Profiles and different Arrangement arrangements.

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Substance. Characterizing profilePSSM by PSI-BLASTProfile HMMAligning profilesPSSM
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Profiles and numerous Sequence arrangements Understanding Bioinformatics 9 th KIAS winter school Lee, Juyong

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Contents Defining profile PSSM by PSI-BLAST Profile HMM Aligning profiles PSSM & Profile HMM Generate different succession arrangement Progressive Other strategies

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What is Profile? Speak to general properties of the arrangement of sequences An arrangement of successions contains more data than a solitary grouping Environment is being viewed as Two sorts P osition S pecific S coring M atrix Profile Hidden Markov Model

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Example PSSM

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Position particular scoring network $> blastpgp - b 0 - j 3 - h 0.001 - d myDB –I mySEQ.fasta –Q myPSSM.mtx –o myMSA.bla

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An arrangement of successions has more data Are K, I and S are significant? Are A & T are useless? K, I and S are profoundly saved! T at the 6th segment is likewise rationed 2 nd and 4 th sections don\'t indicate inclination K-IAS- - KAI-ST-K-I-ST-KRISS- - K-I-STI K-IAS-KAI-ST

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Generating PSSM Log-chances score of amino corrosive an at position u Multiple succession arrangement Lack of data ought to be dealt with! Not Good ! On the off chance that an is not watched, m  - ∞

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Generating PSSM (2) Pseudo-checks : part of amino corrosive an at position u : amino corrosive a conveyance α & β are scaling parameters

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Generating PSSM (3) More reasonable pseudocounts Use substitution network data as opposed to arbitrary arrangement! Pseudo tally of amino corrosive a F : recurrence of amino corrosive b at u Formula utilized as a part of PSI-BLAST

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Example of Pseudocount

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PSI-BLAST is grouping DB looking system Goal : Find arrangement homologs! In the first place, perform consistent BLAST nearby pursuit Build PSSM taking into account the first round result Align arrangements against PSSM Update grouping arrangement! Do these iteratively!

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Sequence Logo

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Profile HMM Represent general property of an arrangement of groupings in view of Hidden Markov Model 0.4 0.1 0.6 0.5 0.7 0.4 0.2 0.7 0.3 0.6 Emit Amino corrosive

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Profile HMM (2) KIA-S-K-AIST KI- - ST KIA-S-K-AIST D1 D2 D3 D4 Start M1 M2 M3 M4 END I0 I1 I2 I3 I4 A S K T I

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Profile HMM (3) KIA-S-K-AIST KI- - ST KIAS-KI-ST D1 D2 D3 D4 Start M1 M2 M3 M4 END I0 I1 I2 I3 I4 I S T K

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Estimate probabilities Transition likelihood between states Amino corrosive emanation likelihood

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Profile HMM requires a great deal of information Many parameters to be prepared Transition probabilities ~ N seq * 9 Amino corrosive outflow probabilities ~ N seq * 20 For 100 buildup seq, ~3000 parameters to be tuned Generally no less than 20~30 related successions are required to construct precise profile HMM

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Many conceivable ways! We have to score them… … QUERY : KRISS D1 D2 D3 D4  Start M1 M2 M3 M4 END Start M1 M2 M3 M4 END I0 I1 I2 I3 I4 I0 I1 I2 I3 I4 S R I S K R 

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How to score an arrangement to profile HMM Two methods for assessing wellness of a grouping to profile HMM Through the Most plausible way Viterbi calculation Faster, less exact Consider every single conceivable way ! Forward ( Backward ) calculation Slower, more exact

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Viterbi calculation Equivalent to the dynamic programming of pairwise arrangement

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Forward calculation Consider all conceivable way ! Likelihood of emanating x i at state S u

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Summary Profile  General property of an inquiry succession got from an arrangement of related groupings Position particular Scoring Matrix Profile Hidden Markov Model Can discover remote succession homolog Those can not be recognized by pairwise arrangement of arrangements

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Aligning Profiles Comparing PSSM LAMA : no holes permitted, use Pearson relationship of scores Prof_sim : holes permitted, use amino corrosive appropriation at every section COMPASS : crevices permitted, psuedocounts are utilized as like PSI-BLAST

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Aligning profile HMMs COACH, HHsearch are accessible Can discover exceptionally remote homologs Position subordinate hole scoring is conceivable

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Multiple Sequence Alignment - MSA

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Why MSA is troublesome? DP of Pairwise is simple and appropriate Only three cases If three groupings… … Seven cases… … For six arrangements… … 60TB memory required DP is Impossible  An A - An A V - V - V L - L

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Methods to adjust successions Progressive technique Add a succession at once ClustalW, T-COFFEE, and so forth. Iterative technique Deletion, realigning steps are presented Prrp, DIALIGN, MUSCLE and so on

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Order is vital! Case 1 Let\'s adjust the followings - D-G D-G-D  - G-G- - G-G D-G-G D-G-G- - Case 2 D G-G D-G-D 

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Determine request ! Fabricate phylogenic tree taking into account all pairwise separation network

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Which MSA is better? - Scoring plan Usually Sum of Pairs are utilized

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Scores ClustalW Similar to plans for pairwise arrangement Employ deposit particular crevice opening

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Scores (2) T-COFFEE Score if adjusted section is available in the Library Diverse arrangement Local & Global

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Library Extension of T-COFFEE Different Weights for individual segments

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Other techniques - DIALIGN Construct entire arrangement from ungapped nearby arrangements Find all ungapped arrangements and weight them ! Key Idea : pairwise arrangement can miss organically essential area

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Other strategies - SAGA Genetic Algorithm Alignment  era Evolve through transformation & Crossover

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Other techniques - MSACSA

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Thank you!

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