Gene Expression

1
Gene Expression Transcription Regulation

• Dafna Arad
• Noa Gordon
• 20/5/02

2
????

• ????? ????? ?"? ?????? ????? Transcription
  Factors (TFs) ??????? ????? ???? Regulatory
  Motifs ????? ????????? ?? ???.

3

• ?????? ???????????, ??? ???? ?????? ????? ?????,
  ??????????? ????? ?????? ?????? ?????????? ??
  ??????? ?????????
• ??? ????? ????? ???? ?cis ?/?? ? trans
• ???? ????? ????? ?? ???? ?? ?????/????? ?????
  ????? ???? ?? on/off
• ???? ????? ????? ???? ?????? ?????? ?? ?????
  ????????
• ?????? ?????? ?????? ? DNA , ?- RNA Pol ????
  ???? ??????? ??????? ?????? ?????.

4
???? ????? ?? ????? ????? ?????? ?????? ??????
??????

• ???? ???? ???? ???? ?????? ?????? ?????
• ??? ????? ?? ?????? ????? ???? ?? ???? ???? ?????
• ??? ???? ????? ?????? ????? ?? ?? ??? ???? ?????
  ????
• ??? ???? ??????? ??? ?????? ????? ????? ????
  ????? ???????

5
Bucher P.Regulatory elements and expression
profilesCurr Opin Struct Biol 9 400-407??????

• ????? ?????? ?????? ??-????? ????? ?????? ???????
  ????? ?????.
• ??? ???? ????? ????? ????? ???? ????? ??? ????
  ??????? ???? ????? ????? ???? ????.

6
??????

• ??????? ???? ??????? ????? ?????? ?? ???? ?????
  ???? ????? ?"? ??????????? ?? ??????? ??????
  ??????? ?????? ?????? ???? ???? ????? ????? ????
  ????? ?? ??? ????? ????? ??????. ?????, ??? ??
  ??? ????? ?????? ??? ?????.

7
????? ?????? ????? ???? ??? ????

• Bottom up ??????? ????? ???? ???? ?????? ?????
  ?????? ????????????? ?????? ??? ?????? ??? ?????
  ???????????? (???? ????)
• ???? ????? ?? ???????????? (????? ????????)
• Top down ??????? ?????? ?? ????? ???? ?? ????
  ???????? ??? ?????? ????? ???? ???? ????. (?????
  ????? ???????? ???, ??????? ???)

8
Church GM Computational Identification of
Cis-regulatory Elements Associated with
Groups of Functionally Related Genes in
Saccharomyces cerevisiae J. Mol Biol 296 1205-1214

• ???????? ?????? ???????
• AlignACE(Align nucleic Acid Conserved
  Elements)
• ????? ?? Gibbs Sampling algorithm

9
AlignACE

• ???????????? ????? ????????? ??
• ???? ????? ????? ????? ????? ??? ?????? ?????
  ??????????? ????? ?????.
• ????? ????? ???? ???????. ????? ????? ?????.
• ????? ???? ???????. ???? ????? ?????? ?? ??????
  ?? ?? ?? ??????? ??????.

10
AlignACE

• ???? ????? ??????? ?????, ?? ???? ?????? ?? ????
  ???????? ??? Regulon.
• ????? ?????? ?????? ????
• ???? ?? ????? RNA - Clustering
• ??????? ???????? ?????????

11
AlignACE Example
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
300-600 bp of upstream sequence per gene are
searched in Saccharomyces cerevisiae.
12
?????? ?????
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
HIS7
ARO4
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
ILV6
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
ARO1
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
HOM2
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
PRO3
AAAAGAGTCA
AAATGACTCA
AAGTGAGTCA
AAAAGAGTCA
GGATGAGTCA
AAATGAGTCA
GAATGAGTCA
AAAAGAGTCA
MAP score 20.37 (maximum)

13
?????
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
HIS7
ARO4
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
ILV6
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
ARO1
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
HOM2
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
PRO3
TGAAAAATTC
TGAAAAATTC
GACATCGAAA
GACATCGAAA
GCACTTCGGC
GCACTTCGGC
GAGTCATTAC
GAGTCATTAC
GTAAATTGTC
GTAAATTGTC
CCACAGTCCG
CCACAGTCCG
TGTGAAGCAC
TGTGAAGCAC
MAP score -10.0


14
sampling
Add?
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
HIS7
ARO4
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
ILV6
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
ARO1
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
HOM2
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
PRO3
TCTCTCTCCA
TGAAAAATTC
TGAAAAATTC
?? ????? ????? ??? 2 ?- ?alignments
GACATCGAAA
GACATCGAAA
GCACTTCGGC
GCACTTCGGC
GAGTCATTAC
GAGTCATTAC
GTAAATTGTC
GTAAATTGTC
CCACAGTCCG
CCACAGTCCG
TGTGAAGCAC
TGTGAAGCAC


