Information-Theoretic Mass Spectral Library Search

1
Outline Introduction Related Work Method Results
and Discussion
Information-Theoretic Mass Spectral Library
Search
Arvind Visvanathan CSCE 990 Seminar in
Multi-Dimensional Chromatography Systems,
Informatics, and Applications
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
2
Outline Introduction Related Work Method Results
and Discussion
Outline

• Introduction
• Mass spectrum search types
• Related Work
• Other techniques
• NIST, PBM, DotMap
• Method
• Probability and Information
• Normalized distribution function
• Results
• Conclusion

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
3
Mass Spectrum Search Algorithm Search
Types Applications
Outline Introduction Related Work Method Results
and Discussion
Introduction Mass Spectrum
Decane
Intensity
m/z
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
4
Outline Introduction Related Work Method Results
and Discussion
Mass Spectrum Search Algorithm Search
Types Applications
Introduction Mass Spectrum Search
Unknown Spectrum
Search Algorithm
Potential Matches
MS Library
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
5
Mass Spectrum Search Algorithm Search
Types Applications
Outline Introduction Related Work Method Results
and Discussion
Introduction Search Types

• Identity search
• Unknown mass spectrum present in library
• Looking for exact spectrum
• Similarity search
• Unknown mass spectrum not present in library
• Looking for similar spectrum

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
6
Mass Spectrum Search Algorithm Search
Types Applications
Outline Introduction Related Work Method Results
and Discussion
Introduction MS Search Applications

• Steroid detection in athletes
• Monitor patient breath during surgery
• Composition of molecular species found in space
• Honey adulterated with corn syrup
• Locate oil deposits
• Monitor fermentation process in the biotechnology
  industry
• Detect dioxins in contaminated fish

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
7
MS Search Probability Based Matching DotMap
Outline Introduction Related Work Method Results
and Discussion
Related Work NIST MS-Search Stein 94

• Pre-search the unknown spectra in library
• Reduce search domain (160K ? 4K compounds)
• Compute match factor for each compound in the
  pre-search result
• Match Factor (MF)
• Range 0-999
• Higher the better
• Pre-search result sorted based on MF value
• Pick the topmost compounds as possible matches

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
8
MS Search Probability Based Matching DotMap
Outline Introduction Related Work Method Results
and Discussion
Related Work NIST MS-Search Stein 94

• Match Factor Computation Stein 94
• Term 1 Mass weighted normalized dot product
• Term 2 Relative intensities of adjacent peaks
  in both spectra
• Combination of F1 F2

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
9
MS Search Probability Based Matching DotMap
Outline Introduction Related Work Method Results
and Discussion
Related Work NIST MS-Search Stein 94
C-1
C-2
m/z Intensity
35 100
36 1
37 2
45 999
55 200
m/z Intensity
35 100
36 1
37 1
45 999
55 200
Compare C-1 C-1 Compare C-1 C-2
F1 999 999
F2 999 824
MF 999 925
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
10
Outline Introduction Related Work Method Results
and Discussion
MS Search Probability Based Matching DotMap
Related Work Probability Based Matching
McLafferty et. al. 75

• Confidence Value (K) instead of MF
• Four components for each m/z
• Term 1 U Based on the uniqueness of a m/z
  value
• Term 2 A Intensity contribution to the
  confidence
• Term 3 W Window factor (measure of agreement)
• Term 4 D Dilution factor (measure of purity)
• K ? ? (U A W D) for each m/z

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
11
Outline Introduction Related Work Method Results
and Discussion
MS Search Probability Based Matching DotMap
Related Work DotMap Sinovec et. al. 04
Fumaric acid
Adipic acid
DotMap
Lactic acid
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
12
Outline Introduction Related Work Method Results
and Discussion
MS Search Probability Based Matching DotMap
Related Work DotMap Sinovec et. al. 04

• Inverse problem
• DotMap computed across the image
• Higher valued areas indicate presence of compound
  of interest
• Multiple compounds of interest
• Compute DotMap overlay

