Proteome Analyst

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Proteome Analyst

• Transparent High-throughput Protein Annotation
  Function, Localization and Custom Predictors

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Proteome Analyst

• Duane Szafron, Paul Lu, Russell Greiner, David
  Wishart, Zhiyong Lu, Brett Poulin, Roman Eisner,
  John Anvik,Cam Macdonell

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Proteome Analyst

• Proteome
• one of many -omes
• set of all proteins in an organism
• Analysis
• prediction of protein function or localization
  from sequence data

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Analyze a Protein

• We have examples of annotated proteins in various
  protein classes.
• We have more examples of unannotated proteins.

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Analyze a Protein

• We have examples of annotated proteins in various
  protein classes.
• We have more examples of unannotated proteins.
• What do we do?

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Analyze a Protein

• We have examples of annotated proteins in various
  protein classes.
• We have more examples of unannotated proteins.
• What do we do?
• Find homologues to each protein and assume
  similar function.

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Analyze a Protein

• We have examples of annotated proteins in various
  protein classes.
• We have more examples of unannotated proteins.
• What do we do?
• Find homologues to each protein and assume
  similar function.
• Find characteristics of each protein that affect
  function.

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Analyzing Proteins

• One Protein?

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Analyzing Proteins

• One Protein?
• Just do it.

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Analyzing Proteins

• One Protein?
• Just do it.
• 5 Proteins?

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Analyzing Proteins

• One Protein?
• Just do it.
• 5 Proteins?
• Post-doc familiar with protein classes.

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Analyzing Proteins

• One Protein?
• Just do it.
• 5 Proteins?
• Post-doc familiar with protein classes.
• 50 Proteins?

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Analyzing Proteins

• One Protein?
• Just do it.
• 5 Proteins?
• Post-doc familiar with protein classes.
• 50 Proteins?
• grad student

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Analyzing Proteins

• One Protein?
• Just do it.
• 5 Proteins?
• Post-doc familiar with protein classes.
• 50 Proteins?
• grad student
• 5000 proteins?

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Analyzing Proteins

• One Protein?
• Just do it.
• 5 Proteins?
• Post-doc familiar with protein classes.
• 50 Proteins?
• grad student
• 5000 proteins?
• summer students

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Proteome Analyst
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Proteome Analyst

• High-throughput
• Transparent
• Prediction of
• Protein Function
• Protein Localization
• Custom Classification

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Machine Learning Task

• Training
• INPUT sequences, classes
• OUTPUT Classifier
• Analysis
• INPUT sequences, Classifier
• OUTPUT classes

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Machine Learning Task

• Training
• INPUT sequences, classes
• OUTPUT Classifier
• Analysis
• INPUT sequences, Classifier
• OUTPUT classes, explanation

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Training

• INPUT
• sequences, classes
• PA Tools
• sequences ? features
• ML Algorithm
• features, classes ? Classifier
• OUTPUT
• Classifier

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Training INPUT

• gtclass AltTraining Seq 1
• MVGSGLLWLALVSCILTQASAVQRGYGN
• PIEASSYGL...
• gtclass BltTraining Seq 2
• LLDEPFRSTENSAGSQGCDKNMSGWYRF
• VGEGGVRMS...
• gtclass BltTraining Seq 3
• EVIAYLRDPNCSSILQTEERNWVSVTSP
• VQASACRNI...
• .
• .
• .

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Training INPUT
classes

• gtclass AltTraining Seq 1
• MVGSGLLWLALVSCILTQASAVQRGYGN
• PIEASSYGL...
• gtclass BltTraining Seq 2
• LLDEPFRSTENSAGSQGCDKNMSGWYRF
• VGEGGVRMS...
• gtclass BltTraining Seq 3
• EVIAYLRDPNCSSILQTEERNWVSVTSP
• VQASACRNI...
• .
• .
• .

protein sequences
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Training PA Tools

• sequences ? features

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Training PA Tools

• sequences ? features
• Homology Tools (BLAST)
• sequence ? homologues
• homologues ? annotations
• annotations ? features

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Homology Tool

• sequence ? features

sequence
seq DB
BLAST
homologues
retrieve
parse
annotations
features
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Homology Tool

• sequence ? features

sequence
DBSOURCE swissprot locus MPPB_NEUCR, ... xrefs
(non-sequence databases) ... InterProIPR001431,..
. KEYWORDS Hydrolase Metalloprotease Zinc
Mitochondrion Transit peptide Oxidoreductase
Electron transport Respiratory chain.
seq DB
BLAST
homologues
retrieve
parse
annotations
features
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Homology Tool

