?.????????

1
?????????? ??????

• ?.???????? ????????????? ????????
• ???? 4 ????, ????? 2007

2
???????? ?????????? ??????

• (??)-??????????
• ?????-??????? ??????????????
• ?????? ? ???????????? ??????
• ?????-???????? ??????????????
• ????????? ? ??????? ??????? (????????????????,
  ????????)
• ?????? ?????? ???????????? (text mining)
• ????? ??? ??????
• ???? ??????? ??????? ???????

3
Expression arrays (a.k.a. ????????????????? ????)

• ??????????????? (?????) ???????? ?? ????????
• ???? ?? ???? (???????????? ??? ?????????????
  ????? 2 ?????) ??????? ??? ??? ???? (????????
  ???? ????? ? ????????? ?????) ????????
  (??????????????? ????) 3-????? ?????
• ?????? ? ?????? ????? ????????????? ???
  ??????????????? ????????????

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

• ??? ????????? ?????
• ???????? ???????????
• ?? ??????? ????? ????????? (????????? ? ????
  ??????)
• ?? ?????? (????????? ?? ????? ??????)
• ???????????? (????????? ?????)
• ?????????? ???????????
• ?????????? ??????????? ?????????
• ?????????? ????????????????? ????? ???????
• ?????????? ????????? ????????? ? ???????????????
• ?????????? ????????? ????????? ? ??????
• ??? ?????????? ????????????? ? ????????????
  (?????? ???????????)
• ?????????? ????????? ? ????? ???????????? /
  ?????????? ????? ?????????????
• ???? ???????? ? ???????? ???????????? ? ?.?.
• ???? ??????????????? ?? ????
• ????????? ????
• ?????????? ?????????????? ?????????????? ?????
  (?????????)
• ?????????, ?????? ??? ?????
• ??????????? ????????????? ??????
• ?????????????? ???????????? ???????? ??????????
  ?? ?????

5
?? ? ????? ???????????????? (??? ?????
???????????, ?????????????? Toxoplasma)
6
???????????

• ??

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

• ????????
• ???-???????????? ????????? ?????
• (????? ????? ?????? ?????????? ????? ???
  ???????????? ????)
• ???? ????????? ?????????????? ?????????,
  ??????????????????, ????????? (??????)
• ? ??????????? ?? ??????? ????????????? ???????
  ????, ????? ???????????? 3-?????
• ??????????? (tiling)
• ???? ????? ?? 30 ??????????? ?? ??????? 10
  ???????????
• ?? ??????????? ????????, ??????????????? ? ?.?.

8
??????????

• ??? ?????????? ?????????????? ??????? ????, ?????
  ????????????? ???? ???????? (?????????? ??????? ?
  ?????????????????? ??????????)
• ??? ????? ??? ??????? ??????? (??????????????)
  ?????? ???????? ??????? ? ????? ??
  ?????????????????? ??????????
• ? ????????????? ????????????? ??????? ????? 0,
  ?????????????????? ?????????? ????? 1

9
???????? ??????

• ????????????? ????????? (????????, ???????????)
• ????? ?????, ??????????????? ????????????????? ?
  ???? ??????? (???????????, ??/?????)
• ????? ????? ??-???????????? ?????

10
???? ???, ????? ????????? ? ???? ???????????
??????? ???????? ?? ??????? ???????????

• ??????????? ?????? ????????? ???? ?????????????
• ??????????????? (t-????) ??????????????
  ???????????? ?????????????, ??
• ??????? ????????????,
• ????????????? ?? ?????? ?? ??????????, ?? ?????
  ???? ???????????,
• Outliers
• gt ?????-????????????? ?????????? (?????????
  ???????? ?? ??????????????)
• ????????????????? (??????????-?????-?????)
• ????????? ?????????????? ????
• gt ?????-????????????? ?????????? (?????
  ?????????? ???????? ??????)

