-疾病治疗老年视黄斑退化.pdf

An Efficient Index Structure for siRNA Off-target Search Anthony J.T. Lee, Chao-Wen Lin, Jia-Xin Chen and Yu-Keng Shih NTU, IM Motivation • siRNA – Small interfering RNA • a class of 20-25 nucleotide-long double-stranded RNA molecules – RNA interference • Gene knockdown – 疾病治療 ：老年視黃斑退化、肌萎縮側索硬化 症、類風濕性關節炎 、肥胖症等；抗病毒治療 方面 ：帕金森病等；腫瘤 Motivation • Off-target Effect – One of the most important problems in silencing an RNA pathway. – siRNA knockdowns the non-targeted genes, which have homology to the targeted gene • Off-target Search – Identify sequences for the gene of interest, compare the candidate sequences with an applicable genome database and show no evident homology to other genes. Problem Defined • Gene Expression – ‘A’, ’C’, ’G’, and ‘T’ • String Matching – Length : 19 • Hamming Distance String 1 A T G C A T G String 2 A G G C T T G Distance = 2 • Mismatch Tolerance Trivial Method • Compute distance between query siRNA sequence and each sequence in database – It’s very inefficient • Compute every candidate and find them in database – Total C(19, 3)*3^4 candidates – How to find them in database efficiently? • How to improved? Our Method: CPI • Common Prefix Indexing • Concept – Some sequences have common prefix, so we only need to compute distance of prefix first – If the distance of prefix exceed mismatch tolerance, we ignore sequences with this prefix. – If the distance is less than mismatch tolerance, we find all candidates and check them. • How to implement this concept efficiently – Build index tab