CS176: Genome Assembly
- 1. Genome Assembly Frank Austin Nothaft CS176, 10/16/2014
- 2. Processing Reads • As we’ve covered before, if we already have a reference assembly, we can process reads by aligning to the reference genome
- 3. The Sequencing Abstraction It was the best of times, it was the worst of times… worst of times was the worst the worst of • Sequencing performs a poisson distributed sampling of substrings from a larger string • Reads are exact substrings (i.e., error free) Metaphor borrowed from Michael Schatz It was the the best of times, it was best of times
- 4. The Alignment Abstraction It was the best of times, it was the worst of times… It was the the best of times, it was worst of times the worst of best of times was the worst was the worst It was the worst of times the best of the worst of times, it was best of times
- 5. But! • What do we do if we don’t have a reference genome to map against? • Can we use information in the reads to assemble the reads together into a string?
- 6. Sequence Assembly was the worst best of times It was the worst of times the best of the worst of times, it was It was the the best of best of times times, it was was the worst the worst of worst of times It was the best of times, it was the worst of times…
- 7. The Assembly Problem • Given a set of reads, we want to assemble the “best” contigs possible • Contig = contiguous sequence • Two general formulations for assembly: • Overlap-layout-consensus (OLC) • de Brujin graph (DBG)
- 8. Assembly was the Human Genome Project! (in a nutshell)
- 9. Assembly is Graph Traversal • In OLC, we create an overlap graph, and find a Hamiltonian path • In DBG, we create a de Brujin graph, and find an Eulerian path
- 10. Overlap Graphs • Given a set of reads, represents how these reads overlap Nodes are reads, edges are overlaps.
- 11. Example Overlap Graph It was the the best of times, it was the worst of worst of times best of times was the worst the best of It was the times, it was worst of times the worst of best of times was the worst
- 12. Hamiltonian Path • A Hamiltonian Path is a path which visits each node in the graph exactly once
- 13. Computing Overlaps • To compute overlaps between two reads, we compute the pairwise alignment of these two reads • This can be done using dynamic programming (Smith-Waterman) or a profile HMM • We can accelerate this with indexing-based methods, similar to those in SNAP
- 14. Two Problems 1. Overlapping is expensive: • Must compute O(n2) overlaps, n = # reads • Computing an overlap is O(l2), l = read length 2. Hamiltonian Path is NP-hard: • Approximate solvers exist, but don’t scale up to genomics datasets
- 15. de Brujin Graphs • In a de Brujin graph, nodes are k-mers, and edges represent observed transitions between k-mers • k-mers are k-length substrings from reads ACACTGCACT ACCAAC ACT CTG T GGCCA C AACCT
- 16. de Brujin Graphs • In a de Brujin graph, we may have multiple paths between two nodes ACACTGCACT ACCAAC ACT CTG T GGCCA C AACCT ACA CAC ACT GCA TGC CTG
- 17. Eulerian Path • In an Eulerian path, we use every edge exactly once • Preconditions for finding an Eulerian path assembly on a DBG: 1. One node must have one more edge leaving than entering 2. One node must have one more edge entering than leaving 3. All other nodes must have equal numbers of edges entering and leaving
- 18. Finding an Eulerian Path • Connect the two nodes with unbalanced edges • This provides us an Eulerian cycle • From an arbitrary node n, walk the graph until we return from n, and save the path we’ve walked • Until all edges have been used: • Pick a point n’ from our path, where n’ has unused edges • Walk from n’ until we return to n’, and track visited edges
- 19. Problems with Eulerian Path • For a given graph, we may have multiple valid paths! CAA AAT 8 9 1 2 ACA CAC ACT GCA TGC CTG 10 ATG 7 3 5 4 6 11 ACACTGCACAATGC CAA AAT 1 2 8 9 ACA CAC ACT GCA TGC CTG 3 ATG 7 10 5 11 6 4 ACAATGCACACTGC
- 20. How Many Paths? Kingsford et al, BMC Bioinformatics 2010
- 21. How Do We Assemble Multiple Reads? • In practice, de Brujin graphs are additive • This allows us to merge graphs from multiple reads • When do we keep/remove edges?
- 22. ACACTGC ACCAAC ACT CTG TGC CAC ACT GCA TGC CTG CTGCACT CTG T GGCCA C AACCT ACA CAC ACT TGC CTG ACA CAC ACT GCA TGC CTG
- 23. Errors! • One of the key assumptions that we make in the sequencing process is that reads are correct • But, in reality, reads have a 2% error rate • How does this impact us?
- 24. What Are The Errors Like? ACATATAGAA AGATATAGAN • Currently, the most common sequencing technology is called Illumina • Errors tend to be a misread of a single base • Errors tend to be clustered at the ends of reads
- 25. Errors In Action ACCCAAATCTAATCAAGGC CCCAAATCTAATCAAGGCT ACTCTACCTCCCAAGCTCT CTCTACCTCCCAAGCTCTA TCTACCTCCCAAGCTCTAG CTACCTCCCAAGCTCTAGG CCAAATCTAATCAAGGCTC CAAATCTAATCAAGGCTCC AAATCTAATCAAGGCTCCC AATCTAATCAAGGCTCCCA CTAACTCCCAAGCTCTAGG AAAGGAAGATCATGAAATA AAGGAAGATCATGAAATAC AGGAAGATCATGAAATACC GGAAGATCATGAAATACCA GAAGATCATGAAATACCAC AGATCATGAAATACCACCA CATGAAATACCACCATGGG ATGAAATACCACCATGGGG TGAAATACCACCATGGGGA ATGGGGATTCAATCAGCAA TGGGGATTCAATCAGCAAA GGGGATTCAATCAGCAAAT GGGGATTCAATCAGCAAAG GGGATTCAATCAGCAAATT GGGATTCAATCAGCAAAGT AGATTCAATCAGCAAATTC AGCAAATTCTGAAATGCAT AGCAAATTCTGAAATGCAA GTGAAATGCAACATTGCCA TGAAATGCAACATTGCCAT GAAATGCAACATTGCCATT CATTGCCATTTACCCTGCT ATTGCCATTTACCCTGCTT TTGCCATTTACCCTGCTTG TCTGAGGAAGAATTTGAGA TGAGGAAGAATTTGAGATG GAGGAAGAATTTGAGATGA AGGAAGAATTTGAGATGAG GGAAGAATTTGAGATGAGG GACTAAGGAAGATCATGAA ACTAAGGAAGATCATGAAA CTAAGGAAGATCATGAAAT ACTCCCAAGCTCTAGGATA CTCCCAAGCTCTAGGATAT TCCCAAGCTCTAGGATATA AGAATTTGAGATGAGGGGA AATTTGAGATGAGGGGACG ATTTGAGATGAGGGGACGG TTTGAGATGAGGGGACGGA GAGGGGACGGATTTGCTGC AGGGGACGGATTTGCTGCC GGGGACGGATTTGCTGCCT GAGATTCAATCAGCAAATT CAGCCAATTCTGAAATGCA AGCCAATTCTGAAATGCAA GCCAATTCTGAAATGCAAC CCAATTCTGAAATGCAACA CAATTCTGAAATGCAACAT AATTCTGAAATGCAACATT CATTATCCTTCACCCCGCT ATTATCCTTCACCCCGCTT TTATCCTTCACCCCGCTTG TATCCTTCACCCCGCTTGG ATCCTTCACCCCGCTTGGC TCCTTCACCCCGCTTGGCC TGCCATTTACCCTGCTTGG GCCATTTACCCTGCTTGGC ATTTACCCTGCTTGGCCTA TTTACCCTGCTTGGCCTAA CCCCTGCTTGGCCTAAAAG CCCTGCTTGGCCTAAAAGT CCTAAAAGTTCAAAATAAC CTAAAAGTTCAAAATAACA TACCAGAGCCTGTTATATT ACCAGAGCCTGTTATATTT CCAGAGCCTGTTATATTTT CATGAAATACCACCATGGT ATGAAATACCACCATGGTG TGAAATACCACCATGGTGA NGGATTCAATCAGCAAATT ATTCAATCAGCAAATTCTG TTCAATCAGCAAATTCTGA TCAATCAGCAAATTCTGAA CAATCAGCAAATTCTGAAA AATCAGCAAATTCTGAAAT TTTGCTGCCTCTGAGGAGG TTGCTGCCTCTGAGGAGGG TGCTGCCTCTGAGGAGGGC GAGGAGGGCATTAGAATAG AGGAGGGCATTAGAATAGA GGAGGGCATTAGAATAGAA ACTCCAGGAAAAAGTCAGC CTCCAGGAAAAAGTCAGCT TCCAGGAAAAAGTCAGCTG GCAAAGTCTGAAATGCAAC CAAAGTCTGAAATGCAACA ACATTATCCTTCACCCTGC CATTATCCTTCACCCTGCT ATTATCCTTCACCCTGCTT TATCCTTCACCCTGCTTGG ATCCTTCACCCTGCTTGGC TCCTTCACCCTGCTTGGCC GGCCTAAAAGTACAAAAAA GCCTAAAAGTACAAAAAAA CCTAAAAGTACAAAAAAAC ATTCTGAAATGCATCATTA TTCTGAAATGCATCATTAT TCTGAAATGCATCATTATC CTGAAATGCATCATTATCC TGAAATGCATCATTATCCT CTTCCCCCTGCTTGGCCTA CCCCCTGCTTGGCCTAAAA CCTGCTTGGTCTAAAAGTA CTGCTTGGTCTAAAAGTAC TGCTTGGTCTAAAAGTACA AAAAGTACAAAATAACACG AAAGTACAAAATAACACGA AAGTACAAAATAACACGAA TACAAAATAACACGAAGAA ACAAAATAACACGAAGAAA CAAAATAACACGAAGAAAA ACACGAAGAAAAATTAGTT CACGAAGAAAAATTAGTTT ACGAAGAAAAATTAGTTTC AGAAAAATTAGTTTCCAGA GAAAAATTAGTTTCCAGAG AAAAATTAGTTTCCAGAGC CCCAAGCTCTAGGACATAC CCAAGCTCTAGGACATACC ACATACCAAGGACAAAGGA CATACCAAGGACAAAGGAA ATACCACCATGGTGATTCA TACCACCATGGTGATTCAA ACCACCATGGTGATTCAAT CCACCATGGTGATTCAATC GGTCTAAAAGTACAAAATA GTCTAAAAGTACAAAATAA TCTAAAAGTACAAAATAAC CCATGGGGATTCGATCAGC CATGGGGATTCGATCAGCA ATGGGGATTCGATCAGCAA ACAAAAAAACACGAAGAAC CAAAAAAACACGAAGAACC ACGAAGAACCATTAGTTAC CCAGAGCCAGTTATATTTT CAGAGCCAGTTATATTTTG AGAGCCAGTTATATTTTGA TACCAAGGACAAAGGAAGA ACCAAGGACAAAGGAAGAT CCAAGGACAAAGGAAGATC CCTGCTTGACTTAAAAGTA CTGCTTGACTTAAAAGTAC TGCTTGACTTAAAAGTACA GCTCTAGGACATACCAAGG CTCTAGGACATACCAAGGA TCTAGGACATACCAAGGAC AATCAGCAAAGTCTGAAAT ATCAGCAAAGTCTGAAATG TCAGCAAAGTCTGAAATGC GGAAGATCATGAAATCCCA GAAGATCATGAAATCCCAC AAGATCATGAAATCCCACC NNNNNNNNNNNNTTTCTGA NNNNNNNNNNNTTTCTGAA NNNNNNNNNNTTTCTGAAT CCAGAGCCAGTTATACTTT CAGAGCCAGTTATACTTTG AGAGCCAGTTATACTTTGA ATGAAATCCCACCATGGGG TGAAATCCCACCATGGGGA GAAATCCCACCATGGGGAT AATCAGCCAATTCTGAAAT ATCAGCCAATTCTGAAATG TCAGCCAATTCTGAAATGC GATTCAATCAGCAAATTCT CCAGGAAAAAGTCAGCTGT CAGGAAAAAGTCAGCTGTG AGGAAAAAGTCAGCTGTGT AATAACACGAAGAAAAATT ATAACACGAAGAAAAATTA TAACACGAAGAAAAATTAG GCCAGTTATATTGTTAAAA CCAGTTATATTGTTAAAAA CAGTTATATTGTTAAAAAT AGTTATATTGTTAAAAATC TAAAAATCACCCAAAAACC AAAAATCACCCAAAAACCA AATCAACGATAGAATATAC ATCAACGATAGAATATACA TCAACGATAGAATATACAG GCCAGTTATATTTTGAAAA CCAGTTATATTTTGAAAAA GCCTAAAAGGACAAAACAA CCTAAAAGGACAAAACAAC CTAAAAGGACAAAACAACA AAAATAACACGAGGAAAAA AAATAACACGAGGAAAAAT AATAACACGAGGAAAAATT GCTTGACTTAAAAGTACAA AACTCCCAAGCTCTAGGAC