서울대학교 생물정보연구소와 생물정보학 협동과정 공동 주최로 특별 세미나를 아래와 같이 열고자 하오니, 많은 참여 바랍니다.

일시: 2015년 9월 30일 수요일 오전 11시

연사: 박정선 (sk 텔레콤)

장소: 서울대학교 25동 411호

Title: The feasibility test of fetal fraction estimation in targeted sequencing using fragment size in the case of Duchenne Muscular Dystrophy (DMD)

Background:

In noninvasive prenatal testing (NIPT), targeted deep sequencing is used to detect micro insertion and deletion for screening Mendelian disorders. In this study, fetal fraction estimation method based on DNA fragment size was applied to targeted sequencing data. The feasibility of DNA fragment size based fetal fraction estimation was already shown in whole genome shallow sequencing (Stephanie Yu et. al). From the comparison of other conventional methods, DNA fragment size based method shows comparable results. Thus, DNA fragment size based method is more cost effective and can be applied for quality control of data. This method works well without any extra gene information and SNP information.

Method:

Custom targeted panel (Agilent SureSelect) was designed to cover the entire DMD gene region. Targeted sequencing was performed using 9 maternal plasma DNA samples at varying gestational weeks from 5 mothers. Fetal genomic DNA obtained from either chorionic villi sampling or amniocentesis and genomic DNA from 5 mothers was used to validate the results. Using mean read depth of two Zinc Finger genes with a minimum mapping quality score of 20 and base quality score of 20, the fractional fetal DNA concentration was calculated as previous study (S. Yoo et. al). Also a size ratio indicating the relative proportions of short and long DNA fragments was calculated for each sample for the comparison of Zinc Finger method (Stephanie Yu et. al.).For more information, we compare the AB allele frequency ratio of hetero SNP sites of mother to confirm the fetal DNA was shorter than maternal DNA. Linear regression was used to compare two methods.

Results:

From the comparison of AB allele frequency ratio based fetal fraction estimation and size ratio based one, the proposed method shows positive correlation (r=0.85, p=3.896x10-8). Similar result is also obtained from the comparison of Zinc Finger based estimation (r=0.67, p=0.09). In addition, our linear model is similar to the previously published whole genome sequencing data (Stephanie C. Y. Yu et. al). Thus fragment size based fetal fraction estimation can be extendible to targeted sequencing.

Reference:

Stephanie C. Y. Yu et. al. Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing. PNAS 111:23 p8583–8588 (2014)Seong-Keun Yoo et. al. Noninvasive Prenatal Diagnosis of Duchenne Muscular Dystrophy: Comprehensive Genetic Diagnosis in Carrier, Proband, and Fetus. Clinical Chemistry 61:6 (2015).

Education:

2007.3 – 2012.2 Ph.D., Interdisciplinary Program in Bioinformatics

Seoul National University, Korea

2001.3 – 2003.2 M.S., Department of Information on Technology

Handong University, Korea

1997.3 – 2001.2 B.S., Department of Life and Food Science

Handong University, Korea

Job Experience:

Manager

Molecular Diagnostics Team.

IVD Business Unit

SK Telecom 2015. 1 - present

Manager

Bioinformatics Tech. Lab.

Healthcare Group

SK Telecom 2011. 9 – 2014.12

Recent Publication:

1. Changsik Kim, Jiwon Choi, Hyunjin Park, Yunsun Park, Jungsun Park, Taesung

Park, Kwanghui Cho, Young Yang and Sukjoon Yoon (2010) Global analysis of

microarray data reveals intrinsic properties in gene expression and tissue

selectivity. Bioinformatics Vol. 26 no. 14 pages 1723–1730

2. Jungsun Park, Zuogang Peng, Jia Zeng, Navin Elango, Taesung Park,

Dave Wheeler, John H. Werren, and Soojin V. Yi (2011) Comparative Analyses

of DNA Methylation and Sequence Evolution Using Nasonia Genomes.

Molecular Biology and Evolution 28(12):3345-54

3.Jungsun Park, Ke Xu, Taesung Park and Soojin V. Yi (2012) What are the

determinants of gene expression levels and breadths in the human genome?

Human Molecular Genetics 21(1):46-56

4.Choi MR, In YH, Park J, Park T, Jung KH, Chai JC, Chung MK, Lee YS,

Chai YG (2012) Genome-scale DNA methylation pattern profiling of human bone

marrow mesenchymal stem cells in long-term culture Experimental & Molecular

Medicine 44(8):503-12

5.Seong-Keun Yoo, Byung Chan Lim, Jiyoung Byeun, Hee Hwang, Ki Joong

Kim, Yong Seung hwang, JoonHo Lee, Joong Shin Park, Yong-Sun Lee,

Junghyun Namkung, Jungsun Park, Seungbok Lee, Jong-yeon Shin, Jeong-

Sun Seo, Jong-Il Kim, and Jong Hee Chae (2015) Noninvasive Prenatal

Diagnosis of Duchenne Muscular DystrophyL Comprehensive Genetic Diagnosis

in Carrier, Proband, and Fetus. Clinical Chemistry 61(6):829-37

서울대학교 생물정보연구소

생물정보학 협동과정 공동주최