Smart Templates for Chemical Identification in GCxGC-MS

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Smart Templates for Chemical Identification in
GCxGC-MS

• QingPing Tao1, Stephen E. Reichenbach2,
• Mingtian Ni3, Arvind Visvanathan2, Michael Kok2,
  Luke L. Waltman1
• 1GC Image, LLC, Lincoln, NE
• 2Computer Science Engineering Dept., University
  of Nebraska-Lincoln
• 3Microsoft Corp., Redmond, WA

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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GCxGCPeak Template MatchingSmart
TemplatesBuilding Smart Multi-type
TemplatesConclusions and Future Work
Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
GCxGC Objective of GCxGC Analysis Chemical
Identification Outline
GCxGC

• Two independent separations for the entire sample
• GCxGC data can be processed as a digital image
• Mass spectrometry (MS) data provides rich
  information for identification

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
GCxGC Objective of GCxGC Analysis Chemical
Identification Outline
GCxGC
GC Chromatogram
GCxGC Total Ion Chromatogram
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
GCxGC Objective of GCxGC Analysis Chemical
Identification Outline
Objective of GCxGC Analysis

• Separate individual peaks from background
• Quantify each peak
• Identify the peaks for chemicals of interest

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
GCxGC Objective of GCxGC Analysis Chemical
Identification Outline
Chemical Identification with GCxGC

• Automated approaches
• Library search
• Such as NIST Mass Spectral Library
• Rule-based techniques
• Such as constrain expressions based on retention
  times or mass spectrum
• Pattern matching markers, chemical retention
  pattern.
• Challenges
• Data inconsistencies retention time variations
• Data and task complexities multi-dimension, many
  peaks
• Solution combined approach (Smart templates)
  with peak template matching constraint
  expressions

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
GCxGC Objective of GCxGC Analysis Chemical
Identification Outline
Outline

• Peak template matching
• Smart Templates
• Computer Language for Identifying Chemicals
  (CLIC)
• Smart Template
• Peak template matching with CLIC
• Building Smart Multi-type Templates
• Interactive tools for building smart multi-type
  templates
• Automatically generating CLIC for peaks
• Automatically generating peak sets with markers.
• Conclusion and Future Works

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Chemical Identification Process Fundamental
Difficulty
Peak Template Matching

• Identify compounds by matching previously known
  peaks to unidentified peaks
• A peak template is a set of annotated peaks with
• Computed features such as peak location (2D
  retention times)
• Assigned information such as compound name
• A target peak is a set of unannotated peaks that
  have computed features
• Peak template matching tries to establish as many
  correspondences as possible from template peaks
  to target peaks

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Chemical Identification Process Fundamental
Difficulty
Chemical Identification Process

• Construct a peak template
• Created by a chemist through interactive
  annotation
• Match template and target peaks
• Apply the template assign information from
  template to target peaks

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Chemical Identification Process Fundamental
Difficulty
Fundamental Difficulty of Peak Template Matching

• Peak pattern distortions
• Peaks for the same compound may appear at
  different retention times in different images
• Basic solution
• Search all allowable matches from template peaks
  to target peaks under some retention time windows
  
• Find a transformation that maximize the number of
  matched peaks

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Chemical Identification Process Fundamental
Difficulty
Fundamental Difficulty of Peak Template Matching

• Challenges
• Searching transformations in a large space is
  computationally expensive
• False identifications may happen when two target
  peaks are very close together
• A solution Smart Template

peak2
B2
peak1
B1
B3
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Computer Language for Identifying Chemicals
(CLIC) Example CLIC Expressions Peak Template
Matching with CLIC
Smart Templates

• Objective
• Reduce the number of allowable matchings
• Reduce ambiguous matchings
• Reduce human intervention
• Approach
• Add more constraints other than retention time
  patterns
• CLIC

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Computer Language for Identifying Chemicals
(CLIC) Example CLIC Expressions Peak Template
Matching with CLIC
Computer Language for Identifying Chemicals (CLIC)

• CLIC Reichenbach et al., 2004 is a language to
  express constraints on GCxGC retention times,
  peak characteristics, and mass spectral
  characteristics
• Functions of retention times
• Functions of peak characteristics
• Functions of mass spectra
• Logical and arithmetic operators
• Comparative operators lt, , gt, , , ?
• Addition, subtraction, negation (-) and
  parentheses
• Logical operators and(), or (), and negation(!)

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Computer Language for Identifying Chemicals
(CLIC) Example CLIC Expressions Peak Template
Matching with CLIC
Computer Language for Identifying Chemicals (CLIC)

• Functions characterizing chromatographic
  properties and mass spectral characteristics are
  key features of CLIC.
• Retention(2) returns the retention time of the
  peak on the second column.
• Intensity(40) returns the intensity value of the
  indicated channel (m/z 40) in the mass spectrum
  of the peak.
• Ordinal(40) returns the ordinal position of the
  indicated channel (m/z 40 in a mass spectrum)
  in the intensity-ordered multi-channel array of
  the peak.