11
bootstrapping

• ????? ?? ?? ??????, ???????????? ?????????
  ??????? ?? ??????? ???? ?? ??????, ? ????????
  ????? ?? ???? ?? ????????? ?????????????
  (????????, ????????? t-??????????)
• ?? ?????? ?? ??????? ? ??????? t-?????????????, ?
  ?????????? ??? ???????? ????? ????? ??? ?
  ???????? ????????????? ?????????? ?? ?????????
  ??????
• ? ???????, ?????? ?? ??????????

12
???? ???, ????? ??? ????????? ???? ?? ????????

• ???????? ?????? ????????? ?? ??????? ? ?????????
  ???????0?
• ?? ?? ?????, ??? ? ??????

13
????????????? ????????????

• ?????????????? ?????????? 1 ????????, ??? ?
  ????????? ?????? 1 ?? 100 ????????? (?????) ?????
  ????? ????? ????????
• ?????? ?????
• ?????????????? ?????? ???????? ??????????
  (???????? ??????? ?????????? ?? ?????????? ?????)
• ??????? ????????????? ?????? ?? ???????

14
bootstrapping

• ?????????????? ?????? ?????????, ??????? ?????
  ??????? ?????? ????? ?? p-value ? ?????????
  ?????? ???? ?? ??????
• ??? ???? ????? false positives
• ??????? ??????? ?????????? ? ?????????? ???????
  false positives
• ???????? ?????????? ????????????? 0 false
  positives

15
????????????? ??????? (??????, ????????? ? ?.?.)
????????????? ???????

• k ????????? ???????
• ?????????? ? ???????? ??????????????? ??????
  ????????? (??????, ????????) ????? ?
  ??????????? ???????????? (?????????? ??????
  ?????????? ?????) ???????? ?????????, ???????
  ????????? ??????? ????????? ???????
• ????????? ???? (?????????)
• ???????????? ??????
• support vector machines (?????? ?????????)

16
????????? ??????????? ? over-interpretation

• ????? ???????? ??????? ?????? ?????????
  (????-???????)
• ?? ??????? ?????????? ???????? ? ??????
  ?????????? ??? ???????????????? ??????? (??????,
  ???????)
• ????? ??????? ?????? ????? ?????, ??????? ????
  ????? ?? ???????? ????????

17
?????????

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

18
?????????? ????? ???????? ?????????? ?????
??????? ????????????? r 0.97
?????? ????????????? r 0.43
??????? r 0.054
19
????????? ????

• ????????? ???? (?????????????????? ????????) ???
  ??????????? ?????????????
• ????????? ??????? ?????????? ????? ?????????????
  ??????? ???????
• ????????????? ?????????? ???????? ??????????

20
????????????? ????????
21
???? ???????? ????? ????????? ????? ??????????
(?????????? ????????? ?????????????)
22
?????? ????????????? ?????????????

• ???????? ?????? (single linkage)
• ???????? ?????? (complete linkage)
• ???????????????? ?????????? (average linkage)

23
???? ???????? ??????????, ????? ?????????????
?????????????????
24
????????????? k-??????? k-means clustering

• ?????????? ????????? ???????? ???????
• ??????? ????????? ????????
• ????? ?????????
• ???????????????? ????? ??????? ????? ? ????
  ????????, ? ????????? ???????? ??? ????? ?????
• ????????? ???? ?? ????????
• ?? ?????????? ????????????? ??????? ???????
  ????????? ??? k1 ?? ???????? ? ?????????? ??????
  ?? k ????????? ?? ???

25
????????????? ??????? ??????? ?????????????
(biclustering)

• ???? ?? ???????? ?? ???????, ? ?????????
  ??????? (?? ??? ? ?? ?????? ?????????????), ?? ??
  ??????????? ?????????? ?????? ??????????? ?? ????
  ????????? ???????
• ??????? ????????????? ????????? ????? ????? ?
  ????? ???????, ?.?. ?????????? ???? ?????
  ?????????????? ? ???? ????????

26
???? ?????? ??????????? ????????????? ?? ???????
??????????

