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Overview

Paracel GeneMatcher2

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GeneMatcher2

• The GeneMatcher system comprises of hardware and software components that significantly accelerate a number of computationally intensive sequence similarity search algorithms.

• There are two hardware components:– GeneMatcher accelerator– Post-Processor (Blastmachine)

• Two client intefaces:– Unix command line– Web-based GUI (BioView Workbench)

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GeneMatcher2 Architecture

GeneMatcher2 Blast machine

Switch

CPU 1 CPU 2 CPU 6912...

Query #1 (agaggt..)

a g a

Query #n...

Web interface

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GeneMatcher2 System

• Massively Parallel Bioinformatics supercomputer• Array of ASIC (Application Specific Integrated Circuit)

chips combined with state-of-the-art Linux cluster technology

• Accelerates dynamic programming search algorithms• 3,000 to 220,000 processors• Thousands of times faster than general purpose

computers

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3 Processor units(6,142 processors

per unit)

Up to 4 disk drivesFor database storage

ULTRASparccomputer

GeneMatcher2 Components

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GeneMatcher2 Algorithms

• HMM and HMM-Frame– Searches protein or DNA sequence data with domain models– HMM-Frame aligns protein models to DNA with frame shift

and optional intron tolerance

• Profile and Profile-Frame– Position-specific scoring with profile models– Frame shift tolerant protein profile searches against DNA

sequence data

• GeneWise– Aligns protein sequences or HMM against genomic data– Tolerates introns and frame shifts

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GeneMatcher2 Algorithms cont,

• Smith-Waterman– Comparison of DNA-DNA, Protein-Protein, Protein-DNA or

DNA-DNA through protein– Frame algorithms tolerate frame shifts, unlike BLAST

counterparts– Optional intron tolerance for searches of genomic data– Highly sensitive search capacity finds hits BLAST

potentially misses– NCBI Blast

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• Blast is an approximation of Smith-Waterman • So is FastA, but it's better and has protein fragment

searches • Approx. may not yield correct results in some situations:

– Data with many ambiguities or frameshifts, such as raw ESTs and unfinished genomic sequence

– Distantly related sequences– When global alignments are desired– Protein alignment of Sequences with introns (not penalized on

GeneMatcher)

What about Blast?

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•Comparison of sensitivity and selectivity of various sequence search methods

•Sensitivity: What proportion of the real hits are reported? (More sensitive means more real hits)•Selectivity: What proportion of the reported hits are real? (More selective means less false positives)

Why GeneMatcher2

Less Falsepositives

More true positives

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GeneMatcher2 Performance•Time-to-completion comparison of original methods and methods on GeneMatcher2

•TBLASTX improvement is 20-fold•Other methods at least 100-fold improvement

Source: Genome Canada Bioinformatics Platform Project

NCBI TBLASTX

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270

1000

Runtime for an average query

Method

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400

600

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* * *

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• Load a sequence (or set of sequences) as a query set if it will be used several times

• Select the appropriate search depending on the query type and database type (only suitable candidates will be displayed on the search forms)

• Check your form options!• Watch the search queue (can raise priority of small

jobs if machine is busy)• Select a result format

Running a search

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• While you can load your own databases, disk space on the post-processor is not infinite! Ask us about maintaining public databases that are not currently available.

• If you upload a private database. Special files need to be created to use translated database searches such as rframe.

• You can create private data sets to search against (e.g. Unigene-mouse and Unigene-rat in a data set called Unigene-rodent). These don’t take up any space.

Databases

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Hidden Markov Models

THE LAST FAST CAT+++ ++++ ++++ +++ all matches

“AST” from LAST “V” from VERY

}

Multiple sequence alignment(Clustalw or T-coffee)

THE LAST FAT CATTHE FAST CATTHE VERY FAST CATTHE FAT CAT

Seq 1Seq 2Seq 3Seq 4

Positive examples

THE LAST FA T CATTHE FAST CATTHE VERY FAST CATTHE FA T CATTHE LAST FAST CAT orororor or

VERY gap gapgapgap

Position specificPositive examples

THE VAST FAST CATQuery

HMM Build

Hidden MarkovModel

GeneMatcher2

THE VAST VERY FAST CATQuery

Only nothing, “LAST” or “VERY”in that position

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• Predict introns and exons based on conserved protein domains (e.g Pfam database)

• Uses HMMs, reverse query/data set relationship holds

• Unlike genscan or fgenes, you can believe these hits, though they may not be complete where exons don’t contain conserved domains.

GeneWise