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Temporal Analysis of Platelet Data in Chronic Viral Hepatitis Dataset. Shoji HiranoShusaku Tsumoto hirano@ieee.orgtsumoto@computer.org Department of Medical Informatics, Shimane University, School of Medicine, Japan. Outline. Introduction - PowerPoint PPT Presentation
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Temporal Analysis of Platelet Data in Chronic Viral Hepatitis Dataset
Shoji Hirano Shusaku Tsumotohirano@ieee.org tsumoto@computer.org
Department of Medical Informatics, Shimane University, School of Medicine, Japan
Outline
Introduction Cluster analysis system for time-series medical data Experimental results
1. Cluster analysis of platelet (PLT) sequences
2. PLT-based analysis of the progress speed of liver fibrosis
Conclusion & Future Work
Introduction
Platelet (PLT) decrease in chronic viral hepatitis The liver plays an important role in generating platelets Bleeding is often observed on the patients at the terminal stage of l
iver cirrhosis Liver fibrosis -> dysfunction -> PLT decrease -> bleeding
Use of PLT count as an noninvasive index for evaluating liver fibrosis [F0 (no fibrosis), F1, F2, F3, F4 (liver cirrhosis)] PLT counts correlate with fibrotic stage (Matsuura et al., J. Viral He
pat. 2000), according to PLT counts at the time of biopsy
However, Time-series analysis of the PLT data have rarely been performed Features of temporal patterns/courses have not been examined
Introduction (cont’d)
Difficulties in time series comparison Irregular sampling intervals, irregular sequence length Existence of events with different length and phase
Difficult to find the corresponding pairs of pointsbe compared
3-6M 4 years1-2 Weeks
IFN 6m
9 years
Cluster Analysis System
4 years1-2 weeks
PLT
IFN 6 m
9 years
IFN 6 m
Seq 1 Seq 2
Global
Local
Sc
ale
Similar
Match
Structural Dissimilarities
Time-series Medical Data
Multiscale Comparison
Cluster representation of time seriesGrouping
Experiment 1: Cluster Analysis of PLT Sequences Objective
Discovery of common temporal courses in platelet sequences Discovery of relations between platelet courses and fibrotic stages
Used data Chronic hepatitis dataset provided by Chiba University Total 488 cases
(Type B: 193, Type C w/o IFN: 99, Type C with IFN: 196) (Male 343, Female 145 (145:48, 61:38, 137:59))
Procedure Generate a dissimilarity matrix using the modified multi-scale matchin
g Generate a dendrogram from the matrix using agglomerative hierarchi
cal clustering (average linkage) and perform cluster analysis
Experiment 1
Cluster Constitution w.r.t. Fibrotic Stages
Type C, IFN (total 196 cases)
F0 F1 F2 F3 F44 0 3 1 0 0 45 0 2 1 2 6 116 0 1 0 1 1 38 0 9 6 9 16 409 0 3 0 0 0 310 0 1 0 1 3 511 2 24 8 9 3 4612 1 22 10 6 3 4220 0 4 1 0 0 522 0 2 0 0 1 323 1 13 4 1 0 19
Number of Cases / Fibrosis StageCLUSTER Total N
※ clusters of N < 3 omitted
F4 Major
F1 Major
Experiment 1
Grouped Sequences
F4, F3 major clusters (Type C, IFN)Cluster 5: N=11 (0/2/1/2/6)
Normal H (350 x10^3 /ul)Normal L (120 x10^3 /ul)
Cluster 8: N=40 (0/9/6/9/16)
※first 16 cases
0 5 10 15Y
Number of cases (F0/F1/F2/F3/F4)
Male 10, Female 1 Male 27, Female 13
Experiment 1
Grouped Sequences
F1, F2 major clusters (Type C, IFN)Cluster 11: N=46 (2/24/9/9/3) Cluster 12: N=42 (1/22/10/6/3)
※First 16 cases0 5 10 15YMale 34, Female 12 Male 32, Female 10
Experiment 1
Grouped Sequences
Clusters containing remarkable increase/decrease cases
Cluster 4: N=4 (0/3/1/0/0)
Cluster 6: N=3 (0/1/0/1/1)
Cluster 10: N=5 (0/1/0/1/3)
0 5 10 15Y
Male 2, Female 2
Male 2, Female 1
Male 4, Female 1
Experiment 1
Relationships between PLT and GPT
