Study the Evolution of the Avian Influenza Virus
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1 Designing an Algorithm to Study the Evolution of the Avian Influenza Virus Arti Khana Mentor: Takis Benos Rachel Brower-Sinning Department of Computational Biology University of Pittsburgh
2 Overview Introduction Background Goals Methods Results Acknowledgements
3 Introduction Study evolutionary aspects of flu viruses Develop genetic algorithm (GA) given Starting flu genome sequence Set of amino acid substitutions Mutation rate Fitness function
4 Background Avian influenza A (H5N1) Ten main proteins shown
5 Background Avian virus can mutate to fully adapt to humans Types of mutations Point Mutation Deletion Insertion Inversion
6 Background Position-Specific Scoring Matrix Assign probabilities Include pseudo counts Log of probabilities
7 Goals Develop an algorithm that given an initial human and avian DNA sequence it will generate N new sequences based on some parameters. Rate of mutations Number of successive mutations Selection of mutated sequences Number of generations Assign probabilities for each sequence and use a position-specific scoring matrix to align and score sequences. Selecting top X sequences (e.g., X=100) and repeat K number of times. If two sequences are given in the input, then evolve both and every T time recombine their segments randomly.
8 Methods Flow Chart of Algorithm Implemented Avian Sequence Human Sequence Generate Mutate Translate Fitness Function Select Score
9 Methods Read in human nucleotide sequence Translate sequence Read in avian nucleotide sequence For a given number of generations Mutate avian sequences Translate avian sequences Read translated sequences into fitness function Select sequences Print best sequence and score
10 Results Mutated sequences >gi gb AB _/Avian/5(NP)/... ATGGCGCTTCAAGGCACCAAACGATCTTATGAGCAGATGGAAACTGGTGGGGAACGCCAGA ATGCTACTGAGATCAGAGCATCTGTTGGGAGAATGGTTGGTGGAATCGGAAGATTCTACATA CAGATGTGCACTGAACTCAAACTCAGCGACTACGAAGGCAGGCTGATCCAAAACAGCATAAC AATAGAGAGAATGGTCCTCTCCGCATTTGATGAAAGGAGGAACAGATACCTGGAAGAAAGTC CCAGTGCGGGGAAAGATCCGAAGAAAACTGGAGGTCCAATCTACAAAAGAAGGGAAGGAAA GTGGGTGAGAGAGCTGATTTTGTATGACAAGGAGGAGATCAGGAGAATTTGGCGTCAAGCG AACAATGGAGAAGACGCAACTGCTGGCCTCACCCATCTGATGATCTGGCATTCCAATCTGAA TGATGCCACATATCAAAGAACAAGAGCTCTAGTGCGTACTGGGATGGACCCCAGAATGTGTT CTCTGATGCAAGGATCAACTCTCCCGAGAAGATCAGGAGCTGCTGGTGCAGCAGTAAAGGG AATTGGGACAATGGTGATGGAACTAATTCGGATGATAAAGCGGGGAATCAATAACCGGAATT TCTGG >gi gb AB _/Avian/5(NP)... ATGGCGCTTCAAGGCACCAAACGATCTTATGAGCAGATGGAAACTGGTGGGGAACGCCAGA ATGCTACTGAGATCAGAGCATCTGTTGGGAGAATGGTTGGTGGAATCGGAAGATTCTACATA CAGATGTGCACTGAACTCAAACTCAGCGACTACGAAGGCAGGCTGATCCAAAACAGCATAAC AATAGAGAGAATGGTCCTCTCCGCATTTGATGAAAGGAGGAACAGATACCTGGAAGAAAGTC CCAGTGCGGGGAAAGATCCGAAGAAAACTGGAGGTCCAATCTACAAAAGAAGGGAAGGAAA GTGGGTGAGAGAGCTGATTTTGTATGACAAGGAGGAGATCAGGAGAATTTGGCGTCAAGCG AACAATGGAGAAGACGCAACTGCTGGCCTCACCCATCTGATGATCTGGCATTCCAATCTGAA TGATGCCACATATGAAAGAACAAGAGCTCTAGTGCGTACTGGGATGGACCCCAGAATGTGTT CTCTGATGCAAGGATCAACTCTCCCGAGAAGATCAGGAGCTGCTGGTGCAGCAGTAAAGGG AATTGGGACAATGGTGATGGAACTAATTCGGATGATAAAGCGGGGAATCAATAACCGGAATT TCTGG