ACTCCCAAGCTCTAGGACA CTCCCAAGCTCTAGGACAT GAAGAACCATTAGTTACCA AAGAACCATTAGTTACCAG AGAACCATTAGTTACCAGA TCCCAAGCTCTAGGACATA ATCCTTCCCCCTGCTTGGC TCCTTCCCCCTGCTTGGCC CCTTCCCCCTGCTTGGCCT ATCACCCAAAAACCAAGAA TCACCCAAAAACCAAGAAT CACCCAAAAACCAAGAATC AAGGACAAAGGAAGATCAT AGGACAAAGGAAGATCATG GGACAAAGGAAGATCATGA AAAAACACGAAGAACCATT AAAACACGAAGAACCATTA AAACACGAAGAACCATTAG GAGCCAGTTATATTTTGAA AGCCAGTTATATTTTGAAA TTAGTTTCCACAGCCTGTT TAGTTTCCACAGCCTGTTA AGTTTCCACAGCCTGTTAT CCATCGGAATCCACTCAGC CATCGGAATCCACTCAGCA ATCGGAATCCACTCAGCAA ATACCAAGGACAAAGGAAG GGGACGGATTTGCTGCCTC GGACGGATTTGCTGCCTCT CAAAGCTAATCAAGGCTCC AAAGCTAATCAAGGCTCCC AAGCTAATCAAGGCTCCCA ATTAGTTTCCAGAGCCAGT TTAGTTTCCAGAGCCAGTT TAGTTTCCAGAGCCAGTTA TACCTCCCAAGCTCTAGGA ACCTCCCAAGCTCTAGGAT CCTCCCAAGCTCTAGGATA TGCAACATTGCCATTTACC GCAACATTGCCATTTACCC CAACATTGCCATTTACCCT AAATCCCACCATGGGGATT AATCCCACCATGGGGATTC ATCCCACCATGGGGATTCA CAGCAAATTCTGAAATGCN AGCAAATTCTGAAATGCNN GCAAATTCTGAAATGCNNN AAATGCNNNNNNNNNNNNN AATGCNNNNNNNNNNNNNN ATGCNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNANAT NNNNNNNNNNNNNNANATT NNNNNNNNNNNNNANATTN ATCAAGGCTCCCACTCTAC TCAAGGCTCCCACTCTACC CAAGGCTCCCACTCTACCT TTATCCTTCACCCTGCTTG TATCCTTCACCCTGCTTGA CCAAGCTCTAGGATATACC CAAGCTCTAGGATATACCA AAGCTCTAGGATATACCAA AGAATCAACGATAGAATAT GAATCAACGATAGAATATA CTCAGCAAATTCTGAAATG TCAGCAAATTCTGAAATGC CAGCAAATTCTGAAATGCA ATATTGTTAAAAATCACCC TATTGTTAAAAATCACCCA ATTGTTAAAAATCACCCAA GATCATGAAATCCCACCAT ATCATGAAATCCCACCATG TCATGAAATCCCACCATGG TTCCACAGCCTGTTATATT TCCACAGCCTGTTATATTT CCACAGCCTGTTATATTTT GAAATACCACCATGGTGAT AAATACCACCATGGTGATT AATACCACCATGGTGATTC CCATGNGGATTCAATCAGC CATGNGGATTCAATCAGCA ATGNGGATTCAATCAGCAA GCCTGTTATATTTTGAAAA CCTGTTATATTTTGAAAAC CCTGTTATATTTTGAAAAA TAGACCAAGGACAAAGGAA AGACCAAGGACAAAGGAAG GACCAAGGACAAAGGAAGA TGCCTCTGAGGAGGGCATT GCCTCTGAGGAGGGCATTA CCTCTGAGGAGGGCATTAG ATCTAATCAAGGCTCCCAC TCTAATCAAGGCTCCCACT CTAATCAAGGCTCCCACTC TATACCAAGGACAAAGGAA TCACCCTGCTTGGCCTAAA CACCCTGCTTGGCCTAAAA ACCCTGCTTGGCCTAAAAG CAATCTGAGGAAGAATTTG AATCTGAGGAAGAATTTGA ATCTGAGGAAGAATTTGAG TCATTATCCTTCCCCCTGC CATTATCCTTCCCCCTGCT ATTATCCTTCCCCCTGCTT CTGCCTCTGAGGAGGGCAT CNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNT NNNNNNNNNNNNNNNNNNA AACGATAGAATATACAGTA ACGATAGAATATACAGTAC CGATAGAATATACAGTACA AATGCATCATTATCCTTCC ATGCATCATTATCCTTCCC TGCATCATTATCCTTCCCC AGTACAAAATAACACGAAG GTACAAAATAACACGAAGA TTACCAGAGCCTGTTATAT GTACATTCCTTCCCCGGAA TACATTCCTTCCCCGGAAG ACATTCCTTCCCCGGAAGC GTTTCCAGAGCCTGTTATA TTTCCAGAGCCTGTTATAT TTCCAGAGCCTGTTATATT AACTCCAGGAAAAAGTCAG TCGATCAGCAAATTCTGAA CGATCAGCAAATTCTGAAA GATCAGCAAATTCTGAAAT AGCTTCCACAGTTGCATCA GCTTCCACAGTTGCATCAG CTTCCACAGTTGCATCAGC GCATCATTATCCTTCCCCC CATCATTATCCTTCCCCCT ATCATTATCCTTCCCCCTG GATAGAATATACAGTACAT AAAATAACACGAAGAAAAA AAATAACACGAAGAAAAAT AGTTTCCAGAGCCTGTTAT AATTAGTTTCCAGAGCCAG TTATCCTTCCCCCTGCTTG TATCCTTCCCCCTGCTTGG GATAGACCAAGGACAAAGG ATAGACCAAGGACAAAGGA CAACGATAGAATATACAGT CCACCATCGGAATCCACTC CACCATCGGAATCCACTCA ACCATCGGAATCCACTCAG CTAGGACATACCAAGGACA TAGGACATACCAAGGACAA AGGACATACCAAGGACAAA AAAAAAACACGAAGAACCA AAAAAACACGAAGAACCAT CAAATTCTGAAATGCAACA AAATTCTGAAATGCAACAT GCTGCCTCTGAGGAGGGCA CCCCGCTTGGCCTAAAAGT CCCGCTTGGCCTAAAAGTA CCGCTTGGCCTAAAAGTAC GAATATACAGTACATTCCT AATATACAGTACATTCCTT ATATACAGTACATTCCTTC TGGGGATTCGATCAGCAAA GGGGATTCGATCAGCAAAT GGGATTCGATCAGCAAATT AACATTATCCTTCACCCTG CACTCTAACTCCCAAGCTC ACTCTAACTCCCAAGCTCT CTCTAACTCCCAAGCTCTA CTAAAAGTACAAAAAAACA CACCATGGTGATTCAATCA ACCATGGTGATTCAATCAG TAAAAGTACAAAAAAACAC TGGCCTAAAAGGACAAAAC GGCCTAAAAGGACAAAACA AATACCACCATGGGGATTC ATACCACCATGGGGATTCA TACCACCATGGGGATTCAA TAACTCCCAAGCTCTAGGA AACTCCCAAGCTCTAGGAT NATTAGTTTCCAGAGCCTG ATTAGTTTCCAGAGCCTGT TTAGTTTCCAGAGCCTGTT TCTGAAATGCAACATTATC CTGAAATGCAACATTATCC TGAAATGCAACATTATCCT TAGAATAACTCCAGGAAAA AGAATAACTCCAGGAAAAA GAATAACTCCAGGAAAAAG TTCACCCTGCTTGGCCTAA TAGTTACCAGAGCCTGTTA AGTTACCAGAGCCTGTTAT GTTACCAGAGCCTGTTATA TCCCACCATGGGGATTCAA CCCACCATGGGGATTCAAT CCACCATGGGGATTCAATC GAAGCTTCCACAGTTGCAT AAGCTTCCACAGTTGCATC ATTCTGAAATGCAACATTA TTCTGAAATGCAACATTAT AACATTGCCATTTACCCTG ACATTGCCATTTACCCTGC CGAAGAAAAATTAGTTTCC GAAGAAAAATTAGTTTCCA GATTCAATCAGCAAAGTCT ATTCAATCAGCAAAGTCTG TTCAATCAGCAAAGTCTGA GCCAGTTATACTTTGAAAA CCAGTTATACTTTGAAAAA ACCATGNGGATTCAATCAG CAAGAATCAACGATAGAAT AAGAATCAACGATAGAATA CACAGCCTGTTATATTTTG ACAGCCTGTTATATTTTGA CAGCCTGTTATATTTTGAA GGATTCGATCAGCAAATTC GATTCGATCAGCAAATTCT GAGGGCATTAGAATAGAAT AGGGCATTAGAATAGAATA GGGCATTAGAATAGAATAA CGAGGAAAAATTAGTTTCC GAGGAAAAATTAGTTTCCA AGGAAAAATTAGTTTCCAG CCATGGTGATTCAATCAGC AAATTCTGAAATGCNNNNN AATTCTGAAATGCNNNNNN ATTCTGAAATGCNNNNNNN ATTAGTTTCCACAGCCTGT TCGAGGAAAAATTAGTTTC AACACGAGGAAAAATTAGT ACACGAGGAAAAATTAGTT CACGAGGAAAAATTAGTTT TAGGATATACCAAGGACTA AGGATATACCAAGGACTAA GGATATACCAAGGACTAAG GTTTCCAGAGCCAGTTATA TTTCCAGAGCCAGTTATAT TTTCCAGAGCCAGTTATAC TTCCAGAGCCAGTTATATT TTCCAGAGCCAGTTATACT TGNGGATTCAATCAGCAAA GNGGATTCAATCAGCAAAT TCGGAATCCACTCAGCAAA CGGAATCCACTCAGCAAAT GGAATCCACTCAGCAAATT CTTCACCCCGCTTGGCCTA TTCACCCCGCTTGGCCTAA TCACCCCGCTTGGCCTAAA CTCGAGGAAAAATTAGTTT CCTTCACCCCGCTTGGCCT GTCTGAAATGCAACATTAT NNNNNNANATTNTNANAAA CGAAGAACCATTAGTTACC ATTCGATCAGCAAATTCTG TTCGATCAGCAAATTCTGA AGCCAATCTGAGGAAGAAT GCCAATCTGAGGAAGAATT CCAATCTGAGGAAGAATTT CACCCTGCTTGACTTAAAA ACCCTGCTTGACTTAAAAG CCCTGCTTGACTTAAAAGT AAAGTACAAAAAAACACGA AAGTACAAAAAAACACGAA AGTACAAAAAAACACGAAG CGGATTTGCTGCCTCTGAG GGATTTGCTGCCTCTGAGG GATTTGCTGCCTCTGAGGA CAATCAGCAAAGTCTGAAA ATGCAACATTATCCTTCAC TGCAACATTATCCTTCACC TGCAACATTATCCTTCACA GCAACATTATCCTTCACCC GCAACATTATCCTTCACAC TCCAGAGCCAGTTATATTT AAAATCACCCAAAAACCAA AAATCACCCAAAAACCAAG AATCACCCAAAAACCAAGA AAGTACAAAATAACACGAG AGTACAAAATAACACGAGG GTACAAAATAACACGAGGA AGTTTCCAGAGCCAGTTAT AGGCTCCCACTCTACCTCC GGCTCCCACTCTACCTCCC GCTCCCACTCTACCTCCCA CAAATTCTGAAATGCNNNN TGTTAAAAATCACCCAAAA GTTAAAAATCACCCAAAAA TTAAAAATCACCCAAAAAC TTCCTTCCCCGGAAGCTTC TCCTTCCCCGGAAGCTTCC CCTTCCCCGGAAGCTTCCA TATACCAAGGACTAAGGAA ATACCAAGGACTAAGGAAG TACCAAGGACTAAGGAAGA ATGAGGGGACGGATTTGCT TGAGGGGACGGATTTGCTG TGCNNNNNNNNNNNNNNNN GCNNNNNNNNNNNNNNNNN CCTTCACACTGCTTGGCCT CTTCACACTGCTTGGCCTA TTCACACTGCTTGGCCTAA CCACTCTAACTCCCAAGCT CCTGCTTGGCCTAAAAGTA CCGGAAGCTTCCACAGTTG CGGAAGCTTCCACAGTTGC GGAAGCTTCCACAGTTGCA CAAGGCTCCCACTCTAACT AAGGCTCCCACTCTAACTC AGGCTCCCACTCTAACTCC CCCAAGCTCTAGGATATAC AAATTCTGAAATGCATCAT AATTCTGAAATGCATCATT GTTTCCACAGCCTGTTATA TTTCCACAGCCTGTTATAT AAGATCATGAAATACCACC AACCATTAGTTACCAGAGC ACCATTAGTTACCAGAGCC CCATTAGTTACCAGAGCCT CAAGGACAAAGGAAGATCA CTTGACTTAAAAGTACAAA AGTTCAAAATAACACGAGG GTTCAAAATAACACGAGGA TTCAAAATAACACGAGGAA ATAACACGAGGAAAAATTA TTCCACAGTTGCATCAGCG TCCACAGTTGCATCAGCGT CCACAGTTGCATCAGCGTA CTCCCACTCTACCTCCCAA TCCCACTCTACCTCCCAAG CCCACTCTACCTCCCAAGC CAAGGACTAAGGAAGATCA AAGGACTAAGGAAGATCAT AGGACTAAGGAAGATCATG TGGTGATTCAATCAGCAAA GGTGATTCAATCAGCAAAT GTGATTCAATCAGCAAATT AGCCTGTTATATTTTGAAA AGATGAGGGGACGGATTTG GATGAGGGGACGGATTTGC GGAAAAATTAGTTTCCAGA TATACAGTACATTCCTTCC ATACAGTACATTCCTTCCC NNNNNNNNNNNNNNNNANA AATAACTCCAGGAAAAAGT ATAACTCCAGGAAAAAGTC TAACTCCAGGAAAAAGTCA AGCTAATCAAGGCTCCCAC GCTAATCAAGGCTCCCACT CTCTAGGATATACCAAGGA TCTAGGATATACCAAGGAC CTAGGATATACCAAGGACA CTAGGATATACCAAGGACT GGACTAAGGAAGATCATGA CAAAGGAAGATCATGAAAT AAAGGAAGATCATGAAATC AAGGAAGATCATGAAATCC GAGCCAGTTATACTTTGAA CAACATTATCCTTCACCCC CAACATTATCCTTCACCCT AACATTATCCTTCACCCCG CAGAGCCTGTTATATTTTG AGAGCCTGTTATATTTTGA TTGAGATGAGGGGACGGAT CAGTACATTCCTTCCCCGG AGTACATTCCTTCCCCGGA AGCTCTAGGATATACCAAG GCTCTAGGATATACCAAGG GCTTGGTCTAAAAGTACAA CTTGGTCTAAAAGTACAAA TTGGTCTAAAAGTACAAAA TTGTTAAAAATCACCCAAA TAGGATATACCAAGGACAA AGGATATACCAAGGACAAA GGATATACCAAGGACAAAG CCCAAAAACCAAGAATCAA CCAAAAACCAAGAATCAAC CAAAAACCAAGAATCAACG AATACCACCATCGGAATCC ATACCACCATCGGAATCCA TACCACCATCGGAATCCAC TTACCCTGCTTGGCCTAAA TACCCTGCTTGGCCTAAAA TTCACCCTGCTTGACTTAA TCACCCTGCTTGACTTAAA GACATACCAAGGACAAAGG ATCCTTCACCCTGCTTGAC TCCTTCACCCTGCTTGACT TCCAGAGCCAGTTATACTT ACCACCATCGGAATCCACT CACTCAGCAAATTCTGAAA ACTCAGCAAATTCTGAAAT TTAGAATAGAATAACTCCA TAGAATAGAATAACTCCAG AGAATAGAATAACTCCAGG TGGTCTAAAAGTACAAAAT GGAAAAAGTCAGCTGTGTT GAAAAAGTCAGCTGTGTTG TGCTTGGCCTAAAAGTACA GCTTGGCCTAAAAGTACAA CTTGGCCTAAAAGTACAAA GGATTCAATCAGCAAATTC NNNNNNNNNNNNNNNNNAN CCCCGGAAGCTTCCACAGT CCCGGAAGCTTCCACAGTT TATCCTTCACACTGCTTGG ATCCTTCACACTGCTTGGC TCCTTCACACTGCTTGGCC GAAATACCACCATGGGGAT AAATACCACCATGGGGATT AGATCATGAAATCCCACCA GAATAGAATAACTCCAGGA AATAGAATAACTCCAGGAA CAATCAGCCAATTCTGAAA GAAGAATTTGAGATGAGGG AAGAATTTGAGATGAGGGG TAACACGAGGAAAAATTAG AAATGCAACATTGCCATTT AATGCAACATTGCCATTTA ATGCAACATTGCCATTTAC TCACACTGCTTGGCCTAAA AAAAACCAAGAATCAACGA AAAACCAAGAATCAACGAT AAACCAAGAATCAACGATA TAGTTTCCAGAGCCTGTTA AGTCTGAAATGCAACATTA AACACGAAGAACCATTAGT ACACGAAGAACCATTAGTT CACGAAGAACCATTAGTTA ACAAAATAACACGAGGAAA CAAAATAACACGAGGAAAA NNNNNNNNNNNNNTTTCTG ATTAGAATAGAATAACTCC CCTTCACCCTGCTTGGCCT TCTAACTCCCAAGCTCTAG ATCCACTCAGCAAATTCTG TCCACTCAGCAAATTCTGA CCACTCAGCAAATTCTGAA CAACATTATCCTTCACACT AACATTATCCTTCACACTG