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Computer Language for Identifying Chemicals
(CLIC) Example CLIC Expressions Peak Template
Matching with CLIC
Example CLIC Expressions

• Alkanes
• Criteria (Welthagen et al. 2003) Base peak 57
  or 71 and second largest peak 71 or 57. No time
  rule is needed for this group, but a retention
  window of 1.0 1.5s can be used.
• CLIC Expression
• (Ordinal(57) 2) (Ordinal(71) 2)
  (Retention(2) 1.0) (Retention(2) 1.5)

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Computer Language for Identifying Chemicals
(CLIC) Example CLIC Expressions Peak Template
Matching with CLIC
Peak Template Matching with CLIC

• Each peak in the template has an optional CLIC
  expression
• First, find a set of possible matches by using
  the retention time pattern
• Then, prune the matching space based on CLIC
  expressions
• Finally, search for the best matching
• The combination of chromatographic retention time
  patterns and CLIC expressions can improve both
  speed and accuracy of automated chemical
  identification for GCxGC
• We call it a Smart template

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Building Smart Multi-type Templates

• Smart Template has been implemented in GC Image
  software.
• Interactive tools for building Multi-type
  Templates
• Peaks, groups, graphics, text objects and
  chemical structures
• Interactive tools for building CLIC expressions
• A GUI that resembles a calculator for users to
  create and test CLIC expressions
• An interface for specifying a CLIC expression for
  each template peak
• Interfaces to match and apply templates

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Build Multi-type template
Construct and edit template with peaks and other
structures
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Build Smart Template Example with Grob Mix
1) Build a template from the original image
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Build Smart Template Example with Grob Mix
2) Wrong match because of peak pattern
distortions
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Build Smart Template Example with Grob Mix
3) Smart template solution a) Create CLIC
expression for Nonanal
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Build Smart Template Example with Grob Mix
b) Specify CLIC expression for Nonanal template
peak
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Build Smart Template Example with Grob Mix
4) Matching with Smart Template
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Auto CLIC

• Automatically generate CLIC expressions for
  peaks
• CLIC function Match()
• NIST matching function returns the similarity
  between two mass spectra
• Value range is 0, 1000
• Higher is the value, more similar are the two
  mass spectra
• CLIC expression, Match(ltmsgt) gt threshold,
  can be used to identify chemicals.
• The mass spectrum of the peak is ltmsgt
• Automatically generate the threshold

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Auto CLIC

• Automatically generate matching threshold
• The similarities between this peak and all other
  peaks should be less than the threshold
• The threshold has the large margins from this
  peak and all other peaks
• For example peak 1 represents blob B1
• B1. Match(ltB1s MSgt) 1000
• B2. Match(ltB1s MSgt) 600
• B3. Match(ltB1s MSgt) 400
• Match(ltB1s MSgt) gt 800

B1
peak1
B2
800
B2
B3
B1
B3
600
1000
400
0
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Auto CLIC
1) Set Auto CLIC function
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
Template Auto CLIC Auto chemical grouping with
markers
Auto CLIC
2) Generate CLIC
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Auto chemical grouping with markers

• Group peaks based on their retention time
  patterns
• Build natural clusters of peaks
• Each cluster is represented by a polygon
• A template may consist of a set of groups
  (polygons)

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Auto chemical grouping with markers
29 clusters created by single linkage
hierarchical clustering algorithm
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Auto chemical grouping with markers

• Automatically generate markers for groups
  (polygons)
• Template matching is based on peaks
• Each group needs markers
• A marker is a significant peak in the group
• Markers are at evenly distributed locations to
  represent the retention time pattern of the group
• Auto marker
• Cluster all peaks in a group
• Pick the largest peak in each cluster as a marker

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
31
Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Auto chemical grouping with markers

• 1) Set Auto Marker function

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
32
Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Auto chemical grouping with markers

• 2) Generate markers

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
33
Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Build Multi-type template Build Smart
template Auto CLIC Auto chemical grouping with
markers
Auto chemical grouping with markers

• 2) Generate markers

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Smart
Templates Building Smart Multi-type
Templates Conclusions and Future Work
Conclusions and Future Work

• Smart Template matching can be used to
  automatically identify chemicals in GCxGC-MS data
• The combination of retention time patterns and
  constraints greatly reduces ambiguity and speeds
  processing
• Future work
• Enhanced GUI
• More CLIC functions
• Semi-automated or automated template construction
• Auto CLIC and Auto Marker are just two first
  steps

Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS
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Introduction Peak Template Matching Computer
Language for Identifying Chemicals Peak Template
Matching with CLIC Conclusions and Future Work
Current work is supported by NSF and
NIH Questions? Software info_at_gcimage.com
www.gcimage.com Licensing
info_at_zoex.com www.zoex.com
Q. Tao, S. E. Reichenbach, et al.
Multi-type Templates in GCxGC-MS