1. Synthetic Sequence Design for Signal Location Yaw-Ling Lin ( 林 耀 鈴 ) Dept Computer Sci and Info Engineering College of Computing and Informatics Providence University, Taiwan E-mail: yllin@pu.edu.tw http://www.cs.pu.edu.tw/~yawlin 2015/12/21Synthetic Design for Signal Location1

2. Outline Motivation Introduction Terminology Definition Signal location search Group testing designs Adjacent levels of the Hasse diagram Suggested Designations Conclusion 2015/12/21Synthetic Design for Signal Location2

3. Synthetic Biology 2015/12/21Synthetic Design for Signal Location3

4. Synthetic Biology 2015/12/21Synthetic Design for Signal Location4

5. What have we done with synthesis 2015/12/21Synthetic Design for Signal Location5

6. Introduction Large-scale synthesis opens new doors for rapid signal detection: –Replace a wild type gene coding sequence (W) with a different but synonymous encoding (D). –If the phenotype changes (e.g., the organism dies), it implies that there must be a critical signal at some location within that region. 2015/12/21Synthetic Design for Signal Location6

7. Contribution A Group-Testing Approach for Biological Signal Location. Group Testing for Expensive Pools. Improved Designs for Consecutive Positive Group Testing. Middle-Levels Conjecture Equivalence. Web link: http://www.algorithm.cs.sunysb.edu/signalSearch. http://www.algorithm.cs.sunysb.edu/signalSearch 2015/12/21Synthetic Design for Signal Location7

8. Biological Signal Location 2015/12/21Synthetic Design for Signal Location8

9. Design criteria for sequence signal search Experiences with polio and adenovirus. To construct t tests (design sequences) capable of pinpointing the location of a signal of length at most m (~20 to 60) bases as tightly as possible in a region of length g (~2k nt). We aim to partition the region into n segments and construct t tests to determine which segment contains the critical signal. 2015/12/21Synthetic Design for Signal Location9

10. A Simple Design and Challenges In the previous design, n = 16 and t = 4. Multiple Signals? Region Boundaries? Experimental Robustness? 2015/12/21Synthetic Design for Signal Location10

11. 2-consecutive positive matrix 2015/12/21Synthetic Design for Signal Location11 A cyclic 2-consecutive positive detectable matrix such that its column is a k-set (out of t elements) such that each two adjacent k-sets has distinct unions which are (k+1)-sets.

12. Middle Level Conjecture 2015/12/21Synthetic Design for Signal Location12

13. Middle Level Coverage 2015/12/21Synthetic Design for Signal Location13

14. Adjacent Level Lemma 2015/12/21Synthetic Design for Signal Location14

15. Cycles crossing adjacent levels 2015/12/21Synthetic Design for Signal Location15 Shimada and Amano (2011), running time about 81 days:

16. Consecutive Positives Detectable Matrix 2015/12/21Synthetic Design for Signal Location16

17. Main result: Non-adpative Group Testing 2015/12/21Synthetic Design for Signal Location17

18. 2015/12/21Synthetic Design for Signal Location18 Designing Consecutive Positives Detectable Matrix

19. Experiment Results 2015/12/21Synthetic Design for Signal Location19

20. Consecutive Positives Detectable Matrix 2015/12/21Synthetic Design for Signal Location20

21. Design Efficiency 2015/12/21Synthetic Design for Signal Location21 Our design: Colbourn’s design (1999): In particular, for r=3, d=3, Colbourn’s design create an 10 x 16 matrix; while our design, M 3 (7,3) gives a 10 x 105 matrix.

22. Conclusion We give a new class of consecutive positive group testing designs, which offer a better tradeoff of cost, resolution, and robustness than previous designs for signal search. Let n be the number of distinct regions, and d the number of consecutive positives regions. The design identifies the positive regions using t tests, where Given the target sequence, we propose one/two-round designs to maximize the number of inspected items n (therefore minimized boundary resolution). Future works: faults-detecting decoding algorithms. 2015/12/21Synthetic Design for Signal Location22

23. Conclusion (Theory) Equivalence of middle level conjecture to the adjacent level conjecture. Improvement of the consecutive positive matrix design. Future and continuous works: o More than one consecutive positives. o Efficient algorithms for false reads. o TagSNP selection in the haplotype block. o Further experiments on related biomedical haplotype data. 2015/12/21Synthetic Design for Signal Location23

24. Thank You! Any Question? 2015/12/21Synthetic Design for Signal Location24

25. 2015/12/21Synthetic Design for Signal Location25

26. Thank you. Q&A 2015/12/21Synthetic Design for Signal Location26

27. What Weekday is Today? Magic Number: -4/4, 6/6, 8/8, 10/10, 12/12 -7/11, 9/5 [also 11/7, 5/9] -3/0? [implying 2/28, 2/0 = 1/31] Extension: -365 = 52 * 7 + 1 -Leap Year? 2012:3; 2013:4; 2014:5; 2015:6; 2016:1 20yy: [5yy/4]+2 mod 7 2015/12/21Synthetic Design for Signal Location27