11 Results Scored Sequences max possible score >gi gb AF _/Avian/5(NP)/... MALQGTKRSYEQMETGGERQNATEIRASVGRMVGGIGRFYIQMCTELKLSDYEGRLIQNSITIERMVLSAFDERRNRYLEENPSAGKDPKK TGGPIYKRREGKWVRELILYDKEEIRRIWRQANNGEDATAGLTHLMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAG AAVKGIGTMVMELIRMIKRGINDRNFWRGDNGRRTRIAYERMCNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFLARSALILRGSVAH KSCLPACVYGLAVASGYDFEREGYSLVGIDPFRLLQNSQVFSLIRSNENPAHKSQLVWMACHSAAFEDLRVSSFIRGTRVIPRGQLSTRGV QIASNENMETIDSSTLELRSRYWAIRTRSGGNTNQHRASAGQISVQPTFSVQRSLPFERATIMAAFTGNTEGRTSDMRTEIIRMMENAKPE DVSFQGRGVFELSDEKATNPIVPSFDMSNEG >gi gb AF _/Avian/5(NP)/... MALQGTKRSYEQMETGGERQNATEIRASVGRMVGGIGRFYIQMCTELKLSDYEGRLIQNSITIERMVLSAFDERRNRYLEENPSAGKDPKK TGGPIYKRREGKWVRELILYDKEEIRRIWRQANNGEDATAGLTHLMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAG AAIKGIGTMVMELIRMIKRGINDRNFWRGDNGRRTRIAYERMCNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFLARSALILRGSVAH KSCLPACVYGLAVASGYDFDREGYSLVGIDPFRLLQNSQVFNLIRSNENPAHKSQLVWMACHSAAFEDLRVSSFIRGTRVIPRGQLSTRGV QIASNENMETIDSSTLELRSRYWAIRTRSGGNTNQHRASAGQISVQPTFSVQRSLPFERATIMAAFTGNTEGRTSDMRTEIIRMMENAKPE DVSFQGRGVFELSDEKATNPIVPSFDMSNE >gi gb AM _/Avian/5(NP... MASQGTKRSYEQMETGGERQNATEIRASVGRMISGIGRFYIQMCTELKLSDYEGRLIQNSITIERMVLSAFDERRNRYLEEHPSAGKDPKK TGGPIYRRRDGKWVRELILYDKEEIRRIWRQANNGEGATAGLTHLMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAG AAVKGVGTMVMELIRMIKRGINDRNFWRGENGRRTRIAYERMCNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFLARSALILRGSVA HKSCLPACVYGLAVAGGYDFEREGYSLVGIDPFRLLQNSQVFSLIRPNENPAHKSQLVWMACHSAAFEDLRVSSFIRGTRVVPRGQLSTR GVQIASNENTEAMDSNTLELRSRYWAIRTRSGGNTNQQRASAGQISIQPTFSVQRNLPFERATIMAAFTGNTEGRTSDMRTEIIRMMESAR PEDVSFQGRGVFELSDEKATNPIVPSFDMNNEGSYFFGD >gi gb AF _/Avian/5(NP)/... MALQGTKRSYEQMETGGERQNATEIRASVGRMVGGIGRFYIQMCTELKLSDYEGRLIQNSITIERMVLSAFDERRNRYLEENPSAGKDPKK TGGIYKRREGKWVRELILYDKEEIRRIWRQANNGEDATAGLTHLMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAGP AVKGIGTMVMELIRMIKRGINDRNFWRGENGRRTRIAYERMCNILKGKFQTAAQRAMVDQVRESRNPGNAEIEDLIFLARSALILRGSVAHK SCLPACVYGLAVASGYDFEREGYSLVGIDPFRLLQNSQVFSLIRSNENPAHKSQLVWMACHSAAFEDLRVSSFIRGTRVVPRGQLSTRVVQ IASNENMETIDSSTLELRSRYWAIRTRSGGNTNQHRASAGQISVQPTFSVQRSLPFERATIMAAFTGNTEGRTSDMRTEIIRMMESAKPEDV SFQGRGVFELSDEKATNPIVPSFDMNNEGSYFFGDNA
12 Future Research
13 Acknowledgements Takis Benos Department of Computational Biology at the University of Pittsburgh Rachel Brower-Sinning Department of Computational Biology at the University of Pittsburgh
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