F4, F3 major clusters (Type C, IFN)Cluster 5: N=11 (0/2/1/2/6)
Normal H (350 x10^3 /ul)Normal L (120 x10^3 /ul)
0 5 10 15Y
Normal H (40 IU/L)Normal L (7 IU/L)
0 5 10 15Y
PLTPLT GPTGPT
Experiment 1
Relationships between PLT and GPT
F1, F2 major clusters (Type C, IFN)Cluster 11: N=46 (2/24/9/9/3)
0 5 10 15Y
PLTPLT GPTGPT
※First 16 cases※First 16 cases
Experiment 1
Relationships between PLT and GPT
Clusters containing remarkable increase/decrease cases
Cluster 4: N=4 (0/3/1/0/0)
Cluster 6: N=3 (0/1/0/1/1)
Cluster 10: N=5 (0/1/0/1/3)
0 5 10 15Y
PLTPLT
GPTGPT
GPTGPT
PLTPLT
GPTGPT
PLTPLT
Experiment 1
Summary
Fibrotic stage and PLT course F4/F3 major clusters
Lower PLT level, below the normal range Decreasing, or flat courses Some F1/F2 cases may follow similar courses
(ex. Type C IFN cluster 5) F1/F2 major clusters
Moderate PLT level within the normal range (ex. Type C with IFN clusters 11, 12, 23)
Mildly decreasing, or flat courses PLT level may correspond to fibrotic stages (ex. Type C with IFN clusters 23 > 12 > 11 )
Experiment 1
Summary
Fibrotic stage and PLT course Fast increase/decrease cases
Some cases rapidly descent from normal range regardless of fibrotic stage (Type C with IFN clusters 4,6)
Some cases rapidly ascent toward normal range (after IFN therapy)(Type C with IFN cluster 10)
Relationships between PLT and GPT Chronically high GPT level may induce the descent of
PLT, progressing the fibrotic stage Difficult interpretation of GPT patterns; high level
followed by flat low level Cured cases or terminal cases ?
Experiment 2: PLT-based Analysis of Progress Speed of Liver Fibrosis
Assumption: Diminishing PLT (below the normal low limit; NL) for long time -> F4 stage
Using PLT-based stage estimation and biopsy information, we analyzed Years for reaching F4 stage Years elapsed between stages
1Y
Normal Low (NL)
Normal High (NH)
PLT diminishing below the NL
MID 466
(7.92Y)
F4(PLT)F1(biopsy)
Experiment 2
Preprocess: Sequence Selection
Excluded sequences 1. No biopsy information 2. Short: # of exam < 3, or duration of exam < 2Y 3. Inhomogeneous: SD of exam intervals > 1Y
Interval 14 Y
Inhomogeneous seq.
Interval 1M
MID 215
Normal Low (NL)
Normal High (NH)
Experiment 2
Preprocess: Sequence Smoothing
Removal of short-term changes Convolution with Gaussian kernel with 6M width(=2.8)
Experiment 2
Discrimination of Diminishing Cases
Criteria 1. Keeps diminished PLT counts (below the normal level)
at least for 6 month 2. Once diminished, never maintain normal PLT level for
6 month at any time until the last examination
1Y 6 M
Diminished Case
MID 466
Normal Low (NL)
Normal High (NH)
Experiment 2
Discrimination of Diminished Cases
Criteria 1. Keeps diminished PLT count (below the normal level)
at least for 6 month 2. Once diminished, never maintain normal PLT level for
6 month at any time until the last examination
6 M
Not Diminished Case
6 M
Recovery
MID 37
Normal Low (NL)
Normal High (NH)
Experiment 2
Selection Results
PLT data exist, but no biopsy information available
# of exam < 3, or Duration of exam < 2Y
SD of exam interval > 1Y
Not diminished below NL
Excluded fromAnalysis
Subject forAnalysis
Selection Results (Total 720 Cases)
Numbers in (): ratio (%)
NotDiminishing Diminishing
222(30.8) 82(11.4) 28(3.9) 291(40.4) 97(13.5) 720
TotalSubject for DiscreminationNo biopsy
Info Short Inhomo-geneous
Experiment 2Years for Reaching F4: Two Measures
First-exam basis: Years from the first PLT examination First-biopsy basis : Years from the first biopsy
Fibrotic stage at starting date: stage observed at the first biopsy Years = 0 if the date for diminishment is earlier than the first biopsy