15
Add?
Remove.
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
HIS7
ARO4
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
ILV6
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
ARO1
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
HOM2
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
PRO3
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
ATGAAAAAAT
TGAAAAATTC
TGAAAAATTC
?? ????? ????? ??? 2 ?- ?alignments
GACATCGAAA
GACATCGAAA
GCACTTCGGC
GCACTTCGGC
GAGTCATTAC
GAGTCATTAC
GTAAATTGTC
GTAAATTGTC
CCACAGTCCG
CCACAGTCCG
TGTGAAGCAC
TGTGAAGCAC


16
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
HIS7
ARO4
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
ILV6
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
ARO1
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
HOM2
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
PRO3
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
?? ????? ????? ??? 2 ?- ?alignments
GACATCGAAA
GACATCGAAAC
GCACTTCGGC
GCACTTCGGCG
GAGTCATTAC
GAGTCATTACA
GTAAATTGTC
GTAAATTGTCA
CCACAGTCCG
CCACAGTCCGC
TGTGAAGCAC
TGTGAAGCACA


17
?????? ?????
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAGAGTCAGACATCGAAACATACAT
HIS7
ARO4
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATGACTCAACG
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
ILV6
5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
ARO1
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTCATCCCGAACATGAAA
5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
HOM2
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTC
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
PRO3
AAAAGAGTCA
AAATGACTCA
AAGTGAGTCA
AAAAGAGTCA
GGATGAGTCA
AAATGAGTCA
GAATGAGTCA
AAAAGAGTCA
MAP score 20.37 (maximum)

18
masking
5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTC
ATGAGAAAAXAGTCAGACATCGAAACATACAT
HIS7
5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTG
CATTTTGTACGTTACTGCGAAATXACTCAACG
ARO4
5- CACATCCAACGAATCACCTCACCGTTATCGTGACTXACTTTCTTTC
GCATCGCCGAAGTGCCATAAAAAATATTTTTT
ILV6
5- TGCGAACAAAAXAGTCATTACAACGAGGAAATAGAAGAAAATGAAA
AATTTTCGACAAAATGTATAGTCATTTCTATC
THR4
5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAAT
TGTCATGCATATGACTXATCCCGAACATGAAA
ARO1
5- ATTGATTGACTXATTTTCCTCTGACTACTACCAGTTCAAAATGTTA
GAGAAAAATAGAAAAGCAGAAAAAATAAATAA
HOM2
5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTXATTCTGACTX
TTTTTTGGAAAGTGTGGCATGTGCTTCACACA
PRO3

• ?? ?? ????? ????? ????? ??????.
• ??? ?? ????? ??? ??? ??????? ??????? ?? ??????.
• ???? ???? sampling ?? ???? ????? ??????? ???? ??
  ?? ?????.

AAAAGAGTCA
AAATGACTCA
AAGTGAGTCA
AAAAGAGTCA
GGATGAGTCA
AAATGAGTCA
GAATGAGTCA
AAAAGAGTCA

19
MAP ScoreMaximum a priori log likelihood

• ?????? ???? ?? ??? ????? ???? ?? ????? ???? ????
  ????????? ????? ??????? ?????.
• MAP Score N log R
• ????
• N - ???? ???? ????? ???????.
• R - ??? ????? ???? ?? ?????? ?????? ???????,
  ????
• ?? ??? ????? ?? ?????? ???? ?????? ??? ?-1000
  ??????
• ??? ?????? ???????????? ?????, ?????? 10 ?????
  ??????? ?? ?????? ?-2000 ?????? ?? 5R.

20
MAP Score

• ??????? ????? ????? ????? MAP Score ???? ????
• N ??? ???? (???? ???? ???? ??????)
• ???? ???? ???? ?? ????? ??????? ?? ??????.
• ??????? ?????? ????.
• ?????? ??????? ?? ?????? ????????? ????
• ?????? ??????? ?? ?????? ?????? ??????????? ?????
  ?????? ?????.

21
????? ????? AlignACE ????

• ????? ?? ????????? ?? ?????? ???? ?????
• 248 ?????? ???? ??????? ?????.
• ?????? ?????? 29 ?????? ????? ??????.
• ?????? ?????? ?????? ? false positive
  ?????? ????????? ?????? ????? ?? ORFs

22
????? ????? AlignACE ???? (??????)