NNNNNNNNNNNNNNNNNTT GAAATGCATCATTATCCTT AAATGCATCATTATCCTTC NNNNNNTTTCTGAATGTTT CTTCCCCGGAAGCTTCCAC TTCCCCGGAAGCTTCCACA TCCCCGGAAGCTTCCACAG GGATAGACCAAGGACAAAG CACCCCGCTTGGCCTAAAA ACCCCGCTTGGCCTAAAAG AAGAAAAATTAGTTTCCAG CATTCCTTCCCCGGAAGCT ATTCCTTCCCCGGAAGCTT CAGCAAAGTCTGAAATGCA AGCAAAGTCTGAAATGCAA CTTCACCCTGCTTGGCCTA CACTGCTTGGCCTAAAAGG ACTGCTTGGCCTAAAAGGA CTGCTTGGCCTAAAAGGAC ATCAGCAAATTCTGAAATG GAATTTGAGATGAGGGGAC GCTCCCACTCTAACTCCCA CTCCCACTCTAACTCCCAA TCCCACTCTAACTCCCAAG GAGCCTGTTATATTTTGAA AAAAAGTCAGCTGTGTTGA AAAAGTCAGCTGTGTTGAT GATATACCAAGGACTAAGG ATATACCAAGGACTAAGGA ATAGAATAACTCCAGGAAA NNNNNNNNNNNNNNTTTCT AATCAAGGCTCCCACTCTA ATCAAGGCTCCCACTCTAA TCAAGGCTCCCACTCTAAC CAAATACCACCATCGGAAT AAATACCACCATCGGAATC GCCTAAAAGTACAAAATAA CCTAAAAGTACAAAATAAC CTAAAAGTACAAAATAACA TTGGCCTAAAAGTACAAAA TGGCCTAAAAGTACAAAAT TGGCCTAAAAGTACAAAAA ATCATGAAATACCACCATG TCATGAAATACCACCATGG ATTTGCTGCCTCTGAGGAG GATATACCAAGGACAAAGG CTGCTTGGCCTAAAAGTAC TACAGTACATTCCTTCCCC CCTTCACCCTGCTTGACTT TCAATCAGCAAAGTCTGAA CTGAGGAAGAATTTGAGAT CGCTTGGCCTAAAAGTACA GCAAATTCTGAAATGCATC GCAAATTCTGAAATGCAAC CTCTGAGGAGGGCATTAGA TCTGAGGAGGGCATTAGAA CCACCATGGGGATTCGATC CACCATGGGGATTCGATCA ACCATGGGGATTCGATCAG NNNNNNNNNNNNNNNNTTT NNNNNNNNNNNNNNNTTTC TACAAAATAACACGAGGAA ACGAGGAAAAATTAGTTTC TGATTCAATCAGCAAATTC AACCAAGAATCAACGATAG ACCAAGAATCAACGATAGA CCAAGAATCAACGATAGAA AGCTCTAGGACATACCAAG GAACCATTAGTTACCAGAG TAATCAAGGCTCCCACTCT AAAATTAGTTTCCAGAGCC AAATTAGTTTCCAGAGCCT AAATTAGTTTCCAGAGCCA AATTAGTTTCCAGAGCCTG CTTCACCCTGCTTGACTTA NNNNNNNNNNNNANATTNT NNNNNNNNNNNANATTNTN GGAGATTCAATCAGCAAAT AGGAAGATCATGAAATCCC ACAGTACATTCCTTCCCCG NNNNNNNNNTTTCTGAATG NNNNNNNNTTTCTGAATGT NNNNNNNTTTCTGAATGTT CAAATTCTGAAATGCATCA AGCCAGTTATACTTTGAAA TCAAAATAACACGAGGAAA TTCCCCCTGCTTGGCCTAA TCCCCCTGCTTGGCCTAAA GTTATATTGTTAAAAATCA TTATATTGTTAAAAATCAC TATATTGTTAAAAATCACC CCATTTACCCTGCTTGGCC CATTTACCCTGCTTGGCCT CATGGTGATTCAATCAGCA ATGGTGATTCAATCAGCAA ACCCAAAAACCAAGAATCA CACCATGGGGATTCAATCA ACCATGGGGATTCAATCAG CCATGGGGATTCAATCAGC AAGTTCAAAATAACACGAG TGCTTGGCCTAAAAGGACA CAAGCTCTAGGACATACCA AAGCTCTAGGACATACCAA GGCATTAGAATAGAATAAC GCATTAGAATAGAATAACT GATCATGAAATACCACCAT CATGGGGATTCAATCAGCA CCTCCCACTCTAACTCCCA CATTATCCTTCACACTGCT ATTATCCTTCACACTGCTT TTATCCTTCACACTGCTTG GGATTCAATCAGCAAAGTC AAGTCTGAAATGCAACATT TGAGATGAGGGGACGGATT GAGATGAGGGGACGGATTT AACACGAAGAAAAATTAGT GACAAAGGAAGATCATGAA ACAAAGGAAGATCATGAAA ACATTATCCTTCACACTGC CCCACTCTAACTCCCAAGC ATAGAATATACAGTACATT TAGAATATACAGTACATTC AGAATATACAGTACATTCC ACCAAGGACTAAGGAAGAT CCAAGGACTAAGGAAGATC TACAAAAAAACACGAAGAA CTGAGGAGGGCATTAGAAT TGAGGAGGGCATTAGAATA CATGAAATCCCACCATGGG AAAAGTTCAAAATAACACG AAAGTTCAAAATAACACGA ACCACCATGGGGATTCAAT GGACATACCAAGGACAAAG TAAGGAAGATCATGAAATA TAAAAGTACAAAATAACAC GAAATGCAACATTATCCTT AAATGCAACATTATCCTTC AATGCAACATTATCCTTCA GAATCCACTCAGCAAATTC AATCCACTCAGCAAATTCT AAGGCTCCCACTCTACCTC ACGGATTTGCTGCCTCTGA AAAAGTACAAAAAAACACG CACAGTTGCATCAGCGTAG TCTGAAATGCNNNNNNNNN CTGAAATGCNNNNNNNNNN TGAAATGCNNNNNNNNNNN GAAATGCNNNNNNNNNNNN NNNNNNNNNNANATTNTNA NNNNNNNNNANATTNTNAN GCTTGGCCTAAAAGGACAA CTTGGCCTAAAAGGACAAA ATTAGTTACCAGAGCCTGT TTAGTTACCAGAGCCTGTT GGCTCCCACTCTAACTCCC GACGGATTTGCTGCCTCTG CACACTGCTTGGCCTAAAA ACACTGCTTGGCCTAAAAG CCCAAAGCTAATCAAGGCT CCAAAGCTAATCAAGGCTC GAGCCAATCTGAGGAAGAA CCACTCTACCTCCCAAGCT CCCTGCTTGGTCTAAAAGT CATTAGAATAGAATAACTC ATATACCAAGGACAAAGGA TTCTGAAATGCNNNNNNNN TCCAGAGCCTGTTATATTT AAAGTCTGAAATGCAACAT TAAAAGGACAAAACAACAG GTACAAAAAAACACGAAGA ACAGTTGCATCAGCGTAGA GGCCTAAAAGTACAAAATA TTGGCCTAAAAGGACAAAA CACTCTACCTCCCAAGCTC ACCCTGCTTGGTCTAAAAG TAAAAGTTCAAAATAACAC ACTCGAGGAAAAATTAGTT NNNNNNNNANATTNTNANA NNNNNNNANATTNTNANAA AGCCAGTTATATTGTTAAA CATTAGTTACCAGAGCCTG ACATTATCCTTCACCCCGC ACCCAAAGCTAATCAAGGC
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This graph comes from… GTTCTAGAAAGTTCTTTGC TAGAAAGTTCTTTGCCCTA AGAAAGTTCTTTGCCCTAA GAAAGTTCTTTGCCCTAAA CAGTGAAAATTTGTGCCTA AGTGAAAATTTGTGCCTAC CACGGACGGCCCGCCAGTC ACGGACGGCCCGCCAGTCA GATAGACTCAAGGGACAAA AAATGTGTAATTTCATGAG AATGTGTAATTTCATGAGT ATGTGTAATTTCATGAGTG CAGAAAACTAAGAATCAAG AGAAAACTAAGAATCAAGG GAAAACTAAGAATCAAGGA ACTAAGAATCAAGGATAGA CTAAGAATCAAGGATAGAA TAAGAATCAAGGATAGAAT TAAGAATCAAGGATAGAAG CTCCCCCTAAAGCTTTCAC CTGAGAATCAAGGATAGAA TGAGAATCAAGGATAGAAT TCAAGGATAGAATTTCTAG CAAGGATAGAATTTCTAGA AAGGATAGAATTTCTAGAA CTAAAGCTTTCACAGTTGA TAAAGCTTTCACAGTTGAC TGTGTAATTTCATGAGTGG AAGCTTTCACACTTGCCTC AGCTTTCACACTTGCCTCG AAAGTTCATTCCCCTAAAG AGAATTTCTAGAAAGTTCC TTCTAGAAAGTCCCTCCCC CTCAGTGTATATATGTGGG CTCAGTGTATATATGTGGC GAGTGGGGTCTCCAGTCAT CGGACGGCCCGCCAGTCAT AGTGGGGTCTCCAGTCATT GTGGGGTCTCCAGTCATTA ACATCAGAAAACTGAGAAT CATCAGAAAACTGAGAATC ATCAGAAAACTGAGAATCA AAAGTCCCTCCCCCTAAGG AAGTCCCTCCCCCTAAGGC AGTCCCTCCCCCTAAGGCT CCCGCTGACAGGCCCCCAG CCGCTGACAGGCCCCCAGT CGCTGACAGGCCCCCAGTC GTCTCCAGTCATTAAATTC TCTCCAGTCATTAAATTCA TCATTAAATTCAAGCCCCA CATTAAATTCAAGCCCCAA GCCTAGGAGAAAGCAACAT CCTAGGAGAAAGCAACATG CTAGGAGAAAGCAACATGA ATTCAAGCTCCAAGAAACA TTCAAGCTCCAAGAAACAA TCAAGCTCCAAGAAACAAA GCCTAGGAGATAGCAACAT CCTAGGAGATAGCAACATG CTAGGAGATAGCAACATGA GTGGCTATCCCCCTGAGGG TGGCTATCCCCCTGAGGGG GGCTATCCCCCTGAGGGGC AATTGTAAGAACTGCCCTC ATTGTAAGAACTGCCCTCC TTGTAAGAACTGCCCTCCC GTGTATATTGGTGGCTATC TGTATATTGGTGGCTATCC GTATATTGGTGGCTATCCC GTAATTGTAAGAACTGCCC TAATTGTAAGAACTGCCCT CCCCGTAAAGCTTTCACAC CCCGTAAAGCTTTCACACT CCGTAAAGCTTTCACACTT ACTCCCGGGCCGCCAGTCA CTCCCGGGCCGCCAGTCAT TCCCGGGCCGCCAGTCATT GCCTCAGTGTATATATGAG CCTCAGTGTATATATGAGG CTCAGTGTATATATGAGGC ACTCATCAGAAAACTGAGA CTCATCAGAAAACTGAGAA TCATCAGAAAACTGAGAAT GTCTTTACTGGTGCTCTTC TCTTTACTGGTGCTCTTCC CTTTACTGGTGCTCTTCCC TCCCCCTGACGGCCCGCCA CCCCCTGACGGCCCGCCAG CCCCTGACGGCCCGCCAGT TTTACTGGTGCTCTTCCCA TTACTGGTGCTCTTCCCAC TACTGGTGCTCTTCCCACT GAAAAATCATCAGAAAACT AAAAATCATCAGAAAACTG AAAAATCATCAGAAAACTA AAAATCATCAGAAAACTGA AAAATCATCAGAAAACTAA AGACAAACCCTTGAAAAAA GACAAACCCTTGAAAAAAA ACAAACCCTTGAAAAAAAG CTACCCCACTCCCGGGCCG TACCCCACTCCCGGGCCGC ACCCCACTCCCGGGCCGCC NNTCAGAAAACTGAGAATC NTCAGAAAACTGAGAATCA TCAGAAAACTGAGAATCAA AGTTATACTTTGAAAAATC GTTATACTTTGAAAAATCA TTATACTTTGAAAAATCAT ACACTTGCCTCAGTGTAAA CACTTGCCTCAGTGTAAAT ACTTGCCTCAGTGTAAATA CCCCCAGTCATAAAATTCA CCCCAGTCATAAAATTCAA CCCAGTCATAAAATTCAAG TATCCCACTGACAGGCCGC ATCCCACTGACAGGCCGCC TCCCACTGACAGGCCGCCA GAAAGTTCCTCCCCCTAAA AAAGTTCCTCCCCCTAAAG AAGTTCCTCCCCCTAAAGC TGACAGGCCCCCAGTCATT GACAGGCCCCCAGTCATTA ACAGGCCCCCAGTCATTAA GGCATTAAATTCAAGCTCC GCATTAAATTCAAGCTCCA CATTAAATTCAAGCTCCAA AGCTTTCACTCTTGCCTCA GCTTTCACTCTTGCCTCAG CTTTCACTCTTGCCTCAGT AAAAGCCAGCCTAGGAGAA AAAGCCAGCCTAGGAGAAA AAGCCAGCCTAGGAGAAAG AAGGGACAAAGCAGTAAAA AGGGACAAAGCAGTAAAAT GGGACAAAGCAGTAAAATG ACTCTTGCCTCAGTGTATA CTCTTGCCTCAGTGTATAT TCTTGCCTCAGTGTATATA CCTCGGAGAAAGCAACATG CTCGGAGAAAGCAACATGA TCGGAGAAAGCAACATGAT GCTTTCACACTTGCCTCAG CTTTCACACTTGCCTCAGT TTTCACACTTGCCTCAGTG CCGGACCCCCAGTCATAAA CGGACCCCCAGTCATAAAA GGACCCCCAGTCATAAAAT TTTGCCCTAAAGATTTCAC TTGCCCTAAAGATTTCACA TGCCCTAAAGATTTCACAC CAAGGGACAAAGCAGTAAA GCCAGTTATATTTTGAAAA CCAGTTATATTTTGAAAAA CAGTTATATTTTGAAAAAT ATACTTTGAAAAATCATCA TACTTTGAAAAATCATCAG ACTTTGAAAAATCATCAGA AAAATGTGTAATTTCATGA CCACTCCCGGGCCGCCAGT CACTCCCGGGCCGCCAGTC TAGAAAGTTCCTTCCCCTA AGAAAGTTCCTTCCCCTAA GAAAGTTCCTTCCCCTAAA AGGCTATACCACTGACGGG GGCTATACCACTGACGGGC GCTATACCACTGACGGGCC ATGCAAGCTCCAAGAGACA TGCAAGCTCCAAGAGACAA GCAAGCTCCAAGAGACAAA CATTAAATTCAACCACCAA ATTAAATTCAACCACCAAG TTAAATTCAACCACCAAGA ATCAAGGATAGACTTTCTA TCAAGGATAGACTTTCTAG CAAGGATAGACTTTCTAGA TTCAACCCTGGCCTCAGTG TCAACCCTGGCCTCAGTGT CAACCCTGGCCTCAGTGTA TGAAAAATCATCAGAAAAC CCCACTCCCGGGCCGCCAG CACACTTGCCTAGGTGAAT ACACTTGCCTAGGTGAATA CACTTGCCTAGGTGAATAT GTATATATGGGGCTATACC TATATATGGGGCTATACCA ATATATGGGGCTATACCAC CCTTTGACAGGCCGCCAGT CTTTGACAGGCCGCCAGTC TTTGACAGGCCGCCAGTCA AGCTTCCACACTTGCCTCA GCTTCCACACTTGCCTCAG CTTCCACACTTGCCTCAGT TCATGAGTGGGGTCTCCAG CATGAGTGGGGTCTCCAGT ATGAGTGGGGTCTCCAGTC CTTTGAAAAATCATCAGAA CCCCCTAAAGCTTCAACCC CCCCTAAAGCTTCAACCCT CCCTAAAGCTTCAACCCTG CAGGCATTAAATTCAAGCT AGGCATTAAATTCAAGCTC AAATGTGATTTGCCCAGGA AATGTGATTTGCCCAGGAG ATGTGATTTGCCCAGGAGG AGGGGCCGCCAGTCATTAA GGGGCCGCCAGTCATTAAA GGGCCGCCAGTCATTAAAT CCACTTCCCTCAGTGTATA CACTTCCCTCAGTGTATAT ACTTCCCTCAGTGTATATA GTGGCTATCCCACTGACGG TGGCTATCCCACTGACGGG GGCTATCCCACTGACGGGC AGCCCCAAGAGACAAACCC GCCCCAAGAGACAAACCCT CCCCAAGAGACAAACCCTT CTAGGAGAAAGAAACATGA TAGGAGAAAGAAACATGAT AGGAGAAAGAAACATGATT TTTTGGAAAAAAAGGCAGC TTTGGAAAAAAAGGCAGCC TTGGAAAAAAAGGCAGCCT TTCCTCCCCCTAAAGCTTT TCCTCCCCCTAAAGCTTTC CCTCCCCCTAAAGCTTTCA AGAAACAAACTCTTGAAAA GAAACAAACTCTTGAAAAA AAACAAACTCTTGAAAAAA ACTGGTGCTCTTCCCACTT CAGGCCGCCAGTCATTAAA AGGCCGCCAGTCATTAAAT GGCCGCCAGTCATTAAATT CATTAAATGCAAGCTCCAA ATTAAATGCAAGCTCCAAG TTAAATGCAAGCTCCAAGA CCCAAGAGACAAACCCTTG GAAAATTTGTGCCTACCCC AAAATTTGTGCCTACCCCA AAATTTGTGCCTACCCCAC AAGAATCAAGGATAGAATT AGAATCAAGGATAGAATTT GAATCAAGGATAGAATTTC ACCACCGACGGCCCGCCAG CCACCGACGGCCCGCCAGG CACCGACGGCCCGCCAGGC CACACTTGCCTCGGTGTAT ACACTTGCCTCGGTGTATA CACTTGCCTCGGTGTATAT GAGGCTATACCACTGACGG AAAGAGACAAACTCTTGAA AAGAGACAAACTCTTGAAA