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Connectome Classification:
     Statistical Connectomics for
    Analysis of Connectome Data

        Joshua T. Vogelstein, PhD
        d: Applied Math. & Stats
        u: Johns Hopkins
        w: jovo.me
        e: joshuav@jhu.edu
Statistical Connectomics

  Statistics   “the art of data collection and analysis”

Connectomics “the study of connectomes”
  Statistical “the art of connectome data collection
Connectomics and analysis”
Contributors
         Stats
   Carey E. Priebe        Data Collection
 Glen A. Coppersmith       Susan Resnick
    Mark Dredze

Connectome Inference
    Will R. Gray               Wisdom
    John Bogovic          R. Jacob Vogelstein
     Jerry Prince


          Support: various grants
Simplest. Example. Ever.
Blind People        Deaf People

    V1                  V1




  A1 M1              A1 M1
Simplest. Example. Ever.
Blind People                            Deaf People

    V1          No possible classifier       V1
                   based on graph
               invariants can perform
                 this insanely simple
                     classification
  A1 M1                                  A1 M1
                      problem!!!
Realest. Example. Ever.
MR Connectome Gender Classification


 statistical graph model   graph invariants

    > 83% accuracy         < 75% accuracy
Statistical              Connectomics
1. Collect Data                  Multi-Modal MR Imaging
2. Preprocess Data              MR Connectome Pipeline
3. Assumptions                       Signal Subgraph
4. Construct a Decision Rule   Robust Bayes Plugin Classifier
5. Evaluate Performance        Leave-One-Out X-Validation
6. Check Assumptions              Synthetic Data Analysis
7. Extensions                       Relax assumptions
Statistical              Connectomics
1. Collect Data                  Multi-Modal MR Imaging
2. Preprocess Data              MR Connectome Pipeline
3. Assumptions                       Signal Subgraph
4. Construct a Decision Rule   Robust Bayes Plugin Classifier
5. Evaluate Performance        Leave-One-Out X-Validation
6. Check Assumptions              Synthetic Data Analysis
7. Extensions                       Relax assumptions
1. Collect Data:
  Multi-Modal MR Imaging

• 49 senior individuals; 25 male, 24 female
 • diffusion: standard DTI protocol
 • structural: standard MPRAGE protocol
2. Preprocess Data:
MR Connectome Automated Pipeline


• coherent collection of code
• fully automatic and modular
• about 12 hrs/subject/core
• yields 70 vertex graph/subject


        http://www.nitrc.org/projects/mrcap/
3. Data Assumptions:
   Signal Subgraph
4. Construct a Decision Rule:
Robust Bayes Plugin Classifier

• asymptotically optimal and robust
• finite sample niceness
         
                  auv                   1−auv
 y=
 ˆ               puv|y (1
                 ˆ          − puv|y )
                              ˆ                 πy
                                                ˆ
             ˆ
       (u,v)∈S
5. Evaluate Performance:
    Leave-One-Out X-Validation
                                      incoherent estimator                                                  coherent estimator
                                                                                                                                      0.5
misclassification rate




                                                                                   # signal−vertices
                          0.5 L π
                              ˆˆ     = 0. 5                        ˆ
                                                                   L n b = 0. 41                                 ˆ
                                                                                                                 L c o h= 0. 16
                                                                                                       10                             0.4

                         0.25                                                                          20                             0.3
                                              ˆ
                                              L i n c= 0. 27

                                                                                                       30
                            0 0                1               2               3
                                                                                                                                      0.16
                            10             10          10       10                                           200 400 600 800 1000
                                    log size of signal subgraph                                           size of signal subgraph
                                     some coherent estimators                                          zoomed in coherent estimator
                                                                                                                                      0.5
lassification rate




                          0.5
                                                                                   star−vertices




                                                                                                       15
                                                                                                                                      0.4
                                                                                                       18
                         0.25                                                                                                         0.3
                         0.16                                                                          21
6. Check Assumptions:
Synthetic Data Analysis
                 Correlation Matrix
                                       1


           100                         0.5
  vertex




                                       0
           200

                                       −0.5
           300

                                       −1
                  100     200    300
                        vertex
7. Extensions


• relax the independent edge assumption
• relax binary edge assumption
Discussion


• 83%  75%
• yay statistical modeling!
Q(A)


• anything?
4. Construct a Decision Rule:
 Signal Subgraph Estimation
 •   for each edge, we compute the significance of
     the difference between the two classes using
     Fisher’s exact test
 •   the incoherent signal subgraph estimator finds
     the s edges that are most significant
 •   the coherent signal subgraph estimator finds the
     s edges that are most significant incident to m
     vertices
4. Construct a Decision Rule:
 Signal Subgraph Estimation

                   negative log                       incoherent                    coherent
                significance matrix                    estimate                     estimate




                                                                   # correct = 15
                                      # correct = 7
           20
  vertex
  n=64




           40

           60

                   20    40    60                                                              −4.4   −1.
                      vertex
6. Check Assumptions:
                                          incoherent estimator                                                     coherent estimator
                              1
misclassification rate




                                                                                   # star−vertices
                         0.75                                                                                                                             0.7
                                                                                                       10



                         0.25
                             0.5
                                       Synthetic Data Analysis                                         20                                                 0.5


