초록

1. 공개된 또는 공동연구팀의 공동 작업을 통해 새로이 생성한 화학유전체 프로파일을 체계적으로 DB화 2. DB화 된 프로파일을 이용하여 효모 생체 네트워크에 기반을 둔 분석 모델을 개발 3. 분석모델을 이용하여 보다 정교한 효모 생체 네트워크 모델을 개발 4. 분석모델을 바탕으로 기존에 기능이 잘 알려지지 않은 천연물의 세포내 기능을 예측하고 기존 약물이 세포 성장에 미치는 특이적인 저해 기전을 규명

Abstract ▼

The chemical-genetic profile can be defined as quantitative values of deletion strains' growth defects under exposure to chemicals. In yeast, the compendium of chemical-genetic profiles of genomewide deletion strains under many different chemicals has been used for identifying direct target proteins

The chemical-genetic profile can be defined as quantitative values of deletion strains' growth defects under exposure to chemicals. In yeast, the compendium of chemical-genetic profiles of genomewide deletion strains under many different chemicals has been used for identifying direct target proteins and a common mode-of-action of those chemicals. In the previous study, valuable biological information such as protein?protein and genetic interactions has not been fully utilized. In our study, we integrated this compendium and biological interactions into the comprehensive collection of ~490 protein complexes of yeast for model-based prediction of a drug's target proteins and similar drugs. We assumed that those protein complexes (PCs) were functional units for yeast cell growth and regarded them as hidden factors and developed the PC-based Bayesian factor model That relates the chemical-genetic profile at the level of organism phenotypes to the hidden activities of PCs at the molecular level. The inferred PC activities provided the predictive power of a common mode-of-action of drugs as well as grouping of PCs with similar functions. In addition, our PC-based model allowed us to develop a new effective method to predict a drug's target pathway, by which we were able to highlight the target-protein, TOR1, of rapamycin. Our study is the first approach to model phenotypes of systematicdeletion strains in terms of protein complexes. We believe that our PC-based approach can provide an appropriate framework for combining and modeling several types of chemical-genetic profiles including interspecies. Such efforts will contribute to predicting more precisely relevant pathways including target proteins that interact directly with bioactive compounds.

목차 Contents

• 제출문 ...1
• 보고서 요약서 ...2
• 요약문 ...3
• SUMMARY ...5
• CONTENTS ...6
• 목차 ...7
• 제1장 연구개발과제의 개요 ...8
• 제1절 연구개발의 목적...8
• 제2절 연구개발의 필요성...8
• 제2장 국내외 기술개발 현황 ...15
• 제1절 국내?외 관련분야에 대한 기술개발현황...15
• 제2절 현기술상태의 취약성...17
• 제3장 연구개발수행 내용 및 결과 ...19
• 제4장 목표달성도 및 관련분야에의 기여도 ...40
• 제5장 연구개발결과의 활용계획 ...44
• 제6장 연구개발과정에서 수집한 해외과학기술정보 ...45
• 제7장 참고문헌 ...46