AGAGACAAACTCTTGAAAA GGCAGCCTAGGAGAAAGCA GCAGCCTAGGAGAAAGCAA CAGCCTAGGAGAAAGCAAC AGTGTATATATGTGGCTAT GTGTATATATGTGGCTATA GTGTATATATGTGGCTATC TGTATATATGTGGCTATAC TGTATATATGTGGCTATCC TCTAGAAAGTACCTTCCCC CTAGAAAGTACCTTCCCCT TAGAAAGTACCTTCCCCTA TATAGGTGGGTATCCCGCT ATAGGTGGGTATCCCGCTG TAGGTGGGTATCCCGCTGA TTTCCCACTTCCCTCAGTG TTCCCACTTCCCTCAGTGT TCCCACTTCCCTCAGTGTA GGATAGAAGTTCTAGAAAG GATAGAAGTTCTAGAAAGT ATAGAAGTTCTAGAAAGTT CAAAGCAGTAAAATGTGTA AAAGCAGTAAAATGTGTAA AAGCAGTAAAATGTGTAAT TAAAATGTGTAATTTCATG GCCTAGGTGAATATAGGTG CCTAGGTGAATATAGGTGG CTAGGTGAATATAGGTGGG GCCTGTTATATTTTGAAAA CCTGTTATATTTTGAAAAC CCTGTTATATTTTGAAAAA CTGTTATATTTTGAAAACT CTGTTATATTTTGAAAAAA CTGTTATATTTTGAAAAAT TTGACAGGCCGCCAGTCAT TGACAGGCCGCCAGTCATT GACAGGCCGCCAGTCATTA TAGAATTTCTAGAAATTTC AGAATTTCTAGAAATTTCC GAATTTCTAGAAATTTCCT AGGAGGGGGCGTCCAGTCA GGAGGGGGCGTCCAGTCAT AGGAGAAAGCAGCATGATT GGAGAAAGCAGCATGATTA GAGAAAGCAGCATGATTAT GGCCCGCCAGTCATTAAAT GCCCGCCAGTCATTAAATT CCCGCCAGTCATTAAATTC TGTAAGAACTGCCCTCCCC ATGTGCCTATACCACGGAC TGTGCCTATACCACGGACG GTGCCTATACCACGGACGG CCACCAAGAGACAAACTCT CACCAAGAGACAAACTCTT ACCAAGAGACAAACTCTTG TAAAGATTTCACACTTGTG AAAGATTTCACACTTGTGT AAGATTTCACACTTGTGTC CTTTCCCACTTCCCTCAGT TTNTNANAAATNNTCAGAA TNTNANAAATNNTCAGAAA NTNANAAATNNTCAGAAAA CCTAAAGATTTCACACTTG CTAAAGATTTCACACTTGT AAAGAAACATGATTTTTCA TAAATTCAACCACCAAGAG AAATTCAACCACCAAGAGA TGGCTATTCCTTTGACAGG GGCTATTCCTTTGACAGGC GCTATTCCTTTGACAGGCC CCTTCCCCTAAAGCTTTCA CTTCCCCTAAAGCTTTCAC TTCCCCTAAAGCTTTCACT TTCCCCTAAAGCTTTCACA AAGCTTTCACTCTTGCCTC TGCTCTTCCCACTTCCGGA GCTCTTCCCACTTCCGGAC CTCTTCCCACTTCCGGACC CCCCTGACAGGCCGCCAGT CCCTGACAGGCCGCCAGTC CCTGACAGGCCGCCAGTCA TATATTTTGAAAAAACATC ATATTTTGAAAAAACATCA TATTTTGAAAAAACATCAG ACTGGCCTCAGTGTATATA CTGGCCTCAGTGTATATAT TGGCCTCAGTGTATATATG ACAGGCCGCCAGTCATTAA CTAGAAATTTCCTTCCCCT TAGAAATTTCCTTCCCCTA AGAAATTTCCTTCCCCTAA CTTTCACACTGGCCTCAGT TTTCACACTGGCCTCAGTG TTCACACTGGCCTCAGTGT CCCACTGACAGGCCGCCAG CCACTGACAGGCCGCCAGT GCTGACAGGCCCCCAGTCA CTGACAGGCCCCCAGTCAT AACTCATCAGAAAACTGAG CCCTAAAGATTTCACACTT TCACACTGGCCTCAGTGTA NTTTCTGAATGTTTCTTAG AGAAAGTCCCTCCCCCTAA GAAAGTCCCTCCCCCTAAG CAGTCATTAAATTCAAACT AGTCATTAAATTCAAACTC GTCATTAAATTCAAACTCC ATGTGGCTATACCACTTAC TGTGGCTATACCACTTACG GTGGCTATACCACTTACGG GGGCGTCCAGTCATTAAAT GGCGTCCAGTCATTAAATT GCGTCCAGTCATTAAATTC ACGGCCCGCCAGTCATTAA CGGCCCGCCAGTCATTAAA CTCCAAGAGACAAACCCTT TCCAAGAGACAAACCCTTG CCAAGAGACAAACCCTTGA CTATTCCTTTGACAGGCCG CTCCCCGTAAAGCTTTCAC TCCCCGTAAAGCTTTCACA CAAGCTCCAAGAGACAAAC CTCCCCCTAAGGCTTTCAC TCCCCCTAAGGCTTTCACA CCCCCTAAGGCTTTCACAC CTAGAAAGTTCCTTCCCCT CAATATATGTGACTACACC AATATATGTGACTACACCA ATATATGTGACTACACCAC ATTAAATTCAAGCTCCAAG TTAAATTCAAGCTCCAAGA TAAATTCAAGCTCCAAGAG TAAATTCAAGCTCCAAGAA TAAATTCAAACTCCAAGAG AAATTCAAACTCCAAGAGA AATTCAAACTCCAAGAGAC GTGGCTATACCACTGACAG TGGCTATACCACTGACAGG GGCTATACCACTGACAGGC TGTGATTTGCCCAGGAGGG TCTAGAAAGTCCCTCCCCC CTAGAAAGTCCCTCCCCCT TAGAAAGTCCCTCCCCCTA TCAAAGAGACAAACTCTTG CAAAGAGACAAACTCTTGA AGGCAGCCTAGGAGAAAGA GGCAGCCTAGGAGAAAGAA GCAGCCTAGGAGAAAGAAA AAGCTCCAAGAGACAAACC AAGCTCCAAGAGACAAACT AGCTCCAAGAGACAAACCC AGCTCCAAGAGACAAACTC CATTAAATTCAAACTCCAA ATTAAATTCAAACTCCAAG TTAAATTCAAACTCCAAGA AAACTGAGAATCAAGGATA AACTGAGAATCAAGGATAG ACTGAGAATCAAGGATAGA TTGAAAAAAAGCCAGCCTA TGAAAAAAAGCCAGCCTAG GAAAAAAAGCCAGCCTAGG CTTGCCTCAGTGTATATAT TTGCCTCAGTGTATATATG TGCCTCAGTGTATATATGG TGCCTCAGTGTATATATGT TGCCTCAGTGTATATATGA AAAGCAACCGGATTTTTCA TAGAAAGTTCATTCCCCTA AGAAAGTTCATTCCCCTAA GAAAGTTCATTCCCCTAAA GACAAGTTTTGGAAAAAAA ACAAGTTTTGGAAAAAAAG CAAGTTTTGGAAAAAAAGG AATTTCTAGAAAGTTCCTT ATTTCTAGAAAGTTCCTTC TTTCTAGAAAGTTCCTTCC TTCCCACTTCCGGACCCCC TCCCACTTCCGGACCCCCA CCCACTTCCGGACCCCCAG ACTTGCCTCGGTGTATATA CTTGCCTCGGTGTATATAT AGCTTCAACCCTGGCCTCA GCTTCAACCCTGGCCTCAG CTTCAACCCTGGCCTCAGT AACAAATGTGATTTGCCCA ACAAATGTGATTTGCCCAG CAAATGTGATTTGCCCAGG AGACAAGTTTTGGAAAAAA TTATATATGTGGCTATCCC TATATATGTGGCTATCCCA ATATATGTGGCTATCCCAC TCAAGCTCCAAGAGACAAA TCCGAGGAGAAAGCAACCG CCGAGGAGAAAGCAACCGG CGAGGAGAAAGCAACCGGA ATGTGGGTATACCACTGAC TGTGGGTATACCACTGACA GTGGGTATACCACTGACAG ATGAGGCTATACCACTGAC TGAGGCTATACCACTGACG ACACTTGCCACAGTGAAAA CACTTGCCACAGTGAAAAT ACTTGCCACAGTGAAAATT TCTTGAAAAAAAGGCAGCC CTTGAAAAAAAGGCAGCCT TTGAAAAAAAGGCAGCCTA TTGAAAAAAAGGCAGCCTC GGCCTCAGTGTATATATGT GCCTCAGTGTATATATGTG CTGAGGGGCCGCCAGTCAT TGAGGGGCCGCCAGTCATT GAGGGGCCGCCAGTCATTA AATTTCCTTCCCCTAAACC ATTTCCTTCCCCTAAACCT TTTCCTTCCCCTAAACCTT CAAGAGACAAACCCTTGAA TGTATATATGAGGCTATAC GTATATATGAGGCTATACC TATATATGAGGCTATACCA TATTGGTGGCTATCCCCCT ATTGGTGGCTATCCCCCTG TTGGTGGCTATCCCCCTGA TAAAGCTTTCCCACTTCCC AAAGCTTTCCCACTTCCCT AAGCTTTCCCACTTCCCTC CCAAGAAACAAACTCTTGA CAAGAAACAAACTCTTGAA AAGAAACAAACTCTTGAAA TCCCGCTGACAGGCCCCCA TATGAGGCTATACCACTGA AGAAAGCAGCATGATTATT TTCCACACTTGCCTCAGTG CAAGCTCAAAGAGACAAAC AAGCTCAAAGAGACAAACT AGCTCAAAGAGACAAACTC GTATATATGTGGCTATACC TATATATGTGGCTATACCA ATATATGTGGCTATACCAC TTCTTTGCCCTAAAGATTT TCTTTGCCCTAAAGATTTC CTTTGCCCTAAAGATTTCA AAAGTTCCTTCCCCTAAAG AAGTTCCTTCCCCTAAAGC AGTTCCTTCCCCTAAAGCT ATATGTGCCTATACCACGG TATGTGCCTATACCACGGA TNNTCAGAAAACTGAGAAT TATATATGTGGGTATACCA ATATATGTGGGTATACCAC TATATGTGGGTATACCACT CACTGACGGGCCGCCAGTC ACTGACGGGCCGCCAGTCC ACTGACGGGCCGCCAGTCA CTGACGGGCCGCCAGTCCT CTGACGGGCCGCCAGTCAT AGTTCCTCCCCCTAAAGCT GTTCCTCCCCCTAAAGCTT CCACACTTGCCTCAGTGTA CACACTTGCCTCAGTGTAA AGGTGGGTATCCCGCTGAC CCACTTCCGGACCCCCAGT CACTTCCGGACCCCCAGTC CCCTTGCCTCAGTGTATAT CCTTGCCTCAGTGTATATA AAAAAAAGGCAGCCTCGGA AAAAAAGGCAGCCTCGGAG AAAAAGGCAGCCTCGGAGA TAAAGCTTTCACTCTTGCC AAAGCTTTCACTCTTGCCT CTAAAGCTTCAACCCTGGC TAAAGCTTCAACCCTGGCC AAAGCTTCAACCCTGGCCT GAGAAAGCAACATGATTTT AGAAAGCAACATGATTTTT GAAAGCAACATGATTTTTC GTGGCTATCCCCCTGACGG TGGCTATCCCCCTGACGGC GGCTATCCCCCTGACGGCC GTAAAGCTTTCACACTTGC TAAAGCTTTCACACTTGCC AAAGCTTTCACACTTGCCT TTCTAGAAAGTTCTTTGCC TCTAGAAAGTTCTTTGCCC CTAGAAAGTTCTTTGCCCT ACGGCCCGCCAGGCATTAA CGGCCCGCCAGGCATTAAA GGCCCGCCAGGCATTAAAT CAGTGTATATATGAGGCTA AGTGTATATATGAGGCTAT GTGTATATATGAGGCTATA ATATGTGGGTATACCACTG TATGTGGGTATACCACTGA ATTCAACCACCAAGAGACA TTCAACCACCAAGAGACAA TCAACCACCAAGAGACAAA TGAAAAAAAGGCAGCCTCG GAAAAAAAGGCAGCCTCGG GCTCCAAGAGACAAACTCT CTCCAAGAGACAAACTCTT CCCTAAAGCTTCCACACTT CCTAAAGCTTCCACACTTG CTAAAGCTTCCACACTTGC AGCTTCCACACTTGCCTAG GCTTCCACACTTGCCTAGG CTTCCACACTTGCCTAGGT CACTGGCCTCAGTGTATAT ATTTCATGAGTGGGGTCTC TTTCATGAGTGGGGTCTCC TTCATGAGTGGGGTCTCCA AGGATAGAATTTCTAGAAA ACTCAAGGGACAAAGCAGT CTCAAGGGACAAAGCAGTA TCAAGGGACAAAGCAGTAA CCTGAGGGGCCGCCAGTCA AAAAAAAGCCAGCCTAGGA GGGGCTATACCACTGACAG GGGCTATACCACTGACAGG AAATTTCCTTCCCCTAAAC GTAAAATGTGTAATTTCAT AGATTTCACACTTGTGTCA TCAAGCTCCAAGAGACAAG CAAGCTCCAAGAGACAAGT AAGCTCCAAGAGACAAGTT GCCAGTTATACTTTGAAAA CCAGTTATACTTTGAAAAA CAGTTATACTTTGAAAAAT CCAAGAGACAAGTTTTGGA CAAGAGACAAGTTTTGGAA AAGAGACAAGTTTTGGAAA AAGCTCCAAGAAACAAACT AGCTCCAAGAAACAAACTC GCTCCAAGAAACAAACTCT TAGAATTTCTAGAAAGTCC AGAATTTCTAGAAAGTCCC GAATTTCTAGAAAGTCCCT GTATACCACTGACAGGCCG TATACCACTGACAGGCCGC ATACCACTGACAGGCCGCC ACCACGGACAGGCCGCCAG CCACGGACAGGCCGCCAGT CACGGACAGGCCGCCAGTC AAAATTCAAGCTCCAAGAG AAATTCAAGCTCCAAGAGA AATTCAAGCTCCAAGAGAC GTGTAATTTCATGAGTGGG TGTAATTTCATGAGTGGGG GTAATTTCATGAGTGGGGT AACTGCCCTCCCCCTAAAG ACTGCCCTCCCCCTAAAGC CTGCCCTCCCCCTAAAGCT CCCTTAAAGCTTCCACACT CCTTAAAGCTTCCACACTT CTTAAAGCTTCCACACTTG AGCCTCGGAGAAAGCAACA GCCTCGGAGAAAGCAACAT AGAAAGTACCTTCCCCTAA ACTTCCGGACCCCCAGTCA CTTCCGGACCCCCAGTCAT TTCCGGACCCCCAGTCATA ATAGCAACATGATTTTTCA GAGACAAACCCTTGAAAAA TTTGTGCCTACCCCACTCC TTGTGCCTACCCCACTCCC TGTGCCTACCCCACTCCCG AGTTCATTCCCCTAAAGCC GTTCATTCCCCTAAAGCCT TTCATTCCCCTAAAGCCTT AAATCATCAGAAAACTAAG AATCATCAGAAAACTAAGA ATCATCAGAAAACTAAGAA TGGCTATACCACTTACGGG AATTTGTGCCTACCCCACT ATTTGTGCCTACCCCACTC CCGCCAGGCATTAAATTCA CGCCAGGCATTAAATTCAA GCCAGGCATTAAATTCAAG AGCTCCAAGAGACAAGTTT GCTCCAAGAGACAAGTTTT CTCCAAGAGACAAGTTTTG TATTCCTTTGACAGGCCGC ATTCCTTTGACAGGCCGCC CAGTGTATATTGGTGGCTA AGTGTATATTGGTGGCTAT TACCACTGACAGGCCGCCA ACCACTGACAGGCCGCCAG ACGGGCCGCCAGTCATTAA CGGGCCGCCAGTCATTAAA GAAAAAAAGGCAGCCTAGG AAAAAAAGGCAGCCTAGGC AAAAAAAGGCAGCCTAGGA AAAAAAGGCAGCCTAGGCG AAAAAAGGCAGCCTAGGAG CAGCCTCGGAGAAAGCAAC TCAAACTCCAAGAGACAAA CAAACTCCAAGAGACAAAC AAACTCCAAGAGACAAACT CTATCCCCCTGACGGCCCG TATCCCCCTGACGGCCCGC ATCCCCCTGACGGCCCGCC GTGATTTGCCCAGGAGGGG TGATTTGCCCAGGAGGGGG GATTTGCCCAGGAGGGGGC ACCTTTCACACTTGCCTCA CCTTTCACACTTGCCTCAG TCAGTGTATATATGAGGCT CCAAGAGACAAACTCTTGA AGTTATATTTTGAAAAATC GTTATATTTTGAAAAATCA TTATATTTTGAAAAATCAT AAGCTTCAACCCTGGCCTC GGACGGCCCGCCAGTCATT GACGGCCCGCCAGTCATTA AAGGCAGCCTCGGAGAAAG AGGCAGCCTCGGAGAAAGC GGCAGCCTCGGAGAAAGCA CCACAGTGAAAATTTGTGC CACAGTGAAAATTTGTGCC ACAGTGAAAATTTGTGCCT GAAAGTACCTTCCCCTAAA AAAGTACCTTCCCCTAAAG GTTCCTTCCCCTAAAGCTT TTCCTTCCCCTAAAGCTTT ACTTGCCTAGGTGAATATA TCCTTCCCCTAAAGCTTTC GAAGATAGACTCAAGGGAC AAGATAGACTCAAGGGACA AGATAGACTCAAGGGACAA AATNNTCAGAAAACTGAGA ATNNTCAGAAAACTGAGAA TTCACTCTTGCCTCAGTGT TCACTCTTGCCTCAGTGTA CACTCTTGCCTCAGTGTAT AGGTGGCTATTCCTTTGAC GGTGGCTATTCCTTTGACA GTGGCTATTCCTTTGACAG AAGGATAGACTTTCTAGAA GGTGGGTATCCCGCTGACA GTGGGTATCCCGCTGACAG