1、2010 Bioinformatics IF:4.877,Inferring the human microRNA functional similarity and functional network based on microRNA-associated diseases,整體思路,miRNA,disease,通過兩個疾病集合的相似性衡量兩個miRNA的相似性,基本假設(shè)：相似的miRNA通常和相似的疾病相關(guān)聯(lián),兩個疾病集合的相似性,假設(shè)已知兩個疾病的相似性,則一個 疾病和一個疾病集合的相似性定義為,兩個疾病集合的相似性定義為,也就是兩個miRNA的相似性,兩個疾病集合的相似性,Cont

2、ents,Abstract,Motivation 對于gene功能相似性和功能網(wǎng)絡(luò)的研究是很普遍的，也是有意義的，由于miRNA功能注釋的有限性，對miRNA 功能相似性的研究很少 Results,本文的貢獻,Introduction,研究領(lǐng)域,前人的工作,問題所在,Introduction,Gene功能相似性： 序列 表達 功能(注釋到GO),本文的 工作,序列和表達相似性并不總是和功能相似性相關(guān)的 靶基因有較高的假陽性和假陰性率,Methods,MeSH disease DAG structure Human miRNA-disease association data Method fo

3、r measuring miRNA functional similarity Semantic value of a disease Semantic similarity of two diseases miRNA MISIM functional similarity Construction of miRNA functional network,miRNA功能相似性衡量方法,miRNA-Disease,Methods,MeSH Category C,miRNA:271個 Disease:137個,Disease DAG,Sementic value of a disease,疾病 t

4、 在疾病A的 DAGA中對疾病 A 的語義值的貢獻稱為 t 的 D 值，記為 DA(t),Semantic value of a disease,語義貢獻因子 本文取0.5,Semantic similarity of two diseases,一個疾病和一個疾病集合的相似性,兩個miRNA的功能相似性,Results,MISIM functional similarity of miRNAs miRNA MISIM functional similarity is correlated with expression similarity miRNAs in the same family

5、or cluster show high MISIM functional similarity Novel highly functionally similar miRNAs MISIM functional similarity of two miRNAs is correlated with the fraction of their common targets A miRNA functional network Comparisons with other semantic similarity methods,positive correlation,Results,expre

6、ssion similarity,same family or cluster,novel highly functional similar miRNAs,相似性分數(shù)比隨機的高,positive correlation,Results,expression similarity,same family or cluster,novel highly functional similar miRNAs,相似性分數(shù)比隨機的高,positive correlation,miRNA和其宿主基因傾向于共表達，看宿主基因的功能,Results,expression similarity,same fam

7、ily or cluster,novel highly functional similar miRNAs,邏輯關(guān)系 假設(shè)：若兩個內(nèi)含子miRNA的宿主基因功能相關(guān)， 則這兩個miRNA功能相關(guān). 分析：得分高的兩個miRNA其宿主基因的功能若重 疊很多，則它們功能相關(guān). 高分的miRNA傾向于功能相關(guān),positive correlation,Results,fraction of their common targets,miRNA functional network,other semantic similarity methods,文中選取閾值 0.7,positive correlation,Results,fraction of their common targets,miRNA functional network,other semantic similarity methods,it seems that the cutoff 0.7 or 0.8 is suitable for the construction of miRNA functional networks.,文中選取閾值 0.7,positive correlation,不如本文的方法好,Results,fraction of their common targets,m