• ?????? 3311 ???????.
• ??? ???? ?? ????? ???????? ???? ??? ????? ??????
• Group specificity
• Positional bias

23
Group Specificity Score

• ?????? ?????? ?? MAP Score ??? ?????? ???????? ??
  ????????? ?????? ????? ????, ???? ??? ??????
  ??????? ????? ?????. ???? A-rich motifs ????.
• Group Specificity Score ???? ?????? ?? ?? ?????
  ?????? ????? (?"?ScanACE ). ???? ???? ?????
  ?????? ??????? ??????? ????? ?????, ????? ????.

24
ScanACE

• ???? ?????? ?????? ?? ?? ??????? ?? ????? ?????
  ????? ????.
• ??? ?????? ????? ????? ??? ??? ?? AlignACE .
• ??????? ?????? ?? ????? ???????, ????? ?????
  ???????? ????? .

25
Positional Bias

• ????? ????? ?? ?????? ???????? ????? ?????? ?????
  ???? (???? ScanACE) ?????? ?? ?????? ????? ????
  ????? ?????? ????? ?????.
• ?????? ???? ???? ???? ???????? ??????? ???? ?????
  ????? ?????? ?????.

26
Clustering

• ??? ???? ??????? ???? ?????? ??????? CompareACE.
• ??????? ????? clustering ??? ??????? ???????
  ?????? ????? 6 ????? ????????????? ?? ?? ?????.
• ????? ?? ??? 1 ?- 1- ?????? ?-1 ???? ?? ?????
  ?????? ??? ??? ???????.

27
????? ????? AlignACE ???? (??????)
28
????? ????? AlignACE ???? (??????)

• ???? ????? ???? ?? ????????, ?- clustering??????
  54 ???????, ?????? ?-25 ??????.
• ??????? ?????? ???? ?????? ???????? ?????? ?"?
  AlignACE ???? ????? ???? ?? ??? ?????? ??????.
• ??????? ?? ?????? ???? ??????? ??? ??? ??????
  ?????? ?????.
• ???? ????? S12 ?????? ????? RRPE - ????
  ????? ???? ?????? ????? positional bias ???.
  ?????? ???? ????? ??????? ?????? rRMA.

29
????? ????? AlignACE ???? (?????)

• ?????? ?????? ???? 29 ??????? ?????? ???? ????
  ?-5 ???? ?????, ????? 21.
• ????? ?- false negative ??? 28.
• ?????? ?????? - 250 ?????? ?????? ????? ?? ORFs
  ?????.
• ??????? ??? ?????? ??? ????? ?? ????? ?- false
  positive ??? ?????? ????????.

30
????? ??????

• ????? ?? ???????? AlignACE ?????? ????? ??????
  ???? ????.
• ???? ????? ????? ????? ???? ??????????? ??? ????
  ??????, ????? ??? ?????? ??? ??? ?????? ?????? ??
  ???? ?????? ?????.
• ???? ????? ???? ?????? ??????? ????? ??????? ??
  ????? ????? ???. ?? ???? ??? ?????? ?? ?? ??????
  ??? ????? ?????? ???, ?????? ?????.

31
?????
32
????? ??????

• ????? ?? ???????? AlignACE ?????? ????? ??????
  ???? ????.
• ???? ????? ????? ????? ???? ??????????? ??? ????
  ??????, ????? ??? ?????? ??? ??? ?????? ?????? ??
  ???? ?????? ?????.
• ???? ????? ???? ?????? ??????? ????? ??????? ??
  ????? ????? ???. ?? ???? ??? ?????? ?? ?? ??????
  ??? ????? ?????? ???, ?????? ?????.

33
Pilpel Y. Identifying regulatory networks by
combinatorial analysis of promoter elements
Nature genetics 29 153-159

• ????? ???? ???? ?????? ?? ???? ??? ??? ????
  ???? ???????, ?????? ?? ?????? ?? ?????? ??????.
• ?????, ???? ???? ?????? ?? ??????? ?????????
  ?????? ?? ??????? ??????? ? ScanACE ?????? ??
  ????? ????? ??? ?????? ??????? ????? ???
  ????????? ????.

34
Expression Coherence

• ??? ?????? ?? ????? ?? ????? ?? ????? ?????, ???
  ????? ???? ????? expression coherence ??????
  ?????. ((EC
• ?????? ??? ??? ?????? ????? ?? ????? ?????? ??
  ?? ????? ?????? ?? ??????.