AAGTTTTGGAAAAAAAGGC AGTTTTGGAAAAAAAGGCA GTTTTGGAAAAAAAGGCAG TTGCCTAGGTGAATATAGG TGCCTAGGTGAATATAGGT NNNNNNANATTNTNANAAA NNNNNANATTNTNANAAAT NNNNANATTNTNANAAATN TCAGTGTATATATGGGGCT CAGTGTATATATGGGGCTA AGTGTATATATGGGGCTAT AGGATAGACTTTCTAGAAA GGATAGACTTTCTAGAAAG TCCCCCTAAAGCTTTCACA CCCCCTAAAGCTTTCACAC CCCCTAAAGCTTTCACACT GCGCGAACCCACGGACAGG CGCGAACCCACGGACAGGC GCGAACCCACGGACAGGCC TGGGTATACCACTGACAGG GGGTATACCACTGACAGGC TGCCTATACCACGGACGGC GCCTATACCACGGACGGCC CAGAAAACTGAGAATCAAG GTGCCTACCCCACTCCCGG ATTCAAACTCCAAGAGACA TTCAAACTCCAAGAGACAA TGGAAAAAAAGGCAGCCTA GGAAAAAAAGGCAGCCTAG TCATTAAATTCAAGCTCCA TCCGGACCCCCAGTCATAA GCTTTCACACTTGCCTCGG CTTTCACACTTGCCTCGGT TTTCACACTTGCCTCGGTG CTTCCCTCAGTGTATATAT TTCCCTCAGTGTATATATG TCCCTCAGTGTATATATGT GTGAAAATTTGTGCCTACC TGAAAATTTGTGCCTACCC GGTATACCACTGACAGGCC AATGCAAGCTCCAAGAGAC AACCCTGGCCTCAGTGTAT ACCCTGGCCTCAGTGTATA CCCTGGCCTCAGTGTATAT AGTACCTTCCCCTAAAGCT GTACCTTCCCCTAAAGCTT TACCTTCCCCTAAAGCTTT ATACCACGGACGGCCCGCC TACCACGGACGGCCCGCCA ACCACGGACGGCCCGCCAG CCCACTGACGGGCCGCCAG CCACTGACGGGCCGCCAGT GCCGCCAGTCATTAAATTC CCGCCAGTCATTAAATTCA CGCCAGTCATTAAATTCAA ATTTTGAAAAAACATCAGA TTTTGAAAAAACATCAGAA TTTGAAAAAACATCAGAAA GAAAAAACATCAGAAAACT AAAAAACATCAGAAAACTG AAAAACATCAGAAAACTGA GTCATTAAATTCAACCACC TCATTAAATTCAACCACCA GGACAAAGCAGTAAAATGT CTATACCACTTACGGGCCG TATACCACTTACGGGCCGC ATACCACTTACGGGCCGCC TCATTAAATTCAAACTCCA AATATAGGTGGGTATCCCG ATATAGGTGGGTATCCCGC CCTGGCCTCAGTGTATATA GAGAAAGCAACCGGATTTT AGAAAGCAACCGGATTTTT GAAAGCAACCGGATTTTTC ATAGATTTTCTAGAAAGTT TAGATTTTCTAGAAAGTTC AGATTTTCTAGAAAGTTCC GATAGACTTTCTAGAAAGT GTATATATGTGGGTATACC CCTAAAGCTTCAACCCTGG CCCCTAAAGCTTTCACAGT CCCTAAAGCTTTCACAGTT CCTAAAGCTTTCACAGTTG TCCAAGAGACAAACTCTTG TCCCCTAAAGCTTTCACTC CCCCTAAAGCTTTCACTCT CCCTAAAGCTTTCACTCTT AGAATTTCTAGAAAGTTCA GAATTTCTAGAAAGTTCAT AATTTCTAGAAAGTTCATT ATTTTCTAGAAAGTTCCTT TTTTCTAGAAAGTTCCTTC AAGAATCAAGGATAGAAGT CTCAGTGTATATTGGTGGC TCAGTGTATATTGGTGGCT GCTATCCCCCTGACGGCCC TAAAGCTTCCACACTTGCC CTTGAAAAAAAGCCAGCCT CAGTAAAATGTGTAATTTC AGTAAAATGTGTAATTTCA NNNANATTNTNANAAATNN NNANATTNTNANAAATNNT NANATTNTNANAAATNNTC CCTAGGAGAAAGAAACATG TCTTCCCACTTCCGGACCC CTTCCCACTTCCGGACCCC TNANAAATNNTCAGAAAAC NANAAATNNTCAGAAAACT ANAAATNNTCAGAAAACTG GACGGGCCGCCAGTCCTTA ACGGGCCGCCAGTCCTTAA CGGGCCGCCAGTCCTTAAA TGTAAATATGTGGCTATAC GTAAATATGTGGCTATACC TAAATATGTGGCTATACCA CCCTGACGGCCCGCCAGTC CCTGACGGCCCGCCAGTCA CTGACGGCCCGCCAGTCAT CTACACCACCGACGGCCCG TACACCACCGACGGCCCGC ACACCACCGACGGCCCGCC TCATTCCCCTAAAGCCTTC CATTCCCCTAAAGCCTTCA ATTCCCCTAAAGCCTTCAC TGTTATATTTTGAAAACTC GTTATATTTTGAAAACTCA ATTAAATTCAAGCCCCAAG TTAAATTCAAGCCCCAAGA TAAATTCAAGCCCCAAGAG CCCCTAAAGCTTCCACACT GGATAGATTTTCTAGAAAG GATAGATTTTCTAGAAAGT GCTATACCACTGACAGGCC ACTCTTGAAAAAAAGGCAG CTCTTGAAAAAAAGGCAGC CACACTTGCCTCAGTGTAT ACACTTGCCTCAGTGTATA CACTTGCCTCAGTGTATAT CAGTCTTTACTGGTGCTCT AGTCTTTACTGGTGCTCTT ATGTAACAAATGTGATTTG TGTAACAAATGTGATTTGC GTAACAAATGTGATTTGCC AAAAGGCAGCCTCGGAGAA AAAGGCAGCCTCGGAGAAA GATAGAATTTCTAGAAAGT ATAGAATTTCTAGAAAGTT TAGAATTTCTAGAAAGTTC AAGTACCTTCCCCTAAAGC CAAGAGACAAACTCTTGAA GCTATCCCCCTGAGGGGCC CTATCCCCCTGAGGGGCCG TCCAGTCATTAAATTCAAG CCAGTCATTAAATTCAAGC CAGTCATTAAATTCAAGCC CAGTCATTAAATTCAAGCT CCCACGGACAGGCCGCCAG AACTCTTGAAAAAAAGGCA TTCCACACTTGCCTAGGTG TCCACACTTGCCTAGGTGA CCCCTAAGGCTTTCACACT CCCTAAGGCTTTCACACTT CTTGCCTCAGTGTAAATAT TTGCCTCAGTGTAAATATG TGCCTCAGTGTAAATATGT CTCTTGAAAAAAAGCCAGC TCTTGAAAAAAAGCCAGCC AACCACCAAGAGACAAACT ACCACCAAGAGACAAACTC TGGCTATCCCCCTGACAGG GGCTATCCCCCTGACAGGC GCTATCCCCCTGACAGGCC AGCTTTCACACTTGCCTCA TATACTTTGAAAAATCATC CTTGCCTAGGTGAATATAG TTGAAAAAACATCAGAAAA TGAAAAAACATCAGAAAAC TACCACTTACGGGCCGCCA GCCCTAAAGATTTCACACT GCCGCCAGTCATTAAATGC CCGCCAGTCATTAAATGCA CGCCAGTCATTAAATGCAA GAAATTTCCTTCCCCTAAA TTGCCCAGGAGGGGGCGTC TGCCCAGGAGGGGGCGTCC GCCCAGGAGGGGGCGTCCA AACAAACTCTTGAAAAAAA ACAAACTCTTGAAAAAAAG AAATCATCAGAAAACTGAG TCCCCTAAAGCTTTCACAC TCCCCTAAAGCTTTCACAG CTGGTGCTCTTCCCACTTC TGGTGCTCTTCCCACTTCC TCCAAGAAACAAACTCTTG AAGCTTCCACACTTGCCTA AAAGCAACATGATTTTTCT AAAGCAACATGATTTTTCA GACGGGCCGCCAGTCATTA GGGGGCGTCCAGTCATTAA GGGGCGTCCAGTCATTAAA GGAGATAGCAACATGATTT GAGATAGCAACATGATTTT AGATAGCAACATGATTTTT TAGGAGAAAGCAGCATGAT TGCCCTCCCCCTAAAGCTT GCCCTCCCCCTAAAGCTTC CCCTCCCCCTAAAGCTTCA TGGGGTCTCCAGTCATTAA GGGGTCTCCAGTCATTAAA GGGTATCCCGCTGACAGGC GGTATCCCGCTGACAGGCC GTATCCCGCTGACAGGCCC AAAGTTCTTTGCCCTAAAG AAGTTCTTTGCCCTAAAGA AGTTCTTTGCCCTAAAGAT GCCCGCCAGGCATTAAATT GCCTCAGTGTATATATGGG CCTCAGTGTATATATGGGG CTCAGTGTATATATGGGGC ACCTTCCCCTAAAGCTTTC AGCCAGCCTAGGAGAAAGC GGCCGCCAGTCATTAAATG CAGCCTAGGAGATAGCAAC AGCCTAGGAGATAGCAACA GAGGGGGCGTCCAGTCATT AGGGGGCGTCCAGTCATTA ATTTTGAAAACTCATCAGA TTTTGAAAACTCATCAGAA TTTGAAAACTCATCAGAAA ATTTGCCCAGGAGGGGGCG TTTGCCCAGGAGGGGGCGT AAATTCAAGCTCCAAGAAA AATTCAAGCTCCAAGAAAC GGACAGGCCGCCAGTCATT AACTCCAAGAGACAAACTC ACTCCAAGAGACAAACTCT GCTATCCCACTGACGGGCC CTATCCCACTGACGGGCCG TATCCCACTGACGGGCCGC CAGGCCCCCAGTCATTAAA CGTAAAGCTTTCACACTTG TAATTTCATGAGTGGGGTC AATTTCATGAGTGGGGTCT GGGCCGCCAGTCCTTAAAT ATGTGGCTATCCCACTGAC TGTGGCTATCCCACTGACA TGTGGCTATCCCACTGACG GTGGCTATCCCACTGACAG GCTATACCACTTACGGGCC ACAAAGCAGTAAAATGTGT TATATGTGGCTATACCACT ATATGTGGCTATACCACTG ATATGTGGCTATACCACTT ATCCCGCTGACAGGCCCCC GTTCTTTGCCCTAAAGATT CAGCCTAGGAGAAAGAAAC AGAATCAAGGATAGAAGTT TCCAAGAGACAAGTTTTGG GTATATATGTGGCTATCCC TATATATGTGGCTATCCCC ATATATGTGGCTATCCCCC TGACGGGCCGCCAGTCATT CTTGCCACAGTGAAAATTT TTGCCACAGTGAAAATTTG TGCCACAGTGAAAATTTGT CCCTCAGTGTATATATGTG CCTCAGTGTATATATGTGG AAAACTAAGAATCAAGGAT AAACTAAGAATCAAGGATA AACTAAGAATCAAGGATAG GATAGCAACATGATTTTTC GCCTCAGTGTAAATATGTG CCTCAGTGTAAATATGTGG CACTGACAGGCCGCCAGTC ACTGACAGGCCGCCAGTCA CTGACAGGCCGCCAGTCAT CCCTGAGGGGCCGCCAGTC CCTATACCACGGACGGCCC CTATACCACGGACGGCCCG ATGTGACTACACCACCGAC TGTGACTACACCACCGACG GTGACTACACCACCGACGG TTCCTTTGACAGGCCGCCA TCCTTTGACAGGCCGCCAG AGAGACAAGTTTTGGAAAA ANATTNTNANAAATNNTCA AATCAAGGATAGAATTTCT CCCACTTCCCTCAGTGTAT TATCCCGCTGACAGGCCCC TTAACACTTGCCACAGTGA TAACACTTGCCACAGTGAA AACACTTGCCACAGTGAAA CTCCAGTCATTAAATTCAA TATACCACGGACGGCCCGC NNNNNNTTTCTGAATGTTT NNNNNTTTCTGAATGTTTC NNNNTTTCTGAATGTTTCT GTCATTAAATTCAAGCTCA TCATTAAATTCAAGCTCAA CATAAAATTCAAGCTCCAA CATTAAATTCAAGCTCAAA ATAAAATTCAAGCTCCAAG TAAAATTCAAGCTCCAAGA CTATCCCCCTGACAGGCCG TATCCCCCTGACAGGCCGC CACTTACGGGCCGCCAGTC ACTTACGGGCCGCCAGTCA CTTACGGGCCGCCAGTCAT TGTTATATTTTGAAAAATC GAATCAAGGATAGACTTTC AATCAAGGATAGACTTTCT AGGAGAAAGCAACATGATT GGAGAAAGCAACATGATTT NAAATNNTCAGAAAACTGA AAATNNTCAGAAAACTGAG GGCTATACCACTTACGGGC CATCAGAAAACTAAGAATC ATCAGAAAACTAAGAATCA TCAGAAAACTAAGAATCAA TTCCTTCCCCTAAACCTTT TCCTTCCCCTAAACCTTTC CCTTCCCCTAAACCTTTCA TGGCTATCCCACTGACAGG AATTTCTAGAAATTTCCTT ATATATGAGGCTATACCAC CCCGGGCCGCCAGTCATTA CCGGGCCGCCAGTCATTAA GAATATAGGTGGGTATCCC GCTTTAACACTTGCCACAG CTTTAACACTTGCCACAGT TTTAACACTTGCCACAGTG GAAAACTGAGAATCAAGGA AAAACTGAGAATCAAGGAT CAGTCATTAAATTCAACCA AGTCATTAAATTCAACCAC CTCCAAGAAACAAACTCTT AACCTTTCACACTTGCCTC CGCAGCCTAGGAGATAGCA GCAGCCTAGGAGATAGCAA AAAACATCAGAAAACTGAG AAACATCAGAAAACTGAGA AACATCAGAAAACTGAGAA CCAGTCATAAAATTCAAGC TATATTGGTGGCTATCCCC ATATTGGTGGCTATCCCCC TCGGTGTATATATGTGGCT CGGTGTATATATGTGGCTA GGTGTATATATGTGGCTAT TGTTATATTTTGAAAAAAC AGAAAGTTCCTCCCCCTAA GCTCAAAGAGACAAACTCT AGCCTAGGAGAAAGCAACA GACTACACCACCGACGGCC ACTACACCACCGACGGCCC TCCCACTGACGGGCCGCCA AGTCATAAAATTCAAGCTC GTCATAAAATTCAAGCTCC TCATAAAATTCAAGCTCCA TCCACACTTGCCTCAGTGT ATTTTGAAAAATCATCAGA TTTTGAAAAATCATCAGAA TTTGAAAAATCATCAGAAA TAGAAGTTCTAGAAAGTTC AGAAGTTCTAGAAAGTTCT GAAGTTCTAGAAAGTTCTT ATGTGGCTATACCACTGAC TGTGGCTATACCACTGACA TGTGGCTATACCACTGACG GTGGCTATACCACTGACGG AGTCATTAAATTCAAGCTC GTCATTAAATTCAAGCTCC CTAAAGCTTTCCCACTTCC ATCCCACTGACGGGCCGCC CCTCCCCCTAAGGCTTTCA CGAACCCACGGACAGGCCG GATTTTCTAGAAAGTTCCT AGTGTATATATGTGGGTAT GTGTATATATGTGGGTATA TGTATATATGTGGGTATAC AAATATGTGGCTATACCAC NNNTTTCTGAATGTTTCTT NNTTTCTGAATGTTTCTTA TATGTGGCTATACCACTGA TATGTGGCTATACCACTTA CACCACCGACGGCCCGCCA NATTNTNANAAATNNTCAG GAGAATCAAGGATAGAATT GGCTATCCCACTGACAGGC GCTATCCCACTGACAGGCC CTATCCCACTGACAGGCCG TAGAAAGTTCCTCCCCCTA CCTCCCCCTAAAGCTTCAA CTCCCCCTAAAGCTTCAAC TCCCCCTAAAGCTTCAACC GGTGGCTATCCCCCTGAGG CCACGGACGGCCCGCCAGT ATTCAAGCCCCAAGAGACA TTCAAGCCCCAAGAGACAA TCAAGCCCCAAGAGACAAA TATATGAGGCTATACCACT CTAAGAATCAAGGATAGAC TAAGAATCAAGGATAGACT TGGTGGCTATCCCCCTGAG AGTCATTAAATTCAAGCCC GTCATTAAATTCAAGCCCC CCAGGCATTAAATTCAAGC AAGTTCATTCCCCTAAAGC CCCTAAAGCTTTCACACTT CCTAAAGCTTTCACACTTG CTAAAGCTTTCACACTTGC GTAAGAACTGCCCTCCCCC AAACTCTTGAAAAAAAGGC CCCTAAACCTTTCACACTT CCTAAACCTTTCACACTTG CTAAACCTTTCACACTTGC TATCCCCCTGAGGGGCCGC ATCCCCCTGAGGGGCCGCC AAAAGGCAGCCTAGGCGAA AAAGGCAGCCTAGGCGAAA AAGGCAGCCTAGGCGAAAG GCTCCAAGAGACAAACCCT TTTCACTCTTGCCTCAGTG TAAACCTTTCACACTTGCC AAACCTTTCACACTTGCCT TATATGTGGCTATCCCCCT ATATGTGGCTATCCCCCTG TATGTGGCTATCCCCCTGA TTCCCCTAAACCTTTCACA TCCCCTAAACCTTTCACAC CCCCTAAACCTTTCACACT CCACACTTGCCTAGGTGAA AGACTCAAGGGACAAAGCA GACTCAAGGGACAAAGCAG GAGGAGAAAGCAACCGGAT AGGAGAAAGCAACCGGATT TATATTTTGAAAAATCATC ATATTTTGAAAAATCATCA TATTTTGAAAAATCATCAG CCAGTCATTAAATTCAAAC