Inference of Transcriptional Regulation Relationships from Gene

Inference of Transcriptional Regulation Relationships
from Gene Expression Data
Andrew T. Kwon
Holger H. Hoos
Dept. of Computer Science
University of British Columbia
Vancouver, BC, Canada
Dept. of Computer Science
University of British Columbia
Vancouver, BC, Canada
[email protected]
[email protected]
[email protected]
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ABSTRACT
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Categories and Subject Descriptors
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INTRODUCTION
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1.
Permission to make digital or hard copies of all or part of this work for
personal or classroom use is granted without fee provided that copies are
not made or distributed for profit or commercial advantage, and that copies
bear this notice and the full citation on the first page. To copy otherwise, to
republish, to post on servers or to redistribute to lists, requires prior specific
permission and/or a fee.
SAC 2003, Melbourne, Florida, USA © 2003 ACM 1-58113-624-2/03/03
... 5.00.
‘
Raymond Ng
Dept. of Computer Science
University of British Columbia
Vancouver, BC, Canada
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2. PRIOR WORK
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THE EVENT METHOD
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1
0.5
Expression: ln(R/G)
0
-0.5
-1
-1.5
-2
-2.5
-3
0
2
4
6
8
10
12
14
16
18
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time
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4. EXPERIMENTAL RESULTS
1
Expression: ln(R/G)
0.5
0
-0.5
-1
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-2
0
2
4
6
8
10
12
14
16
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70
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edge
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event
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number of true positives
number of true positives
70
50
40
30
20
60
50
40
30
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10
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1000
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7. REFERENCES