35
(No Transcript)
36
Expression coherence
37
Synergistics

• ???, ???? ?? ??? ??????? ????? ?? ?? ??????
  ?????? ?????, ?????? ???????.
• Synergistic motifs ?? ??? ??????? ??????
  ??????? ???? ????????? ????? EC ???? ???? ???????
  ??? ???? ??????? ???.
• ??? ????? ???????? ???????? ???? ????? (0/1)

38
(No Transcript)
39
Synergistics

• ???? ?????? ??????? ????? ?????, ??????? ???????
  ?? ???? ?? ????? ?????? ??????.
• ??????? ???? ?????? ?? ???? ?? ????? ??????????
  ?? microarray data ??????? ????? ????? ??
  clustering ??? ????? ??????????? ?????? ???????.

40
????? ?????????

• ?????? ?????? ????? ???????, ???? ???? ??????
  ?????? ?????? ???? ????????? ???????????? ???.
• ????? ????? ????? ?????? ?????????
• ????? ??? 2 ???????? ???? ????? ????? ????.
• ???? ?? ??? ???????, ??? ??? ???? ????? ????
  ???? ????? ????? ?????? ???? ????.
• ????? ????? ????? ?????? ???????? ??????? ???????.

41
?????
42
(No Transcript)
43
Global motif synergy map

• ??? ?????? ???????????? ???? ???? ???? ??? ?????
  ????? ?? ??????? ????? ?????, ????? ??? ???????
  ?????? ?? ?????? ????????????? ??? ??????? ??????
  ????? ??.

44
Global motif synergy map
45
Global motif synergy map

• ???? ??? ?? ?????? ????? ?????? ??????? ?????
  ??????? ????? ?? ????? ?????? ????? ?????? ?????.
• ???? ??????? ???????? ???? ????? ?? ????? ??????
  ????.
• ??????? ??????? ??????? ????? ????? ??"? ???????
  ???.

46
???? ??? ???????? ??????? ?????

• ?????? ????? ??????? ???? ???? ?? ????? ?? ?????
  ?? ????? ??????
• ???? ??? ??????? ??????, ??? ????? ??? ????? ????
  ?????? ?????? ?? ?????? ?????? ????? ?????
• ???? ?????? ??????? ???? ??? ??????? ???????
  ?????? ?????? ????? ?????? ???? ????? ??? ??
  ???????? ???????? ?????? ?????? ?????? ??????.
• ???? ?? ????? ??? ????? ??? ????? ?/?? ?????
  ?????? ??????.

47
Combinogram

• ??? ????? ?? ???? ???????? ?????? ?????? ??????
  ??? ??????? ????????? ???????? ?????.
• ???? ????? ?? ?????? ?? N ??????? ?? ????? ????
  ??????? ???? ??????? ????? ?????? ??????? ???.

48
GMC

• ?? ?? ????? ???? "????? ???????" ????? ?? 1-??
  ?-0-?? ????? N ?????? ?? ??????/???? ?? ?? ???
  ?-N ???????? ????????? ???.
• ?? ????? ???? ???? ????? ??????? ?????? ????
  ??????? ?? ??? ????? ????????.
• GMC - gene motif combination
• ?????? ?? ?- EC ???? ?? GMC.

49
GMC
50
Dendogram

• ???? ?????? ????? ????? ??? GMC .
• ???? clustering- ????? ??????? ?? ??? ????? ???
  ??????? ?????.
• ???? ?? ?????? ?- clustering ?- Dendogram.

51
(No Transcript)
52
(No Transcript)
53
??????- Cell Cycle Sporulation

• ???? ?- MCB ??? ???? ????? ?????? ?????? ??????
  ?? 1G.
• ??? ?????? ?????? ?????? ??? ?- GMCs ??????
  ?????? ?? 1G.
• ?- GMC ????? ?? ?? MCB ??? ??? ?????? ??.
• ?????, ????? regulatory cross-talk ??? ???
  ????????

54
?????

• ??????? ????? ??????, ?????? ??????? ?????
  ??????, ?????? ????? ?"? ????? ????? DNA ??
  ??????? ????? ???? ??? ?? ???? ?????.
• ????? ??? ???? ???????? ?????? ????? ???? ??? ??
  ???? ??????
• AlignACE ????? ??????? ?????? ?????? ?????.
• Synergy map ????? ?????? ???? ?????? ??? ??????
  ????? ?????, ???????? ????? ?????.
• Combinogram Analysis ????? ????? ?????? ???
  ??????? ???????? ?????.

55
?????

• ?? ??? ?? ????? ??? ?????? ??????
• ???? ?????? ????? ?????? ???? ??????.
• ????? ?????? ??? ?????? ????? ???? ??????? ???.
• ??? ??? ??? ??????, ?????? ????? ???????? ??????
  ????? ???? ?"? ???????.

56
??? ?????? ???!