TTCTAGAAAGTTCCTTCCC ACCACTGACGGGCCGCCAG CCTCCCCGTAAAGCTTTCA GAAAGAAACATGATTTTTC ATTNTNANAAATNNTCAGA CCCCCTAAAGCTTTCCCAC CCCCTAAAGCTTTCCCACT CCCTAAAGCTTTCCCACTT AAGAATCAAGGATAGACTT AGAATCAAGGATAGACTTT GTCATTAAATGCAAGCTCC TCATTAAATGCAAGCTCCA TCAGTGTAAATATGTGGCT CAGTGTAAATATGTGGCTA AGTGTAAATATGTGGCTAT CTATACCACTGACGGGCCG TATACCACTGACGGGCCGC GAGACAAGTTTTGGAAAAA GGTGAATATAGGTGGGTAT GTGAATATAGGTGGGTATC TGAATATAGGTGGGTATCC AACTCTTGAAAAAAAGCCA ACTCTTGAAAAAAAGCCAG TGCCTCGGTGTATATATGT GCCTCGGTGTATATATGTG CCTCGGTGTATATATGTGG AATATGTGGCTATACCACT AAAAAGGCAGCCTAGGAGA GAATTTCTAGAAAGTTCCT ACCCACGGACAGGCCGCCA AATTTCTAGAAAGTCCCTC ATTTCTAGAAAGTCCCTCC CAAACTCTTGAAAAAAAGG CAAACTCTTGAAAAAAAGC AGGCAGCCTAGGAGAAAGC ATATGTGACTACACCACCG TATGTGACTACACCACCGA GTTATATTTTGAAAAAACA ATTTCTAGAAAGTTCATTC TTTCTAGAAAGTTCATTCC TTCACACTTGCCTCGGTGT AGCCTAGGAGAAAGAAACA GCCTAGGAGAAAGAAACAT GTGTAAATATGTGGCTATA AGGCAGCCTAGGCGAAAGC GGCAGCCTAGGCGAAAGCA TCATCAGAAAACTAAGAAT TAGGAGATAGCAACATGAT AGGAGATAGCAACATGATT ATATGGGGCTATACCACTG TATGGGGCTATACCACTGA ATGGGGCTATACCACTGAC GACAAAGCAGTAAAATGTG CTAGAAAGTTCATTCCCCT CTAGAAAGTTCCTCCCCCT AGAGACAAACCCTTGAAAA NNNNNNNTTTCTGAATGTT GACGGCCCGCCAGGCATTA GTCCAGTCATTAAATTCAA TTATATTTTGAAAAAACAT GGAGAAAGCAACCGGATTT TGCCTACCCCACTCCCGGG GCCTACCCCACTCCCGGGC TGAAAACTCATCAGAAAAC GAAAACTCATCAGAAAACT AAAACTCATCAGAAAACTG AGTCAATATATGTGACTAC GTCAATATATGTGACTACA TCAATATATGTGACTACAC AAGTTCTAGAAAGTTCTTT AGTTCTAGAAAGTTCTTTG TTGCCTCGGTGTATATATG AAACTCATCAGAAAACTGA TGAAAAAAAGGCAGCCTAG TAACAAATGTGATTTGCCC ATCCCCCTGACAGGCCGCC AAAGGCAGCCTAGGAGAAA AAGGCAGCCTAGGAGAAAG AAATTCAAGCTCAAAGAGA AATTCAAGCTCAAAGAGAC ATTCAAGCTCAAAGAGACA TCCCACCAGTCATTAAATT CCCACCAGTCATTAAATTC CCACCAGTCATTAAATTCA GGAGAAAGAAACATGATTT GAGAAAGAAACATGATTTT TACCACGGACAGGCCGCCA CAACCACCAAGAGACAAAC AAAAAAGCCAGCCTAGGAG AAATTCAAGCCCCAAGAGA AATTCAAGCCCCAAGAGAC CCTCAGTCAATATATGTGA CTCAGTCAATATATGTGAC TCAGTCAATATATGTGACT AGAAAACTGAGAATCAAGG ATTTCTAGAAATTTCCTTC TTTCTAGAAATTTCCTTCC TAAATGCAAGCTCCAAGAG GAAAGCAGCATGATTATTC TTTCTAGAAAGTCCCTCCC CCCTCCCCCTAAGGCTTTC GCTTTCCCACTTCCCTCAG TGGGTATCCCGCTGACAGG CACCAGTCATTAAATTCAA ACCAGTCATTAAATTCAAC TGACGGGCCGCCAGTCCTT GTCCCTCCCCCTAAGGCTT TCCCTCCCCCTAAGGCTTT TCCCCTAAAGCTTCCACAC CCTAAAGCTTTCCCACTTC ATGTGGCTATCCCCCTGAC TGTGGCTATCCCCCTGACA TGTGGCTATCCCCCTGACG GTGGCTATCCCCCTGACAG AATTCAACCACCAAGAGAC AAAGCAGCATGATTATTCA TAAGAACTGCCCTCCCCCT AAGAACTGCCCTCCCCCTA GTGTATATATGGGGCTATA GCTTTCACAGTTGACTCAG CTTTCACAGTTGACTCAGT TTTCACAGTTGACTCAGTG AGCTTTCCCACTTCCCTCA CCTAAAGCTTTCACTCTTG CCCAGTCATTAAATTCAAG CTAAAGCTTTCACTCTTGC TAAGGCTTTCACACTTGCC AAGGCTTTCACACTTGCCT AGGCTTTCACACTTGCCTC GGCCCCCAGTCATTAAATT GCCCCCAGTCATTAAATTC CCCCCAGTCATTAAATTCA ACCACTTACGGGCCGCCAG ATCAAGGATAGAATTTCTA TTCTAGAAATTTCCTTCCC TCTAGAAATTTCCTTCCCC GAACTGCCCTCCCCCTAAA CAGGAGGGGGCGTCCAGTC CTCAGTGTAAATATGTGGC GGCTTTCACACTTGCCTCA GCCACAGTGAAAATTTGTG AAATATGTGCCTATACCAC AATATGTGCCTATACCACG TTCAAGCTCCAAGAGACAA CTAAGGCTTTCACACTTGC TCCCCCTGACAGGCCGCCA CCCCCTGACAGGCCGCCAG TACCACTGACGGGCCGCCA AATCATCAGAAAACTGAGA GAGACAAACTCTTGAAAAA CGACGGCCCGCCAGGCATT ATATGAGGCTATACCACTG CAAGCCCCAAGAGACAAAC CCCCACTCCCGGGCCGCCA ATATGTGGCTATCCCACTG TATGTGGCTATCCCACTGA AAATGCAAGCTCCAAGAGA AGGATAGAAGTTCTAGAAA AAGAGACAAACCCTTGAAA TTGAAAACTCATCAGAAAA CAAGCTCCAAGAAACAAAC TAGGAGAAAGCAACATGAT TCCCCCTGAGGGGCCGCCA CGGACAGGCCGCCAGTCAT AGGCCCCCAGTCATTAAAT CCTACCCCACTCCCGGGCC CCAGTCATTAAATTCAACC ATAGACTCAAGGGACAAAG TAGACTCAAGGGACAAAGC CTCGGTGTATATATGTGGC TCAGTGTATATATGTGGGT CAGTGTATATATGTGGGTA TAGGTGGCTATTCCTTTGA CCCCAGTCATTAAATTCAA GTTTATATATGTGGCTATC TTTATATATGTGGCTATCC AGACAAACTCTTGAAAAAA GACAAACTCTTGAAAAAAA CACACTGGCCTCAGTGTAT ACACTGGCCTCAGTGTATA GCCAGTCATTAAATTCAAG GCCAGTCATTAAATTCAAA TTAAAGCTTCCACACTTGC ATTAAATTCAAGCTCAAAG AAACTCTTGAAAAAAAGCC TAGGTGAATATAGGTGGGT CCGACGGCCCGCCAGGCAT TGGGGCTATACCACTGACA GCCAGTCATTAAATGCAAG CCAGTCATTAAATGCAAGC CAGTCATTAAATGCAAGCT TTAAATTCAAGCTCAAAGA TAAATTCAAGCTCAAAGAG TTGAAAAATCATCAGAAAA CGGAGAAAGCAACATGATT CCCCTAAAGCCTTCACACT CCCTAAAGCCTTCACACTT CCTAAAGCCTTCACACTTG AAAAGGCAGCCTAGGAGAA AAAGCTTTCACAGTTGACT AAGCTTTCACAGTTGACTC AGCTTTCACAGTTGACTCA TATATGTGGCTATCCCACT TATATGTGACTACACCACC TATATGGGGCTATACCACT AGTCATTAAATGCAAGCTC TCACACTTGCCTCGGTGTA TCAAGCTCAAAGAGACAAA CCTCAGTGTATATTGGTGG AAAAAGCCAGCCTAGGAGA CCACTTACGGGCCGCCAGT CAGTCAATATATGTGACTA CCCCCCAGTCATTAAATTC AACCCACGGACAGGCCGCC CTTCCCCTAAACCTTTCAC CCAGTCTTTACTGGTGCTC TTCACACTTGCCTCAGTGT TCACACTTGCCTCAGTGTA GTCCCACCAGTCATTAAAT ATACCACTGACGGGCCGCC AAGCCCCAAGAGACAAACC CCCCCTGAGGGGCCGCCAG CCCCTGAGGGGCCGCCAGT GCAGCCTCGGAGAAAGCAA TGACGGCCCGCCAGTCATT AGCAGTAAAATGTGTAATT TCTAGAAAGTTCCTCCCCC AACCTTTCACACTGGCCTC ACCTTTCACACTGGCCTCA CCTTTCACACTGGCCTCAG CTCAAAGAGACAAACTCTT GCAGTAAAATGTGTAATTT TTCCCCTAAAGCCTTCACA TCCCCTAAAGCCTTCACAC CCCAGGAGGGGGCGTCCAG CCAGGAGGGGGCGTCCAGT GTGCTCTTCCCACTTCCGG CGTCCCACCAGTCATTAAA GACCCCCAGTCATAAAATT AGGTGAATATAGGTGGGTA TGGCTATACCACTGACGGG CTATACCACTGACAGGCCG AGAAAGAAACATGATTTTT GAATCAAGGATAGAAGTTC AATCAAGGATAGAAGTTCT ATTCAAGCTCCAAGAGACA TTCTAGAAAGTTCATTCCC TCTAGAAAGTTCATTCCCC ACTTGCCTCAGTGTATATA GGGTCTCCAGTCATTAAAT GGTCTCCAGTCATTAAATT CGTCCAGTCATTAAATTCA TTATATTTTGAAAACTCAT TATATTTTGAAAACTCATC GATTTCACACTTGTGTCAT ATTTCACACTTGTGTCATT GGCGTCCCACCAGTCATTA GCGTCCCACCAGTCATTAA AAAGCTTCCACACTTGCCT AAGCTTCCACACTTGCCTC AGAACTGCCCTCCCCCTAA ACCGACGGCCCGCCAGGCA ATAGAATTTCTAGAAATTT ATCATCAGAAAACTGAGAA GAACCCACGGACAGGCCGC TCCCTTAAAGCTTCCACAC TATTTTGAAAACTCATCAG TCAGTGTATATATGTGGCT CAGTGTATATATGTGGCTA TTACGGGCCGCCAGTCATT GGATAGAATTTCTAGAAAT GATAGAATTTCTAGAAATT ATCAAGGATAGAAGTTCTA TCAAGGATAGAAGTTCTAG CAAGGATAGAAGTTCTAGA AAAAAGGCAGCCTAGGCGA TCTAGAAAGTTCCTTCCCC ATATTTTGAAAACTCATCA TGAGTGGGGTCTCCAGTCA ACGGACAGGCCGCCAGTCA CCCGCCAGGCATTAAATTC TGTATATATGGGGCTATAC ACCCCCAGTCATAAAATTC TTCAAGCTCAAAGAGACAA CCCCTTGCCTCAGTGTATA GGATAGAATTTCTAGAAAG CATGTAACAAATGTGATTT GGTGCTCTTCCCACTTCCG AAGGATAGAAGTTCTAGAA CAGTCATAAAATTCAAGCT NNNNNNNANATTNTNANAA TGACTACACCACCGACGGC TACGGGCCGCCAGTCATTA CCCAGTCTTTACTGGTGCT CCTAAGGCTTTCACACTTG AGTAATTGTAAGAACTGCC CCCTCCCCGTAAAGCTTTC
- 27. 200bp of a human genome! GGTTTTTCTCATAAAATGA TTTTTCTCATAAAATGATT TTCTCATAAAATGGTTTCT TCTCATAAAATGGTTTCTG TCTCATAAAATGGTTTCTA TTTTCTCATAAAATGGTCT TTTCTCATAAAATGGTCTC TTTGTATGTTTCTTAGCTT TTGTATGTTTCTTAGCTTT GTTTCTAAATGTTTCTTAG ATGTTTCTTAGCTTTCAGT TTAGCTTCCAATGGGCAAT TTAGCTTTCAATGGGGAAT TCCAATGGGCAATAAATAA TTCAATGGGCAGTAAATAA TAAATAACTTTTAGTGAAA AAATAACTTTTAGTGAAAT AATAACTTTTAGTGAAATA CAATCTGAGGAAGTCTTTG AATCTGAGGAAGTCTTTGA ATCTGAGGAAGTCTTTGAG GAAGTCTTTGAGATGGAGG AAGTCTTTGAGATGGAGGG TGAGATGGAGGGAAAGCTT GAGATGGAGGGAAAGCTTT CTATGAGGAGTGCATTAGA GAATAGAATCGCTCCAGGA AATAGAATCGCTCCAGGAA TTATGAGGTGACATTTAAA ATGATTCTTAGGTTTCAAT TGATTCTTAGGTTTCAATG GATTCTTAGGTTTCAATGG TTTTCTCATAAAATGATTT TTTCTCATAAAATGATTTC TAGCTTCCAATGGGCAATA AGCTTCCAATGGGCAATAA GCTTCCAATGGGCAATAAA TTTTTTCTCATAAAATGGT TTTCTAAATGTTTCTTAGC TTCTAAATGTTTCTTAGCT TCTAAATGTTTCTTAGCTT TTTTTCTCATAAAATGGTT TTTTCTCATAAAATGGTTT TTTCAATGGGCAATAAATT ACTTTTCGAGATATTGTTG ATGAAGCGTAGGCTATGCT TGAAGCGTAGGCTATGCTG GAAGCGTAGGCTATGCTGC TTTTTGTATGTTTCTTAGC TTTTGTATGTTTCTTAGCT CAATAAATAACTTTTAGGG AATAAATAACTTTTAGGGA ATAAATAACTTTTAGGGAA AATAACTTTTAGGAAAATA ATAACTTTTAGGAAAATAG TAACTTTTAGGAAAATAGA CTGAGATGAAGAGAAGGCT TGAGATGAAGAGAAGGCTT GAGATGAAGAGAAGGCTTT AGCCATTCTGAGGAAGTTT GCCATTCTGAGGAAGTTTT CCATTCTGAGGAAGTTTTT CATTCTGAGGAAGTTTTTG ATAAAATGGTCTCTGAATG TAAAATGGTCTCTGAATGT AAAATGGTCTCTGAATGTT GCTTTGCTTTCTATGAGGA CTTTGCTTTCTATGAGGAG TTTGCTTTCTATGAGGAGT GTTTCTTAGCTTCAATGGG TCAATGGGCAATAAAAAAC CAATGGGCAATAAAAAACT AATGGGCAATAAAAAACTT AATGGGCAGTAAATAACTT ATGGGCAGTAAATAACTTT AACTTTTAGGGAAATAGAT ACTTTTAGGGAAATAGATG CTTTTAGGGAAATAGATGT GGAAGCATCTGAGATGAAG AGTATTTGAGATGAAGAGA AGCTTTCAATGGGGAATAA GCTTTCAATGGGGAATAAA CTTTCAATGGGGAATAAAT GTATTTGAGATGAAGAGAA TATTTGAGATGAAGAGAAG CCAATCTGAGGAAGCATCT CAATCTGAGGAAGCATCTG AATCTGAGGAAGCATCTGA ATTTGAGATGAAGAGAAGG TAGAAGTGAGCCAATCTGA AGAAGTGAGCCAATCTGAG GAAGTGAGCCAATCTGAGG CTATGCTGCCTTTGATGTG TATGCTGCCTTTGATGTGT ATGCTGCCTTTGATGTGTG AACTTTTAGGGAAATAGAA ACTTTTAGGGAAATAGAAG CTTTTAGGGAAATAGAAGT TTTTTGAGATGAAGCGAAG TTTTGAGATGAAGCGAAGG TTTGAGATGAAGCGAAGGC TGTTTTTCTCATAAAATGG GTTTTTCTCATAAAATGGT TTTTTCTCATAAAATGGTC AGTTTTTCTCATAAAATGG TCATAAAATGATTTCTGAA CATAAAATGATTTCTGAAT ATAAAATGATTTCTGAATG AGTCTTTGAGATGGAGGGA GTCTTTGAGATGGAGGGAA TCTTTGAGATGGAGGGAAA TGAAGCGAAGGCTTTGCTG GTCTATGAGGAGAGCATTA TCTATGAGGAGAGCATTAG CTATGAGGAGAGCATTAGA CCAATCTGTGGAAGCATTT CAATCTGTGGAAGCATTTG AATCTGTGGAAGCATTTGA ATAAAATGGTTTTTGTATG TAAAATGGTTTTTGTATGT AAAATGGTTTTTGTATGTT TTCTCATAAATTGGTTTCT TCTCATAAATTGGTTTCTG CTCATAAATTGGTTTCTGA GTGGGCAATAAATAAATTA TGGGCAATAAATAAATTAT AAGCGTAGGCTATGCTGCC TGATTGCCTTTATGAGGTG GATTGCCTTTATGAGGTGA ATTGCCTTTATGAGGTGAC TGGTTTTTGTATGTTTCTT GGTTTTTGTATGTTTCTTA GTTTTTGTATGTTTCTTAG CTAAATGTTTCTTAGCTTT GGGAAAGCTTTGCTGTCTA GGAAAGCTTTGCTGTCTAT GAGAAGGCTGTGCTGTCTA AGAAGGCTGTGCTGTCTAT GAAGGCTGTGCTGTCTATG TGTATGTTTCTTAGCTTTC