• sequence ? features

sequence
seq DB
BLAST
homologues
retrieve
parse
annotations
features
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Training PA Tools

• sequences ? features
• Homology Tools (BLAST)
• sequence ? homologues
• homologues ? annotations
• annotations ? features
• Pattern Tools (PFAM, ProSite, )
• sequences ? motifs
• motifs ? features

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Pattern Tool

• sequence ? features

sequence
pattern DB
find
patterns
parse
features
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Pattern Tool

• sequence ? features

sequence
pattern DB
find
Pfam PF00234 tryp_alpha_amyl 1. PROSITE
PS00940 GAMMA_THIONIN 1. PROSITE PS00305
11S_SEED_STORAGE 1.
patterns
parse
features
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Pattern Tool

• sequence ? features
• not included in current results

sequence
pattern DB
find
patterns
parse
features
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Training ML Algorithm

• features, classes ? Classifier

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Training ML Algorithm

• features, classes ? Classifier
• any ML Algorithm may be used
• default naïve Bayes
• consistently near-best accuracy
• (SVM, ANN slightly better)
• efficient (for high-throughput)
• easy to interpret

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Training OUTPUT

• Classifier

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Analysis (Classification)

• INPUT
• sequences
• PA Tools
• sequences ? features
• Classifier
• features ? classes, explanation
• OUTPUT
• classes

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Analysis INPUT

• gtSeq 1
• DTILNINFQCAYPLDMKVSLQAALQPIV
• SSLNVSVDG...
• gtSeq 2
• AVELSVESVLYVGAILEQGDTSRFNLVL
• RNCYATPTE...
• gtSeq 3
• HVEENGQSSESRFSVQMFMFAGHYDLVF
• LHCEIHLCD...
• .
• .
• .

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Analysis INPUT

• gtSeq 1
• DTILNINFQCAYPLDMKVSLQAALQPIV
• SSLNVSVDG...
• gtSeq 2
• AVELSVESVLYVGAILEQGDTSRFNLVL
• RNCYATPTE...
• gtSeq 3
• HVEENGQSSESRFSVQMFMFAGHYDLVF
• LHCEIHLCD...
• .
• .
• .

protein sequences
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Analysis PA Tools

• sequences ? features

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Analysis PA Tools

• sequences ? features
• Homology Tools (BLAST)
• sequence ? homologues
• homologues ? annotations
• annotations ? features
• Pattern Tools (PFAM, ProSite, )
• sequences ? motifs
• motifs ? features

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Analysis Classification

• features ? classes

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Analysis Classification

• features ? classes
• naïve Bayes
• returns probabilities of each class for each
  sequence
• efficient (for high-throughput)
• easy to interpret

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Analysis Classification

• features ? classes, explanation

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Analysis Classification

• features ? classes, explanation

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Analysis Classification

• features ? classes, explanation

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Analysis Classification

• features ? classes, explanation

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Analysis Classification

• features ? classes, explanation

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Results General Function

• GeneQuiz classification
• 5-fold x-val accuracy on 14 classes

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Results General Function

• GeneQuiz classification
• 5-fold x-val accuracy on 14 classes

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Results Specific Function

• K Ion Channel Proteins
• 5-fold x-val accuracy on
• 78 sequences, 4 classes

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Results Specific Function

• K Ion Channel Proteins
• 5-fold x-val accuracy on
• 78 sequences, 4 classes

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Results Localization

• Sub-cellular localization prediction
• 3146 sequences from 10 classes

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Results Localization

• Sub-cellular localization prediction
• 3146 sequences from 10 classes

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Results

• Sub-cellular localization prediction
• 3146 sequences from 10 classes

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Proteome Analyst

• High-throughput
• Transparent
• Prediction of
• Protein Function
• Protein Localization
• Custom Classification

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Acknowledgements

• Student developers
• Cynthia Luk
• Samer Nassar
• Kevin McKee
• Biologists
• Warren Gallin
• Kathy Magor
• Data
• Nair and Rost

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Acknowledgements

• Funding
• PENCE Protein Engineering Network of Centres of
  Excellence
• NSERC - National Science and Engineering Research
  Council
• Sun Microsystems
• AICML - Alberta Ingenuity Centre for Machine
  Learning

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Acknowledgements

• Many -ome jokes
• my wife, Jen

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Contact

• http//www.cs.ualberta.ca/bioinfo/PA
• poulin_at_cs.ualberta.ca