infant는 소아에서 감작률이 높은 항원으로 구성된 복합항원으로 ImmunoCAP을 측정하며 결과는 양성 및 음성으로 보고되어 IgE-매개성 알레르기 질환이 의심되는 소아에서 사용할 수 있는 선별검사이다. 본 연구에서는 한국 소아에서 흔한 식품 및 흡입항원에 대한 특이 IgE 유무를 검출하데 있어 PhadiatopInfant 검사법의 유용성을 알아보고자 하였다. 방법: 2008년 1월부터 2008년 7월까지 아토피피부염 혹은 반복천명을 주소로 서울아산병원 소아천식 아토피센터를 방문한 소아들을 대상으로 Phadiatop Infant 검사를 시행하고 동시에 6가지 흡입항원(D.p, D.f, cat, dong, cockroach, alternaria) 및 6가지 식품항원(egg, milk, soybean, wheat, fish, peanut)에 대한 특이 IgE 항체를 측정하여 두 가지 검사법에 대한 일치율 및 IgE-매개성 알레르기 질환의 진단에 있어 Phadiatop(R)Infant 검사법의 유용성을 조사하였다. 결과: 총 93명의 소아가 본 연구에 참여하였으며 이중 남자는 54명 여자는 39명이었다. 평균나이는 32.4(±20.4)개월이었다. 특이항원 측정에 의한 흡입항원에 감작률은 38.7%, 식품항원에 감작률은 53.8%, 12가지 항원 중 하나이상의 감작률은 71%였다. Phadiatop(R)Infant에 의한 양성률은 66.9%였다. 적어도 하나 이상의 특이항원에 대한 감작유무와 Phadiatop(R)Infant 검사의 일치도는 0.768(Kappa value)이었다. Phadiatop(R)Infant에 양성이나 특이항원이 검출되지 않은 경우가 4례, Phadiatop(R)Infant에 음성이나 특이항원이 검출된 경우는 5례이었으며 후자에서는 모두 집먼지진드기 특이항원이 검출되었으며 전자에서는 1례를 제외하고 연령이 36개월 이상이었다. 나이별에 따른 일치율은 나이가 적을수록 높은 경향을 보였다. κ=0.933(0-24개월), 0.692(25-48개월), 0.619(49개월 이상) 결론: Phadiatop(R)Infant 검사는 한국 소아에서 IgE-매개성 질환을 진단하는데 유용하며 특히 나이가 어릴수록 유용할 것으로 생각된다. 이는 어릴수록 식품항원에 대한 감작이 높으며 연령이 높아질수록 흡입항원에 대한 감작이 증가하기 때문으로 사료된다. Purpose: Atopy is a prerequisite for IgE-mediated allergic disease and also a significant prognostic factor. Phadiatop(R)Infant (phadia AB, uppsala, sweden) is a new blood test designed for the detecting the presence of IgE sensitization in young children. This study aims to investigate the usefulness of Phadiatop(R)Infant test in Korea. Methods: Among the patients who visited Childhood Asthma Atopy Center, Asan Medical Center between January 2008 and August 2008, young children under 6 years of age who had eczema or wheezing were enrolled. Ninety-three patients were tested using specific IgE antibody tests with 6 aeroallergen including Dermatophagoides pteronyssinus (D.p), Dermatophagoides farinae (D.f), cat, dog, cockroach and alternaria, and 6 food allergen including egg, milk, soybean, wheat, fish and peanut as well as Phadiatop(R)Infant test. Results: The study group was consisted of 54 males and 39 females, with a mean age of 32.4±20.4 months. By specific IgE antibody test, 38.7% were sensitized to aeroallergen, 53.8% to food allergen, 71% to at least one allergen. Positive rate of Phadiatop(R)Infant was 66.9%. There were 9 discrepant cases: 4 cases with positive Phadiatop(R)Infant but negative specific IgE antibody test and 5 cases with negative Phadiatop(R)Infant but positive specific IgE antibody test. The former cases except one were older than 36 months and all the latter cases were sensitized to house dust mite. The kappa value between Phadiatop(R)Infant and specific IgE antibody test was 0.768. When the age was considered, the younger children showed the better agreement rate [kappa value=0.933 (<24 months), 0.692 (24-48 months) and 0.619 (>48 months)]. Conclusion: Phadiatop(R)Infant may be a useful screening test for atopy in Korean children, especially in younger children. It is presumed that the rates of sensitization to local inhalant allergen become higher with increasing age. [Pediatr Allergy Respir Dis(Korea) 2009;19:155-164]

