Feasibility study of an evaluation of the impact of rare variants on gene expression

Research Project

Project/Area Number	16K12519
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Life / Health / Medical informatics
Research Institution	Tohoku University
Principal Investigator	Kinoshita Kengo 東北大学, 情報科学研究科, 教授 (60332293)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	ゲノム / レアバリアント / 発現量 / 発現量変化 / ゲノム変異 / バイオインフォマティクス / 生命情報 / 変異 / 遺伝子発現量
Outline of Final Research Achievements	The effect of mutations on expression levels is still largely unknown and very challenging. To begin with, the large-scale analysis of expression level data was carried out focusing on A 562 and K 549 cells as a pretreatment for the collection of basic data and the full-scale analysis. We also collected and analyzed ChIP-seq data in the public database for the analysis of transcription factor binding sites. In conducting these analyses, we were able to develop our own analysis methods, such as accurate library length estimation for Matataki and ChIP-seq. In the future, while utilizing the elemental methods developed in this research project, they will be deployed to a wider variety of cells and will not lead to the development of methods for the impact analysis of mutations in non-coding regions.
Academic Significance and Societal Importance of the Research Achievements	変異が発現量に及ぼす影響に関して、その重要性はこれまでも繰り返し指摘されてきた問題である。これに対して、個別研究の蓄積はある一方で、どのような変異がどのように発現量に影響を与えるかの一般的な関係性は未だ明らかではない。一般的には、転写因子の結合部位に入る変異が重篤な影響を与える事が予想されるが、その一方で、ChIP-seqやHi-Cなどの研究データが明らかにしたように、ヌクレオソームの状態や遺伝子配列の空間的な近さなど大きなゲノム構造の影響など、未だ明らかになっていない部分も多い。本研究では、変異の発現量に与える影響を俯瞰的に見る事で、レアバリアントの評価に大きな影響を与えることが期待される。