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
13
Outline Introduction Related Work Method Results
and Discussion
MS Search Probability Based Matching DotMap
Related Work DotMap Sinovec et. al. 04
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
14
Outline Introduction Related Work Method Results
and Discussion
MS Search Probability Based Matching DotMap
Related Work DotMap Sinovec et. al. 04
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
15
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Motivation

• NIST MS-Search Stein 94
• No domain information utilized
• PBM Matching McLafferty et. al. 75
• Old technique (75)
• Ad hoc domain information utilization
• DotMap
• No domain information utilized

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
16
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Entropy

• Entropy based approach
• Entropy ? measure of the amount of uncertainty
• Based on probabilities
• Include domain based knowledge (information) in
  computing the match factor

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
17
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Distribution Function

• Library
• NIST EPA Library
• 163K compounds
• Compute distribution function (DF)
• 2 dimensional array
• m/z vs intensity
• DFij
• compounds in library
• m/z i
• Intensity j

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
18
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Distribution Function
Intensity
m/z
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
19
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Normalized Distribution Function (NDF)

• Normalized Distribution Function
• NDFmzint DFmzint / ? DFmzi
• Where ? DFmzi 163K
• NDF ? Probabilities 0-1

i
i
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
20
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Assumptions

• Assumption
• Each m/z is treated independently in the match
  factor computation from normalized distribution
  function

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
21
Motivation Probability Entropy Distribution
Function Match Factor
Outline Introduction Related Work Method Results
and Discussion
Method Match Factor
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
22
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Overview

• Technique
• Compound in library Noise
• Search noisy compound in library
• Evaluation metric - Average Rank
• Rank Position of correct compound in hit list
• Repeat above 3000 times and take average rank
• Compared with
• NIST
• NISTDOT (First term in NIST algorithm)

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
23
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Noise models

• Additive
• AU AL G(0,s)
• Multiplicative
• AU AL AL G(0,s)
• Johnson Colored
• AU AL G(0,svm)
• Random spectrum
• AU AL x AR

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
24
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Additive Noise

• Compound Compound Additive noise
• Additive Gaussian noise
• Zero mean
• Variable standard deviation
• For each m/z in library spectrum
• AU AL G(0,s)

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
25
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Additive Noise (Example)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
26
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Additive Noise (Performance)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
27
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Multiplicative Noise

• Compound Compound Multiplicative noise
• Multiplicative Gaussian noise
• Zero mean
• Variable standard deviation
• For each m/z in library spectrum
• AU AL AL G(0,s)

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
28
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Multiplicative Noise (Example)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
29
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Multiplicative Noise (Performance)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
30
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Johnson Colored Noise

• Compound Compound Colored Noise
• Gaussian noise
• Zero mean
• Variable standard deviation
• For each m/z in library spectrum
• AU AL G(0,svm)

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
31
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Johnson Colored Noise (Example)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
32
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Johnson Colored Noise (Performance)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
33
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Random Spectrum Noise

• Compound Compound Random Spectrum
• Additive Spectrum
• Add x of another random spectrum
• For each m/z in library or random spectrum
• AU AL x AR

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
34
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Random Spectrum Noise (Example)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
35
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Random Spectrum Noise (Performance)
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
36
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Summary of Noise Models

• Additive
• AU AL G(0,s)
• Multiplicative
• AU AL AL G(0,s)
• Johnson Colored
• AU AL G(0,svm)
• Random Spectrum
• AU AL x AR

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
37
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Summary of Noise Models
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
38
Overview Additive Noise Multiplicative
Noise Johnson Colored Noise Random Spectrum Noise
Outline Introduction Related Work Method Results
and Discussion
Results Summary of Noise Models
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
39
Outline Introduction Related Work Method Results
and Discussion
Conclusion

• MS library search algorithm
• Information theoretic
• Domain knowledge incorporated
• Algorithm works well for various noise models
• Future work
• Must improve performance for the random spectrum
  noise case

Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar
40
Outline Introduction Related Work Method Results
and Discussion
Questions Suggestions
?
Information-Theoretic Mass Spectral Library Search
CSCE 990 GCxGC Seminar