비정형 림프구증가증과 만성 Epstein-Barr virus 감염을 동반한 모기 침산 과민반응 1례

박소연 ( So Yeon Park ),조유숙 ( You Sook Cho ),김성호 ( Seung Ho Kim ),이창근 ( Chang Keun Lee ),유빈 ( Bin Yoo ),김상위 ( Sang Wi Kim ),오흥범 ( Heung Bum Oh ),박찬정 ( Chan Jeoung Park ),문희범 ( Hee Bom Moon ) 대한천식알레르기학회 2003 천식 및 알레르기 Vol.23 No.2

Hypersensitivity to mosquito bites is a disorder characterized by necrotic skin reactions and systemic generalized symptoms subsequent to mosquito bites. This disease has been reported mostly in Japanese patients in their first two decades of life. Recent

귤응애에 대한 감작과 HLA - DRB1 대립유전자와 연관성

이재영(Jae Young Lee),손성욱(Sung Wook Sohn),정재원(Jae Won Jeong),장윤석(Yoon Seok Chang),김상훈(Sang Hoon Kim),오선영(Sun Young Oh),오흥범(Heung Bum Oh),이명현(Myung Hyun Lee),김윤근(Yoon Keun Kim),조상헌(Sang Heon Cho),민경업(Kyun 대한천식알레르기학회 2001 천식 및 알레르기 Vol.21 No.5

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서울중앙병원에서 시행된 항핵항체와 가용성 향원 겸샤 결과의 비교 분석

한태진 ( Tae Jin Han ),조영욱 ( Young Uk Cho ),김봉철 ( Bong Cheol Kim ),조병철 ( Byung Chul Cho ),정윤영 ( Yoon Young Chung ),오흥범 ( Heung Bum Oh ) 대한임상검사과학회 1999 대한임상검사과학회지(KJCLS) Vol.31 No.2

Background : Antinuclear antibodies(ANA) have high sensitivity for the diagnosis of systemic rheumatologic diseases, but have low specificiη relatively. Recently, we have used antibodies to extractable nuclear antigens(ENA) additiona11y, which enabled us to determine what the ANA detected rea11y were. The purpose of this study was to examine frequencies of autoantibodies and clinica1 significances of them by ana1yzing resu1ts of ANA, anti-ENA and anti-dsDNA tests. Methods: From Januaη, 1997 to March, 1998, the sera of 339 patients who were suspected that they have systemic rheumatologic diseases and 54 ones diagnozed as systemic lupus eηthematosus(SLE) were ana1yzed by performing ANA, anti-ENA(anti-RNAjSm, anti-SS - AjS S-B, anti-Sc170) and anti-dsDNA tests. Results : In 339 patients with suspicious systemic rheumatologic diseases, the concordance rate of positivity between ANA and anti-ENA was 23.6% and that of negativiη was 23.3%. The positivity rate of anti-ENA among patients with negative ANA was 0.9%. We detected anti-SS - AjRo in the rate of 41.0%, anti-RNP 16.9%, anti-Sm 2.4%, anti-SS - BjLa 1.2% and anti-Sc170 14.5% among patients with positive anti-ENA. Among 42 patients with positive anti-dsDNA, there were 32 cases with positive anti-ENA. 17 patients had anti-SS - AjRo, 4 ones anti-Scl70, 3 ones anti-RNPjSm. In 54 patients with SLE, the concordance rate of positivity between ANA and either anti-ENA or anti-dsDNA was 72.2%. Among patients with either positive anti-ENA or positive anti-dsDNA, we detected anti-SS - AjRo in the rate of 12.5%, anti-SS - Aj dsDNA 32.5% and anti-dsDNA 17.5%. Conclusion : When the titer of ANA is above 1: 160 and anti-ENA is negative, the accurate identification of ANA specificity would be essentia1 by using enzyme immunoassay or immunoblotting methods. The 1.9% positivity of anti-ENA among ANA negative SLE patients suggests the possibi1ity of presence of ANA-negative SLE in spite of performing ANA test using HEp-2 cells.