A TableDriven, FullSensitivity Similarity Search Algorithm - PowerPoint PPT Presentation

Title: A TableDriven, FullSensitivity Similarity Search Algorithm


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A Table-Driven, Full-Sensitivity Similarity
Search Algorithm

• Gene Myers and Richard Durbin
• Presented by Wang, Jia-Nan and Huang, Yu-Feng

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Outline

• Introduction
• Background
• Preliminary
• Method
• Experiment

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Introduction

• Given a Query and database . Do local alignment
• Smith-Waterman Guaranteed to find all local
  alignment . Expensive
• BLAST
• FASTA

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Improvement

• Hardware more investment on computer ,CPU
• Software
• Phil Greens SWAT appeal to sparsity and some
  machine-level coding tricks
• 60 of dynamic programming matrix has value 0
• Avoiding computing most of these unproductive
  entries

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• Focus on improving protein similarity searches
• This approach examines and compute only 4 of the
  underlying dynamic programming matrix

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Recall

• Sequence alignment
• Local sequence alignment
• Global sequence alignment
• Goal matching path with highest score
• Table-based computation and dynamic programming

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Dynamic Programming

• Three basic components
• Recurrence relation
• Tabular computation
• Traceback

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Smith-Waterman Method

• Dynamic programming algorithm
• Find the most similar subsequences of two
  sequences
• Problem
• Lots of computation ? will be googol
• Programmer ? will be crazy and excite
• Why? ? how to accelerate

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Background

• Scoring System
• Simple scoring scheme
• Affine gap penalty scoring scheme
• PAM120 (PAMn)
• BLOSUM62 (BLOSUMn)

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Simple Scoring Scheme

• Match (e.g. 8)
• Mismatch (e.g. -5)
• Gap constant penalty (e.g. -20)

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Affine Gap Penalty Scoring Scheme

• Match (e.g. 8)
• Mismatch (e.g. -5)
• Gap symbol (e.g. -5)
• Gap open penalty (e.g. -10)

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PAM

• PAM Percent Accepted Mutation
• Dayhoff et al. (1978)
• PAM unit
• Evolutionary time corresponding to average of 1
  mutation per 100 residues ? 1 accepted
• PAMn
• Relates to mutation probabilities in evolutionary
  interval of n PAM units

Some information from http//www.apl.jhu.edu/prz
ytyck/CAMS_2004_1b.pdf
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PAM120
Source http//eta.embl-heidelberg.de8000/misc/ma
t/pam120.html
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BLOSUM62

• BLOSUM BLOcks SUbstitution Matrix
• Steven and Jorga G. Henikoff (1992)
• Paper Amino acid substitution matrices from
  protein blocks PubMed
• BLOSUMn
• Relates to mutation probabilities observed
  between pairs of related proteins that diverged
  so above n identity

Some information from http//www.apl.jhu.edu/prz
ytyck/CAMS_2004_1b.pdf
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BLOSUM62
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Preliminaries

• S sequences are composed
• S S Substitution matrix S giving the score
• Uniform gap penalty g gt 0
• Query q1q2. . .qp of P letters
• Target t1t2. . .tn of N letters
• Threshold T gt 0

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Score Table ? Edit Graph
Picture source http//searchlauncher.bcm.tmc.edu/
help/Pictures/S-Wexample.gif
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Problem

• Find a high score local alignment between Query
  and Target whose path score ?T
• Edit-graph figure1
• Limit our attention to prefix-positive paths
• If there is a path of score T or greater in the
  edit graph then there is a prefix positive path
  of score T or greater

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Definition

• A set P of index-value pairs (i,v) i is 0,P

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The start and extension tables

• Consider a vertex x in row j of the edit graph of
  Query vs. Target

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Start Trimming

• Limiting the dynamic programming to the
  startable vertices requires a table Start(w)
  where w Sks

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Start Trimming

• Worst case
• Let abe the expected percentage of vertices that
  are seed

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Extension Trimming

• A table that eliminates vertices that are not
  extendable
• (i,j) is extendable vertex iff C(i,j)gtExtend(i,Tar
  getj1jke)

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Extension Trimming
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A Table-Driven Scheme for DP

• Goal to restrict the SW computation to
  productive vertices
• Jump table captures the effect of Advance and
  Delete over kJ gt 0 rows
• space ? unmanageably large
• But only record those for which

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• Jump table
• Start table
• Space-saving version for Jump and Start tables

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• Check for paths scoring T or more

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Recall Affine Gap Penalty

• Score
• Match
• Mismatch
• Gap symbol - gsp
• Gap open penalty - gop
• Affine cost of gap of length k
• g kh, g gop, h gsp

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Diagram of Affine Gap Penalty
Source kmchaos lecture note
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• Recurrence system - Gotoh

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The Case of Affine Gap Costs

• Simple scoring scheme ? affine gap penalty scheme
• Affine edit graph and vertex structure
• Question how to modify the equations defined
  above?

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Recurrence System for Affine Gap Costs

• Two observations
• To compute the jth row form the (j-1)st requires
  knowing only the vectors of and values in
  row j-1, and not on the values in that row
• If then the value
  at vertex need not be
  recorded as any maximal path through its
  will have score less than the maximal path
  passing through the corresponding

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Recurrence System
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Results
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Experiment

• Method
• Edit graph based approach vs. SWAT
• Scoring matrix
• PAM120
• Affine gap cost
• 84n
• Database (target)
• 3 million residue subset of the PIR database
• Query
• A periodic clock protein of length 173 (pcp)
• A lactate dehydrogenase of length 319 (dehydro)
• A cGMP kinase of length 670 (kinase)
• A growth factor of length 1210 (g factor)

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PAM120 Gap Cost 84n
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BLOSUM62 Gap Cost 82n
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Ending
Thanks for Your Attention