                                                                                                       30                                                 0.3
                              0                                                                                                                           0.18
                                0                 1            2          3                                        200     400    600   800 1000
                              10                10         10           10
                                       log size of signal subgraph                                               size of signal subgraph

                              1                                                                        0.5




                                                                              misclassification rate
          missed−edge rate




                                                                                                                                                    coh
                                                                                                       0.4                                          inc
                                                                                                       0.3                                          nb
                             0.5
                                                                                                       0.2

                                                                                                       0.1

                              0
                                   0     20          40   60       80   100                                  0       20          40     60     80         100
                                              # training samples                                                          # training samples

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Connectome Classification: Statistical Connectomics for Analysis of Connectome Data

  • 1. Connectome Classification: Statistical Connectomics for Analysis of Connectome Data Joshua T. Vogelstein, PhD d: Applied Math. & Stats u: Johns Hopkins w: jovo.me e: joshuav@jhu.edu
  • 2. Statistical Connectomics Statistics “the art of data collection and analysis” Connectomics “the study of connectomes” Statistical “the art of connectome data collection Connectomics and analysis”
  • 3. Contributors Stats Carey E. Priebe Data Collection Glen A. Coppersmith Susan Resnick Mark Dredze Connectome Inference Will R. Gray Wisdom John Bogovic R. Jacob Vogelstein Jerry Prince Support: various grants
  • 4. Simplest. Example. Ever. Blind People Deaf People V1 V1 A1 M1 A1 M1
  • 5. Simplest. Example. Ever. Blind People Deaf People V1 No possible classifier V1 based on graph invariants can perform this insanely simple classification A1 M1 A1 M1 problem!!!
  • 6. Realest. Example. Ever. MR Connectome Gender Classification statistical graph model graph invariants > 83% accuracy < 75% accuracy
  • 7. Statistical Connectomics 1. Collect Data Multi-Modal MR Imaging 2. Preprocess Data MR Connectome Pipeline 3. Assumptions Signal Subgraph 4. Construct a Decision Rule Robust Bayes Plugin Classifier 5. Evaluate Performance Leave-One-Out X-Validation 6. Check Assumptions Synthetic Data Analysis 7. Extensions Relax assumptions
  • 8. Statistical Connectomics 1. Collect Data Multi-Modal MR Imaging 2. Preprocess Data MR Connectome Pipeline 3. Assumptions Signal Subgraph 4. Construct a Decision Rule Robust Bayes Plugin Classifier 5. Evaluate Performance Leave-One-Out X-Validation 6. Check Assumptions Synthetic Data Analysis 7. Extensions Relax assumptions
  • 9. 1. Collect Data: Multi-Modal MR Imaging • 49 senior individuals; 25 male, 24 female • diffusion: standard DTI protocol • structural: standard MPRAGE protocol
  • 10. 2. Preprocess Data: MR Connectome Automated Pipeline • coherent collection of code • fully automatic and modular • about 12 hrs/subject/core • yields 70 vertex graph/subject http://www.nitrc.org/projects/mrcap/
  • 11. 3. Data Assumptions: Signal Subgraph
  • 12. 4. Construct a Decision Rule: Robust Bayes Plugin Classifier • asymptotically optimal and robust • finite sample niceness auv 1−auv y= ˆ puv|y (1 ˆ − puv|y ) ˆ πy ˆ ˆ (u,v)∈S
  • 13. 5. Evaluate Performance: Leave-One-Out X-Validation incoherent estimator coherent estimator 0.5 misclassification rate # signal−vertices 0.5 L π ˆˆ = 0. 5 ˆ L n b = 0. 41 ˆ L c o h= 0. 16 10 0.4 0.25 20 0.3 ˆ L i n c= 0. 27 30 0 0 1 2 3 0.16 10 10 10 10 200 400 600 800 1000 log size of signal subgraph size of signal subgraph some coherent estimators zoomed in coherent estimator 0.5 lassification rate 0.5 star−vertices 15 0.4 18 0.25 0.3 0.16 21
  • 14. 6. Check Assumptions: Synthetic Data Analysis Correlation Matrix 1 100 0.5 vertex 0 200 −0.5 300 −1 100 200 300 vertex
  • 15. 7. Extensions • relax the independent edge assumption • relax binary edge assumption
  • 16. Discussion • 83% 75% • yay statistical modeling!
  • 18. 4. Construct a Decision Rule: Signal Subgraph Estimation • for each edge, we compute the significance of the difference between the two classes using Fisher’s exact test • the incoherent signal subgraph estimator finds the s edges that are most significant • the coherent signal subgraph estimator finds the s edges that are most significant incident to m vertices
  • 19. 4. Construct a Decision Rule: Signal Subgraph Estimation negative log incoherent coherent significance matrix estimate estimate # correct = 15 # correct = 7 20 vertex n=64 40 60 20 40 60 −4.4 −1. vertex
  • 20. 6. Check Assumptions: incoherent estimator coherent estimator 1 misclassification rate # star−vertices 0.75 0.7 10 0.25 0.5 Synthetic Data Analysis 20 0.5 30 0.3 0 0.18 0 1 2 3 200 400 600 800 1000 10 10 10 10 log size of signal subgraph size of signal subgraph 1 0.5 misclassification rate missed−edge rate coh 0.4 inc 0.3 nb 0.5 0.2 0.1 0 0 20 40 60 80 100 0 20 40 60 80 100 # training samples # training samples