GTATGTTTCTTAGCTTTCA TATGTTTCTTAGCTTTCAA TTCTTAGCTTCCAATGGGC TCTTAGCTTCCAATGGGCA CTTAGCTTCCAATGGGCAA AGATGAAGCGAAGGCTTTG GATGAAGCGAAGGCTTTGC ATGAAGCGAAGGCTTTGCT GGAAGCATTTGAGATGAAG GAAGCATTTGAGATGAAGA GAAGCATTTGAGATGAAGC AAGCATTTGAGATGAAGAG AAGCATTTGAGATGAAGCG AATAACTTTTAGGGAAATA ATAACTTTTAGGGAAATAG TAACTTTTAGGGAAATAGA TTTGAGATGAAGAGAAGGC TTTGAGATGAAGAGAAGGG CTTTGAGATGGAGGGAAAG TTTGAGATGGAGGGAAAGC TTGAGATGGAGGGAAAGCT TTTCAATGGGGAATAAATA TTCAATGGGGAATAAATAA TCAATGGGGAATAAATAAC CCAATCTGAGGAAGTATCT CTGAGGAAGTATCTGAGAT TGAGGAAGTATCTGAGATG GAGGAAGTATCTGAGATGA AGGAAGTATCTGAGATGAA GGAAGTATCTGAGATGAAG TGCATTAGAATAGAATCGC GCATTAGAATAGAATCGCT CATTAGAATAGAATCGCTC TTCAATGGGCAATAAATAA TCAATGGGCAATAAATAAC CAATGGGCAATAAATAACT GTGAGCTAATCTGAGTAGG TGAGCTAATCTGAGTAGGT GAGCTAATCTGAGTAGGTA AGATGGAGGGAAAGCTTTG GATGGAGGGAAAGCTTTGC ATGGAGGGAAAGCTTTGCT AGATGAAGAGAAGGCTGTG GATGAAGAGAAGGCTGTGC ATGAAGAGAAGGCTGTGCT AGGGAAAGCTTTGCTGTCT GCTTTGCTGTCTATGAGGA CTTTGCTGTCTATGAGGAG TTTGCTGTCTATGAGGAGA TTTGCTGTCTATGAGGAGT TTGAGATGAAGAGAAGGCT TGAGATGAAGAGAAGGCTG GAGATGAAGAGAAGGCTGT AAGAGAAGGCTTTGCTTTC AGAGAAGGCTTTGCTTTCT GAGAAGGCTTTGCTTTCTA GAAAAGGGCACCTGTGTTG AAAAGGGCACCTGTGTTGA AAAGGGCACCTGTGTTGAT AGCGTAGGCTATGCTGCCT TTGCTTTCTATGAGGAGTG TGCTTTCTATGAGGAGTGC GCTTTCTATGAGGAGTGCA TGAATGATTCTTAGGTTTC GAATGATTCTTAGGTTTCA AATGATTCTTAGGTTTCAA AAGAGAAGGCTTTGCTGTC AGAGAAGGCTTTGCTGTCT GAGAAGGCTTTGCTGTCTA TTTCTGAATGTTTCTTAGC TTCTGAATGTTTCTTAGCT CGCCAATCTGTGGAAGCAT GCCAATCTGTGGAAGCATT TATGAGGAGAGCATTAGAA ATGAGGAGAGCATTAGAAT TGAGGAGAGCATTAGAATA GCTGTCTATGAGGAGTGTA CTGTCTATGAGGAGTGTAT TGTCTATGAGGAGTGTATT AGGAGAGCATTAGAATAGA GGAGAGCATTAGAATAGAA GAGAGCATTAGAATAGAAT TGGAGGGAAAGCTTTGCTG GGAGGGAAAGCTTTGCTGT GAGGGAAAGCTTTGCTGTC CAATGGGCAATAAATTACT AATGGGCAATAAATTACTT ATGGGCAATAAATTACTTT AGAGCATTAGAATAGAATC GAGCATTAGAATAGAATCG AGCATTAGAATAGAATCGC TTAGCTTTCAATGGGCAAT TAGCTTTCAATGGGCAATA AGCTTTCAATGGGCAATAA GTGCGCCAATCTGTGGAAG TGCGCCAATCTGTGGAAGC GCGCCAATCTGTGGAAGCA GAGGAGAGCATTAGAATAG TTTTAGGGAAATAGAAGTG GCAATAAATTACTTTTCGA CAATAAATTACTTTTCGAG AATAAATTACTTTTCGAGA GAGCCAATCTGAGGAAGTC AGCCAATCTGAGGAAGTCT GCCAATCTGAGGAAGTCTT AGATGAAGAGAAGGCTTTG GATGAAGAGAAGGCTTTGC ATAGAATCGCTCCAGGAAA TAGAATCGCTCCAGGAAAA AGAATCGCTCCAGGAAAAG GGGCAGTAAATAACTTTTA GGCAGTAAATAACTTTTAG GCAGTAAATAACTTTTAGG AATCTGAGGAAGCATTTGA ATCTGAGGAAGCATTTGAG TCTGAGGAAGCATTTGAGA GGTTTTTCTCATAAAATGG ATGGGCAATAAATAGCTTT TGGGCAATAAATAGCTTTT AAGCATCTGAGATGAAGAG AGCATCTGAGATGAAGAGA GCATCTGAGATGAAGAGAA TTCTTAGCTTTCAATGGGG TCTTAGCTTTCAATGGGGA CTTAGCTTTCAATGGGGAA AGTGCATTAGAATAGAATT GTGCATTAGAATAGAATTG TGCATTAGAATAGAATTGC AAAGGTCACCTGTGTTGAT AAGGTCACCTGTGTTGATT AGGTCACCTGTGTTGATTG ATCGCTCCAGGAAAAGGGC TCGCTCCAGGAAAAGGGCA CGCTCCAGGAAAAGGGCAC TAGATGTGAGCTAATCTGA AGATGTGAGCTAATCTGAG GATGTGAGCTAATCTGAGT CCAGGAAAAGGGCACCTGT CAGGAAAAGGGCACCTGTG AGGAAAAGGGCACCTGTGT TAAATAACTTTTAGGAAAA AAATAACTTTTAGGAAAAT GGAAAAGGTCACCTGTGTT GAAAAGGTCACCTGTGTTG AAAAGGTCACCTGTGTTGA TCATAAATTGGTTTCTGAA CATAAATTGGTTTCTGAAT ATAAATTGGTTTCTGAATG GTATTAGAATAGAATCGCT TATTAGAATAGAATCGCTC ATTAGAATAGAATCGCTCC GAGATGAAGAGAAGGGTTT AGATGAAGAGAAGGGTTTG GATGAAGAGAAGGGTTTGC ATCTGAGGAAGTATTTGAG TCTGAGGAAGTATTTGAGA CTGAGGAAGTATTTGAGAT GCTGTGCTGTCTATGAGGA CTGTGCTGTCTATGAGGAG TGTGCTGTCTATGAGGAGT AGAATTGCTCCAGGAAAAG GAATTGCTCCAGGAAAAGG AATTGCTCCAGGAAAAGGT AAGTTTTTGAGATGAAGCG AGTTTTTGAGATGAAGCGA GTTTTTGAGATGAAGCGAA AATAGAAGTGAGCCAATCT ATAGAAGTGAGCCAATCTG CTCATAAAATGGTTTCTGA TCATAAAATGGTTTCTGAA CATAAAATGGTTTCTGAAT AATAGAATTGCTCCAGGAA ATAGAATTGCTCCAGGAAA TAGAATTGCTCCAGGAAAA CCAATGGGCAATAAATAAC AATGGGCAATAAATAACTT TAGCTTTCAATGGGGAATA TTGCTGTCTATGAGGAGAG TGCTGTCTATGAGGAGAGC TTTCTCATAAAATGGTTTC TTTCTCATAAAATGGTTTT ATTGCTCCAGGAAAAGGTC TTGCTCCAGGAAAAGGTCA TGCTCCAGGAAAAGGTCAC CTGAATGTTTCTTAGCTTT TGAATGTTTCTTAGCTTTC GAATGTTTCTTAGCTTTCA GCTTTCAATGGGCAATAAA CTTTCAATGGGCAATAAAT TCTCATAAAATGGTCTCTG CTCATAAAATGGTCTCTGA TCATAAAATGGTCTCTGAA GTTTCTGAATGATTCTTAG TTTCTGAATGATTCTTAGG TTCTGAATGATTCTTAGGT CAGGAAAAGGTAACGTGAG AGGAAAAGGTAACGTGAGG GGAAAAGGTAACGTGAGGT CTTCAATGGGCAATAAAAA TTCAATGGGCAATAAAAAA TGTTTCTTAGCTTTCAATG GTTTCTTAGCTTTCAATGG TTTCTTAGCTTTCAATGGG GGGCAATAAATTACTTTTC GGCAATAAATTACTTTTCG CTTGCAATGGGCAATAAAT TTGCAATGGGCAATAAATA TGCAATGGGCAATAAATAA CAATGGGGAATAAATAACT AATGGGGAATAAATAACTT GCGAAGGCTTTGCTGTCTA CGAAGGCTTTGCTGTCTAT GAAGGCTTTGCTGTCTATG TTTAGGGAAATAGATGTGA TTAGGGAAATAGATGTGAG TAGGGAAATAGATGTGAGC GAATGTTTCTTAGCTTCCA AATGTTTCTTAGCTTCCAA ATGTTTCTTAGCTTCCAAT TCTGAATGATTCTTAGGTT TTCAGTGGGCAATAAATAA TCAGTGGGCAATAAATAAA CAGTGGGCAATAAATAAAT GAAGAGAAGGCTTTGCTTT GCTGTCTATGAGGAGTGCA CTGTCTATGAGGAGTGCAT TGTCTATGAGGAGTGCATT AACTTTTAGGAAAATAGAT ACTTTTAGGAAAATAGATG AAGGCTTTGCTGTCTATGA TAGCTTTCAATGGGCAGTA AGCTTTCAATGGGCAGTAA GCTTTCAATGGGCAGTAAA AGAGAAGGCTGTGCTGTCT CCTGTGTTGATTGCCTTTA CTGTGTTGATTGCCTTTAT TGTGTTGATTGCCTTTATG TGAGGAAGTATTTGAGATG GAGGAAGTATTTGAGATGA GGAATAAATAACTTTTACG GAATAAATAACTTTTACGG AATAAATAACTTTTACGGA AAACTTTTAGGGAAATAGA TAGAATAGAATTGCTCCAG AGAATAGAATTGCTCCAGG GAATAGAATTGCTCCAGGA ATGGTTTCTGAATGTTTCT TGGTTTCTGAATGTTTCTT GGTTTCTGAATGTTTCTTA TTTTCTCATAAATTGGTTT TTTCTCATAAATTGGTTTC TATGAGGAGTGCATTAGAA ATGAGGAGTGCATTAGAAT TGAGGAGTGCATTAGAATA TTCTCATAAAATGATTTCT CCAATCTGAGGAAGTCTTT AGCTAATCTGAGTAGGTAT CAATCTGAGGAAGTATCTG AATCTGAGGAAGTATCTGA ATCTGAGGAAGTATCTGAG TGTGAGCCATTCTGAGGAA GTGAGCCATTCTGAGGAAG TGAGCCATTCTGAGGAAGT AAAACTTTTAGGGAAATAG ATGAGGAGTGTATTAGAAT TGAGGAGTGTATTAGAATA GAGGAGTGTATTAGAATAG GGTTTTTCTCATAAATTGG GTTTTTCTCATAAATTGGT AAATGTTTCTTAGCTTTCA AATGTTTCTTAGCTTTCAA ATGTTTCTTAGCTTTCAAT TTGAGATGAAGCGTAGGCT TGAGATGAAGCGTAGGCTA GAGATGAAGCGTAGGCTAT TATGAGGAGTGTATTAGAA TGGGGAATAAATAACTTTT GGGGAATAAATAACTTTTA GGGAATAAATAACTTTTAC GGTTTCTGAATGATTCTTA CGCTCCAGGAAAAGGTCAC GCTCCAGGAAAAGGTCACC CTCCAGGAAAAGGTCACCT GTCACCTGTGTTGATTGCC TCACCTGTGTTGATTGCCT CACCTGTGTTGATTGCCTT GTGTTGATTGCCTTTATGA AGAAGGCTTTGCTTTCTAT GAAGGCTTTGCTTTCTATG AAGGCTTTGCTTTCTATGA GAGATGAAGCGAAGGCTTT TCTGAGGAAGTATCTGAGA TGAGGAAGCATCTGAGATG GAGGAAGCATCTGAGATGA AGGAAGCATCTGAGATGAA GCTCCAGGAAAAGGGCACC TCGCTCCAGGAAAAGGTCA TCAATGGGCAGTAAATAAC CAATGGGCAGTAAATAACT ATTCTTAGGTTTCAATGGG TTCTTAGGTTTCAATGGGC TCTTAGGTTTCAATGGGCA CTGTCTATGAGGAGAGCAT TGTCTATGAGGAGAGCATT AGCCAATCTGAGGAAGCAT GCCAATCTGAGGAAGCATC GCCAATCTGAGGAAGCATT CCAATCTGAGGAAGCATTT TTTCTATGAGGAGTGCATT TTCTATGAGGAGTGCATTA TCTATGAGGAGTGCATTAG AAGGCTGTGCTGTCTATGA GAAGCATCTGAGATGAAGA ATGAAGAGAAGGGTTTGCT TGAAGAGAAGGGTTTGCTG GAAATAGATGTGAGCCAAT AAATAGATGTGAGCCAATC AATAGATGTGAGCCAATCT TTAGAATAGAATCGCTCCA TTCTCATAAAATGGTTTTT TCTCATAAAATGGTTTTTG CTCATAAAATGGTTTTTGT CTCCAGGAAAAGGTAACGT TCCAGGAAAAGGTAACGTG CCAGGAAAAGGTAACGTGA TTGATTGCCTTTATGAGGT GAAGTATCTGAGATGAAGA AGGAAAAGGTCACCTGTGT ACCTGTGTTGATTGCCTTT AGGAGTGTATTAGAATAGA GGAGTGTATTAGAATAGAA GAGTGTATTAGAATAGAAT TAAATGTTTCTTAGCTTTC TCTTAGCTTCAATGGGCAA CTTAGCTTCAATGGGCAAT TTAGCTTCAATGGGCAATA AAGGGCACCTGTGTTGATT TCTGTGGAAGCATTTGAGA CTGTGGAAGCATTTGAGAT TGTGGAAGCATTTGAGATG TTGGTTTCTGAATGATTCT TGGTTTCTGAATGATTCTT AATGGTTTCTAAATGTTTC ATGGTTTCTAAATGTTTCT TGGTTTCTAAATGTTTCTT TTGAGATGAAGCGAAGGCT TGAGATGAAGCGAAGGCTT ATCTGAGGAAGCATCTGAG TCTGAGGAAGCATCTGAGA CTCCAGGAAAAGGGCACCT TAACTTTTACGGAAATAGA AACTTTTACGGAAATAGAT ACTTTTACGGAAATAGATG AGCATTTGAGATGAAGAGA GCATTTGAGATGAAGAGAA TAGGTTTCAATGGGCATTA AGGTTTCAATGGGCATTAA GGTTTCAATGGGCATTAAA ATAAATTACTTTTCGAGAT GGAAAATAGATGTGAGCCA GAAAATAGATGTGAGCCAA AAAATAGATGTGAGCCAAT AGGCTATGCTGCCTTTGAT GGCTATGCTGCCTTTGATG GCTATGCTGCCTTTGATGT AGGCTTTGCTGTCTATGAG GGCTTTGCTGTCTATGAGG TTTCGAGATATTGTTGTGC TTCGAGATATTGTTGTGCG TCGAGATATTGTTGTGCGC AGAAGGCTTTGCTGTCTAT CTGAATGTTTCTTAGCTTC TGAATGTTTCTTAGCTTCC GTAGGCTATGCTGCCTTTG TAGGCTATGCTGCCTTTGA GCCTTTATGAGGTGACATT CCTTTATGAGGTGACATTT CTTTATGAGGTGACATTTA TTTCAATGGGCAATAAATA TTTTTCTCATAAATTGGTT TTAGCTTTCAATGGGCAGT TCAATGGGCAATAAATAGC CAATGGGCAATAAATAGCT AATGGGCAATAAATAGCTT AAATGGTTTTTGTATGTTT AATGTTTCTTAGCTTTCAG AATCGCTCCAGGAAAAGGT ATCGCTCCAGGAAAAGGTA ATCGCTCCAGGAAAAGGTC TCGCTCCAGGAAAAGGTAA TCGCTCCAGGAAAAGGTCC TAAAAAACTTTTAGGGAAA AAAAAACTTTTAGGGAAAT AAAAACTTTTAGGGAAATA GAATCGCTCCAGGAAAAGG ATTGTTGTGCGCCAATCTG TTGTTGTGCGCCAATCTGT TGTTGTGCGCCAATCTGTG CAGGAAAAGGTCACCTGTG AGGGCACCTGTGTTGATTG GGGCACCTGTGTTGATTGC GGCACCTGTGTTGATTGCC TTTCTTAGCTTCAATGGGC TTCTTAGCTTCAATGGGCA CTCATAAAATGGTTTCTAA TCATAAAATGGTTTCTAAA CATAAAATGGTTTCTAAAT ATGTGAGCTAATCTGAGTA GTCTATGAGGAGTGCATTA TCTCATAAAATGATTTCTG CTCATAAAATGATTTCTGA CATTTGAGATGAAGAGAAG GTTGTGCGCCAATCTGTGG TTGTGCGCCAATCTGTGGA ATGAAGAGAAGGCTTTGCT TAAAATGGTTTCTAAATGT AAAATGGTTTCTAAATGTT AAATGGTTTCTAAATGTTT TTCTTAGCTTTCAGTGGGC TCTTAGCTTTCAGTGGGCA CTTAGCTTTCAGTGGGCAA ATAAATAACTTTTACGGAA TAAATAACTTTTACGGAAA CTGAGGAAGTCTTTGAGAT TGAGGAAGTCTTTGAGATG GAGGAAGTCTTTGAGATGG CTTTCTATGAGGAGTGCAT AATCGCTCCAGGAAAAGGG GTGGAAGCATTTGAGATGA TGGAAGCATTTGAGATGAA TTGAGATGAAGAGAAGGGT TGAGATGAAGAGAAGGGTT GCATTTGAGATGAAGCGTA CATTTGAGATGAAGCGTAG ATTTGAGATGAAGCGTAGG AGGCTTTGCTTTCTATGAG GGCTTTGCTTTCTATGAGG TAAATAACTTTTAGGGAAA AAATAACTTTTAGGGAAAT