Diminished date (below NL)
F4 (PLT)First biopsyF1 (biopsy)
First PLT examF1 (stage at first biopsy)
First-exam basis
First-biopsy basis
MID 216
Normal Low (NL)
Normal High (NH)
Experiment 2Years for Reaching F4: Summary for 97 Diminishing Cases (First-exam basis)
Mean Median SDB 1 5 2.36 0.00 3.53 3
2 9 5.04 1.79 6.29 23 8 2.44 0.66 3.62 34 9 1.43 0.00 2.56 5
B subtotal 31 2.89 0.56 4.38 13C with IFN 0 1 13.08 13.08 - 0
1 8 4.05 3.87 3.15 22 6 3.89 3.70 3.90 23 10 2.26 2.30 2.43 44 15 1.84 0.00 3.02 8
40 2.98 2.32 3.46 16C w/ o IFN 1 7 4.29 4.50 3.52 2
2 2 4.05 4.05 5.72 13 5 2.49 0.12 3.64 24 12 2.21 0.00 3.15 7
26 2.97 0.65 3.42 12Total 97 2.95 1.19 3.73 41
C with IFN subtotal
C w/ o IFN subtotal
Type Years=0cases
Years for reaching F4 (First-exam basis)(Y)Stage Cases
Experiment 2Years for Reaching F4: Summary for 97 Diminishing Cases (First-biopsy Basis)
Mean Median SDB 1 5 3.70 3.71 3.46 1
2 9 4.26 2.85 5.45 33 8 2.12 0.22 3.72 34 9 1.31 0.00 2.54 5
B subtotal 31 2.77 0.52 4.00 12C with IFN 0 1 13.08 13.08 - 0
1 8 2.44 2.38 2.36 22 6 2.54 0.83 3.42 33 10 1.99 2.14 2.05 34 15 2.01 0.00 3.51 9
40 2.44 1.18 3.30 17C w/ o IFN 1 7 1.47 1.17 1.76 3
2 2 3.70 3.70 5.24 13 5 2.27 0.00 3.54 34 12 0.26 0.00 0.54 9
26 1.23 0.00 2.27 16Total 97 2.22 0.44 3.34 45
C with IFN subtotal
C w/ o IFN subtotal
Years for reaching F4 (First-biopsy basis)(Y) Years=0casesType Stage Cases
Experiment 2Years Elapsed between Stages: Summary for 97 Diminishing Cases (First-biopsy Basis)
Mean Median SDB 1 5 1.23 1.24 1.51
2 9 2.13 1.42 2.733 8 2.12 0.22 3.724 9 - - -
B subtotal 31 1.92 0.62 2.80C with IFN 0 1 3.27 3.27 -
1 8 0.81 0.79 0.792 6 1.27 0.41 1.713 10 1.99 2.14 2.054 15 - - -
40 1.49 1.07 1.66C w/ o IFN 1 7 0.49 0.39 0.58
2 2 1.85 1.85 2.623 5 2.27 0.00 3.544 12 - - -
26 1.32 0.20 2.30Total 97 1.60 0.80 2.25
C with IFN subtotal
C w/ o IFN subtotal
Years between stages (Y/ stage)Type Stage Cases
Experiment 2
Summary
PLT-based estimation about years for reaching F4 and years elapsed between stages Assumption: Diminishing PLT (below NL) over long time
-> F4 stage Keeps diminished PLT below NL at least for 6 month Cannot maintain normal PLT level over 6 month at any time from t
he time it diminished below NL to the last examination Analyzed a total of 97 diminished cases
(31 Type B, 40 Type C with IFN, 26 Type C w/o IFN cases)
Years for F4: 2.95 Y (av. 97 cases, first-exam basis) 2.22 Y (av. 97 cases, first-biopsy basis)
Years between stages: 1.60 Y/stage ( av. 97 cases, first-biopsy basis)
Conclusion
Presented the results of temporal analysis of platelet data in chronic viral hepatitis dataset
Findings: Temporal courses of PLT might be classified into some patterns acc
ording to their levels and trends which might be further related to fibrotic stages.
In some exacerbating cases, liver fibrosis may proceed a few times faster than the natural courses.
Further validation of the clinical reasonability of the results Application of the analysis scheme on other items/dataset
s.
Future Work
Cluster Constitution w.r.t. Fibrotic Stages
Type C w/o IFN (total 99 cases)
F0 F1 F2 F3 F41 0 4 4 5 9 222 0 1 0 1 1 33 1 27 6 7 6 474 0 1 0 0 0 15 0 11 2 0 0 136 2 11 0 0 0 13
CLUSTER Number of Cases / Fibrosis Stage Total N
Grouped Sequences
F4, F3 Major Clusters (Type C, w/o IFN)Cluster 3: N=47 (1/27/6/7/6)
※First 16 cases
Cluster 1: N=22 (0/4/4/5/9)
※First 16 cases0 5 10 15YMale 14, Female 8 Male 27, Female 20
Relationships between PLT and GPT
F4, F3 major clusters (Type C, w/o IFN)Cluster 1: N=22 (0/4/4/5/9)
※First 16 cases0 5 10 15Y
PLTPLT GPTGPT
※First 16 cases
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