二零一零年第二次临时股东大会决议公.ppt

Bio 101: Genomics Computational Biology DNA1: Last weeks take-home lessons DNA2: Todays story and goals DNA 2 Applications of Dynamic Programming Alignments Scores Increasingly complex (accurate) searches Hardness of (multi-) sequence alignment Switch to protein searches when possible A Multiple Alignment of Immunoglobulins Scoring matrix based on large set of distantly related blocks: Blosum62 Scoring Functions and Alignments Scoring function: ?(match) = +1; ?(mismatch) = -1; ?(indel) = -2; ?(other) = 0. Alignment score: sum of columns. Optimal alignment: maximum score. Calculating Alignment Scores DNA2: Todays story and goals What is dynamic programming? Recursion of Optimal Global Alignments Recursion of Optimal Local Alignments Computing Row-by-Row Traceback Optimal Global Alignment Local and Global Alignments Time and Space Complexity of Computing Alignments Space Time Considerations Comparing two one-megabase genomes. Space: An entry: 4 bytes; Table: 4 * 10^6 * 10^6 = 4 Terabytes memory (one row at a time) Time: 1000 MHz CPU: 1M entries/second; 10^12 entries: 1M seconds = 10 days. Time Space Improvement for w-band Global Alignments Two sequences differ by at most w bps (wn). w-band algorithm: O(wn) time and space. Example: w=3. Summary Dynamic programming Statistical interpretation of alignments Computing optimal global alignment Computing optimal local alignment Time and space complexity Improvement of time and space Scoring functions DNA2: Todays story and goals A Multiple Alignment of Immunoglobulins A multiple alignment = Dynamic programming on a hyperlattice Multiple Alignment vs Pairwise Alignment Computing a Node on Hyperlattice Challenges of Optimal Multiple Alignments Space complexity (hyperlattice size): O(nk) for k sequences each n long. Computing a hyperlattice node: O(2k). Time complexity: O(2knk). Find the optimal solution is exponential in k (non-polynomial, NP-hard). Methods and Heuristics for Optimal Multiple Alignments Op