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Physical Mapping Problem. D7526010@csie.ntu.edu.tw. Problem Definition. Physical mapping 的定義. H J. DNA. A. B. Q. C. P. D. O. N. E. M. F. G. L. H. K. J. Fragment of DNA. Why We Need Physical Mapping. 可以利用這個地圖將 DNA 做完全排序 可以知道基因到底如何對人類產生作用 利用人造蛋白質 ... 等等來改進遺傳體質.

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## Physical Mapping Problem

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**Physical Mapping Problem**D7526010@csie.ntu.edu.tw**Problem Definition**• Physical mapping的定義**H J**DNA A B Q C P D O N E M F G L H K J Fragment of DNA**Why We Need Physical Mapping**• 可以利用這個地圖將DNA做完全排序 • 可以知道基因到底如何對人類產生作用 • 利用人造蛋白質...等等來改進遺傳體質**人類染色體(約 bp)**Physical map (約 bp) AGACTAGTCGTAACGATCGCTAATTTAAGGCTACT..... DNA Sequencing (約 bp)**Why We Need Physical Mapping**• 可以利用這個地圖將DNA做完全排序 • 可以知道基因到底如何對人類產生作用 • 利用人造蛋白質...等等來改進遺傳體質 • 可以得知基因(或標記)的大約位置 • 對於一些遺傳疾病可以得到較多的資訊 • 可以幫助偵測是否具有遺傳疾病**DNA**A B Q C P D O N E M F G L H K J Fragment of DNA H J α**target DNA**加入酵素**Partial Digest Problem**• by single enzyme A • restriction sites: a1< a2< a3<.....< ap • multiset of fragment lengths {aj-ai,i<j}**Double Digest Problem (DDP)**• Clones first completely digested by enzyme A,then by B, finally A and B together • restriction sites: • by A: a1< a2< a3<.....< ap • by B: b1< b2< b3 <.....< bq • by A+B : c1< c2< c3 <.....< cp+q • Reconstruct the restriction sites from these multisets**Example : DDP**Enzyme A+B 1 2 3 3 5 6 7 Enzyme A 3 6 8 10 Enzyme B 4 5 7 11**target DNA**........**target DNA**................. ........ ATGCGCTAACTGGACTTCAAGCCTAAACTGCATCAGACTT TACGCGATTGACCTGAAGT Complementary probe The Spirit of Hybridization**target DNA**A B 1 2 3 4 5 C D E F G H I J**J D F I E G A C H B**1 2 3 4 5**1**A、B、C C、D、E 2 3 E、F F、G 4 G、H、I 5 6 I、J、K False Negative 1 A、C C、D、E 2 3 E、F A、F、G 4 G、H、I 5 6 E、F、I、J、K**1**A、B、C C、D、E 2 3 E、F F、G 4 G、H、I 5 6 I、J、K False Positive 1 A、C C、D、E 2 3 E、F A、F、G 4 G、H、I 5 6 E、F、I、J、K**Chimeric Clones**1 A、C 1 A、B、C C、D、E 2 C、D、E 2 3 E、F 3 E、F A、F、G 4 F、G 4 G、H、I 5 G、H、I 5 6 E、F、I、J、K 6 I、J、K**5**A、B、C C、D、E 6 3 E、F F、G 4 I、J、K 1 2 G、H、I Clones 1 2 3 4 5 6 A B Probes C D E F G H I J K**Clones**1 2 3 4 5 6 A 5 A、B、C B Probes C、D、E 6 C 3 E、F、K D I、J、K、F、G E 4 F I、J、K 1 G H 2 G、H、I I J K**How To Use Traveling Salesman Problem to Solve Physical**Mapping Problem**How to Convert to TSP?**• Hamming distance**How to Convert to TSP?**• Hamming distance • Cycle weight = number of gaps transitions +2n**How to Convert to TSP?**• Hamming distance • Cycle weight = number of gaps transitions +2n • So, minimize the cycle weight is to the gap number**Our approach**• We also convert it to optimization problem • Using more complicated model • Using Genetic Algorithm to solve it. F(A) = X*C(A)+Y*P(A)+Z*N(A)+T*M(A)+ P*L(A).**The results of our approach tested on simulated data.**• (a) (b) • The false negative rate is set as 0.1. The false positive rate is 0.05. • The false negative rate is set as 0.1. The false positive rate is 0.01.**Experimental Results of our GA tested on Real data from**chromosome 1 (a) It shows the results of our GA run with the data which is a contig with about 95 clones and about 120 probes (b) It shows the results of our GA run with the data which is a contig with about 172 clones and about 136 probes

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