TCAATGGGCAATAAATTAC TAGGGAAATAGAAGTGAGC AGGGAAATAGAAGTGAGCC GGGAAATAGAAGTGAGCCA CTGAGGAAGCATCTGAGAT ATAAAATGGTTTCTAAATG AATAACTTTTACGGAAATA ATAACTTTTACGGAAATAG TCTGAGTAGGTATTTGAGA CTGAGTAGGTATTTGAGAT TGAGTAGGTATTTGAGATG TCCAGGAAAAGGTCACCTG TCATAAAATGGTTTTTGTA TGCTGCCTTTGATGTGTGC GCTGCCTTTGATGTGTGCT TGTTTCTTAGCTTCCAATG GTTTCTTAGCTTCCAATGG GCAATGGGCAATAAATAAC AATTACTTTTCGAGATATT ATTACTTTTCGAGATATTG TTACTTTTCGAGATATTGT ATGGGCAATAAAAAACTTT TGGGCAATAAAAAACTTTT CAATCTGAGGAAGCATTTG CAATAAATAACTTTTAGGA AATAAATAACTTTTAGGAA ATAAATAACTTTTAGGAAA AAATTGGTTTCTGAATGAT AATTGGTTTCTGAATGATT ATTGGTTTCTGAATGATTC TTTATGAGGTGACATTTAA AGGGAAATAGATGTGAGCC AGGGAAATAGATGTGAGCT GGGAAATAGATGTGAGCCA GGGAAATAGATGTGAGCTA GTTTTTCTCATAAAATGAT CTTCCAATGGGCAATAAAT TTCCAATGGGCAATAAATA AGGAGTGCATTAGAATAGA GGAGTGCATTAGAATAGAA GAGTGCATTAGAATAGAAT CCAATCTGAGGAAGTATTT CAATCTGAGGAAGTATTTG AATCTGAGGAAGTATTTGA CAGTAAATAACTTTTAGGG AGTAAATAACTTTTAGGGA TTCTGAGGAAGTTTTTGAG TCTGAGGAAGTTTTTGAGA CTGAGGAAGTTTTTGAGAT TTTTAGGGAAATAGATGTG TTCAATGGGCAATAAATAG AATAAATAACTTTTAGTGA ATAAATAACTTTTAGTGAA TTGCCTTTATGAGGTGACA TGCCTTTATGAGGTGACAT AGTGGGCAATAAATAAATT AATGTTTCTTAGCTTCAAT ATGTTTCTTAGCTTCAATG TGTTTCTTAGCTTCAATGG GTAAATAACTTTTAGGGAA ATTCTGAGGAAGTTTTTGA TGGGCAGTAAATAACTTTT CGCTCCAGGAAAAGGTAAC GCTCCAGGAAAAGGTAACG AGGCTGTGCTGTCTATGAG GGCTGTGCTGTCTATGAGG GCGTAGGCTATGCTGCCTT CGTAGGCTATGCTGCCTTT CCAGGAAAAGGTCACCTGT CTTAGGTTTCAATGGGCAT TTAGGTTTCAATGGGCATT TTCAATGGGCAATAAATTA TGGGCAATAAATTACTTTT TGAGCCAATCTGAGGAAGC GAGCCAATCTGAGGAAGCA ATGGGGAATAAATAACTTT TGTGAGCTAATCTGAGTAG AGGTATTTGAGATGAAGAG GGTATTTGAGATGAAGAGA GCTGTCTATGAGGAGAGCA GCATTAGAATAGAATTGCT CATTAGAATAGAATTGCTC ATTAGAATAGAATTGCTCC AGTGAGCCAATCTGAGGAA GTGAGCCAATCTGAGGAAG TGAGCCAATCTGAGGAAGT TCTATGAGGAGTGTATTAG CTATGAGGAGTGTATTAGA GGAAATAGAAGTGAGCCAA GTTTCTGAATGTTTCTTAG CATCTGAGATGAAGAGAAG TAAATTACTTTTCGAGATA AAATTACTTTTCGAGATAT GGAAAAGGGCACCTGTGTT AAGTGAGCCAATCTGAGGA TTCTTAGCTTTCAATGGGC TCTTAGCTTTCAATGGGCA CTTAGCTTTCAATGGGCAA AGCTTTCAGTGGGCAATAA GCTTTCAGTGGGCAATAAA CTTTCAGTGGGCAATAAAT TGTATTAGAATAGAATCGC AAATAACTTTTACGGAAAT AGATGAAGCGTAGGCTATG GATGAAGCGTAGGCTATGC GAAATAGAAGTGAGCCAAT AAATAGAAGTGAGCCAATC TAAATTGGTTTCTGAATGA GAGTAGGTATTTGAGATGA AGTAGGTATTTGAGATGAA TTTCTTAGCTTCCAATGGG TGAAGAGAAGGCTGTGCTG TCTGAATGTTTCTTAGCTT TTAGCTTTCAGTGGGCAAT TAGCTTTCAGTGGGCAATA TGTGAGCCAATCTGAGGAA TGAGGAAGTTTTTGAGATG GAGGAAGTTTTTGAGATGA AATGGTTTTTGTATGTTTC TTTAGGAAAATAGATGTGA TTAGGAAAATAGATGTGAG TAGGAAAATAGATGTGAGC GTTTTTTCTCATAAAATGG TAGCTTCAATGGGCAATAA AGCTTCAATGGGCAATAAA GCTTCAATGGGCAATAAAA AGGAAGTCTTTGAGATGGA GGAAGTCTTTGAGATGGAG GTGTATTAGAATAGAATCG GAAGTTTTTGAGATGAAGC GTCTATGAGGAGTGTATTA AGCATTTGAGATGAAGCGT TAATCTGAGTAGGTATTTG AATCTGAGTAGGTATTTGA ATCTGAGTAGGTATTTGAG AGATGTGAGCCAATCTGAG GATGTGAGCCAATCTGAGG ATGTGAGCCAATCTGAGGA TGTGCGCCAATCTGTGGAA ATCTGAGATGAAGAGAAGG TCTGAGATGAAGAGAAGGC GAAGAGAAGGGTTTGCTGT ATGGGCAATAAATAACTTT GGAAGTATTTGAGATGAAG GAAGTATTTGAGATGAAGA AAGTATTTGAGATGAAGAG GAGCCATTCTGAGGAAGTT GCCAATCTGAGGAAGTATT GCTAATCTGAGTAGGTATT TTTCAGTGGGCAATAAATA AGGAAGTATTTGAGATGAA TAGGTATTTGAGATGAAGA GGGCAATAAATAACTTTTA GGCAATAAATAACTTTTAG GCAATAAATAACTTTTAGT GCAATAAATAACTTTTAGG CTTTCAATGGGCAGTAAAT GGAAATAGATGTGAGCCAA TTTTAGGAAAATAGATGTG GTTGATTGCCTTTATGAGG AAGAGAAGGGTTTGCTGTC AGAGAAGGGTTTGCTGTCT CGAGATATTGTTGTGCGCC GAGATATTGTTGTGCGCCA AGATATTGTTGTGCGCCAA GAGGAAGCATTTGAGATGA AGGAAGCATTTGAGATGAA TTGCTGTCTATGAGGAGTG TGCTGTCTATGAGGAGTGC TGCTGTCTATGAGGAGTGT TCCAGGAAAAGGGCACCTG TTTCTTAGCTTTCAGTGGG ATCTGTGGAAGCATTTGAG GGAAATAGATGTGAGCTAA GAAATAGATGTGAGCTAAT ATAAAATGGTTTCTGAATG GAAGCGAAGGCTTTGCTGT TGGGCAATAAATAACTTTT AAATGGTTTCTGAATGTTT AATGGTTTCTGAATGTTTC AGGAAGTTTTTGAGATGAA GGAAGTTTTTGAGATGAAG TTCTCATAAAATGGTCTCT TTTGAGATGAAGCGTAGGC AGTGCATTAGAATAGAATC TTTAGGGAAATAGAAGTGA TTAGGGAAATAGAAGTGAG AGTGTATTAGAATAGAATC GGCAATAAAAAACTTTTAG GCAATAAAAAACTTTTAGG CAATAAAAAACTTTTAGGG ATAGATGTGAGCTAATCTG CTGAATGATTCTTAGGTTT GTTTCTTAGCTTTCAGTGG CATAAAATGGTCTCTGAAT ATAAAAAACTTTTAGGGAA TACTTTTCGAGATATTGTT TGTTGATTGCCTTTATGAG CATAAAATGGTTTTTGTAT AAGAGAAGGCTGTGCTGTC GGGCAATAAAAAACTTTTA AATAGATGTGAGCTAATCT GTAGGTATTTGAGATGAAG AGGAAAATAGATGTGAGCC CTGAGGAAGCATTTGAGAT TGAGGAAGCATTTGAGATG AGCGAAGGCTTTGCTGTCT CTAATCTGAGTAGGTATTT CTTTTAGGAAAATAGATGT TTAGAATAGAATTGCTCCA GTGCATTAGAATAGAATCG ATATTGTTGTGCGCCAATC TATTGTTGTGCGCCAATCT TCTGAGGAAGTCTTTGAGA GAAGAGAAGGCTGTGCTGT AGCCAATCTGAGGAAGTAT GCCAATCTGAGGAAGTATC GATATTGTTGTGCGCCAAT TAAAATGGTTTCTGAATGT AAAATGGTTTCTGAATGTT CAATAAATAACTTTTAGTG GGTTTCTAAATGTTTCTTA TAGAATAGAATCGCTCCAG ATGGTTTTTGTATGTTTCT GAGGAGTGCATTAGAATAG AATAAAAAACTTTTAGGGA TTTTCGAGATATTGTTGTG TGTTTCTTAGCTTTCAGTG GAAGAGAAGGCTTTGCTGT TTTCAATGGGCAGTAAATA GGTCACCTGTGTTGATTGC ATAGATGTGAGCCAATCTG TAGATGTGAGCCAATCTGA CTGCCTTTGATGTGTGCTT GAGCCAATCTGAGGAAGTA AAGCGAAGGCTTTGCTGTC AAATAGATGTGAGCTAATC GCACCTGTGTTGATTGCCT GTTTCAATGGGCATTAAAT AGAATAGAATCGCTCCAGG CTTTTCGAGATATTGTTGT TGAAGAGAAGGCTTTGCTG TGAAGAGAAGGCTTTGCTT TGCCTTTGATGTGTGCTTT There are over 3000 20-mers,! and over 30 valid paths!
- 28. Help‽ What Can We Do? • For some errors, we can inspect the de Brujin graph directly, and eliminate edges from the graph • More generally, we can look at the distribution of k-mers, and try to make corrections to the reads
- 29. Trimming Spurs • Since errors are at the ends of reads, we see spurious branches off of the graph • Use heuristics to determine whether we can remove these nodes • E.g., if these nodes are only present in 1 read, probably OK
- 30. The k-mer Spectrum • If we look at the frequencies of k-mers, we see something interesting…
- 31. What Is This Spike?
- 32. Those Are Our Errors! • Errors create low-frequency substrings • We can identify errors with a mixture model: • Mixture of poissons • Distribution with lowest mean —> errors • From here, we can remove those “erroneous” strings, and pick likely replacements
- 33. How Do We Define Likely? • Can use edit distance of replacement as a heuristic • Can define a probabilistic measure for the quality of a replacement:
- 34. Dealing With Repeats • A cycle in a de Brujin graph is caused by repeated sequence • In real genomes, there is a lot of repetition: • Structural variation —> duplicated sequences • Transposons/Mobile Elements • Centromeres and Telomeres
- 35. Increased k-mer Length ACA CAC ACT GCA TGC CTG ACACTGCACT ACACT CACTG ACTGC GCACT TGCAC CTGCA • If we have a sequence which is less than b bases long, we can resolve the repeat by using k-mers with k > b
- 36. Scaffolding It was the best of times, it was the worst of times… the best of best of times was the worst It was the worst of times times, it was • Current sequencing technology gives us paired reads, with approximately known distance between reads
- 37. Scaffolding • We can use this to estimate repeat sizes: • Or, to estimate the size of gaps: smaller! bigger!
- 38. How About Large Repeats? Twitter, @infoecho, 9/12/2014
- 39. Long Reads To The Rescue!
- 40. Opportunities • New read technologies are available • Provide much longer reads (250bp vs. >10kbp) • Different error model… (15% INDEL errors, vs. 2% SNP errors) • Generally, lower sequence specific bias • But, need to improve OLC assembler performance! Left: PacBio homepage, Right: Wired, http://www.wired.com/2012/03/oxford-nanopore-sequencing-usb/
- 41. Can we turn an expensive, serial problem into a cheap, parallel problem?
- 42. Fast Overlapping with MinHashing • Wonderful realization by Berlin et al1: overlapping is similar to document similarity problem • Use MinHashing to approximate similarity: 1: Berlin et al, bioRxiv 2014 Per document/read, compute signature:! ! 1. Cut into shingles 2. Apply random hashes to shingles 3. Take min over all random hashes Hash into buckets:! ! Signatures of length l can be hashed into b buckets, so we expect to compare all elements with similarity ≥ (1/b)^(b/l) Compare:! ! For two documents with signatures of length l, Jaccard similarity is estimated by (# equal hashes) / l ! Can reduce complexity from O(n2) to O(nb)!
- 43. MapReduce • Intuition: if we have a data parallel algorithm, we can run the algorithm across many computers • Many popular systems: • MapReduce at Google • Hadoop • (from Berkeley!) • Provide special programming models for graphs…
- 44. MinHash On MR Per document/read, compute signature:! ! 1. Cut into shingles 2. Apply random hashes to shingles 3. Take min over all random hashes Hash into buckets:! ! Signatures of length l can be hashed into b buckets, so we expect to compare all elements with similarity ≥ (1/b)^(b/l) Compare:! ! For two documents with signatures of length l, Jaccard similarity is estimated by (# equal hashes) / l ! map groupBy map + filter
- 45. Transitive Reduction • We can find a consensus between clique members • Or, we can reduce down: • Can be implemented efficiently using graph-optimized MapReduce libraries!