• ArrayExpress http//www.ebi.ac.uk/microarray/Array
  Express/arrayxpress.html
• Stanford Microarray Database http//genome-www5.s
  tanford.edu/MicroArray/NDEV/index.shtml
• GEO (Gene Expression Omnibus) http//www.ncbi.nlm
  .nih.gov/geo/
• ????????????????? ????? ?????? ?? ????????????
  (MIAME Minimal Iinformation About a Microarray
  Experiment)

27
GEO
28
(No Transcript)
29
???????? ?????? ?????? ???????????
????????????? ?? ????? ? ?? ????????
30
???? ??? ?????? ??????? (???????, ???????)
31
?????????

• R (GNU)
• Matlab
• Expression Profiler (EBI) http//www.ebi.ac.uk/mic
  roarray/ExpressionProfiler/ep.html

32
Expression Profiler
33
http//string.embl-heidelberg.de8080/prophecies_
html/prophecies.html
34
STRING trpB co-expression
35
(No Transcript)
36
?????????? ????????? ?????

• ????????? ?????
• ????? (?????/?????)
• ????-?????????????
• ???????
• ? ????? ??????? ????? ?????. ??? ?????? ??????
  ???? (??????! ?????? ???? ????? ??? ??????????
  ????????)

37
Pride
38
(No Transcript)
39
?????????? ???????? ????

• ????? ????????? ?? ????????, ????? ????? ????????
  ?????????? (????????, ??????????)

40
?????-???????? ??????????????

• ????????? ????-?????????????
• ????????? ???????????? ???????
• GAL4
• ??? ?????? ??????????????? (????????? ?????????)
  ? ???-???????????
• ????? ??????????? ? ??????????
• ??????????????? ? ???-??????????? ?????? ?????
  ???? ? ?????? ?????? (????? ????? ???????????
  ?????)

41
Protein-protein interactions

• MIPS, mammals http//mips.gsf.de/proj/ppi/
• MIPS, yeast http//mips.gsf.de/proj/yeast/CYGD/i
  nteraction/
• MRC, links http//www.hgmp.mrc.ac.uk/GenomeWeb/p
  rot-interaction.html
• DIP, many model organisms http//dip.doe-mbi.ucl
  a.edu/dip/Main.cgi

42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
45
(No Transcript)
46
(No Transcript)
47
(No Transcript)
48
(No Transcript)
49
STRING trpB high-throughput experiments
50
ChIP-chip (chromatin immunoprecipitation)
Briefly, cells are fixed with formaldehyde,
harvested by sonication, and DNA fragments that
are crosslinked to a protein of interest are
enriched by immunoprecipitation with a specific
antibody. After reversal of the crosslinking, the
enriched DNA is amplified and labeled with a
fluorescent dye using ligation-mediated PCR
(LM-PCR). A sample of DNA that has not been
enriched by immunoprecipitation is subjected to
LM-PCR in the presence of a different
fluorophore, and both IP-enriched and unenriched
pools of labeled DNA are hybridized to a single
DNA microarray containing all yeast intergenic
sequences.
51
(No Transcript)
52
????????

• essentiality
• 18.7 non-essential genes in yeast
• 14.4 non-essential genes in E. coli
• ? ??????? ????????
• RNAi
• synthetic lethals

53
MIPS
54
??? ??? ??????????

• ??? ??, ??? ????? ?????? ???????????

55
????????? ?????? L Huynen, Gabaldon

• COG1245 ???????????? ?? ???? ?????????? ?
  ??????
• ? ???????? RPLI1 ????????? ?????? L
  (??????????-????????? ???? ?????????? (????????)
  ???)
• ?? ?????? L ? ????? ???. ??? ?? ??? ?????? ????
  ??????

56

• ???????????????? ??????? (??????????? ?? ????
  ?????? ? ??????????, ?????????? ?? ????
  ?????????) gt 55 COG??
• ??????????, ???????? ???????, ????????????,
  ??????????, ????????????, ?????????
• ? ?????????? ???????????? ? ??????????? ???????
  ? ??????? ??????????? ????
• ? ??????? ?????-???????? ?????????????? ? HCR1
  (?????????? ????)
• ??????????? (???????????) ?????? ?????????? RLI1
  gt ?????????? ?????? ?????? ??????? ??????
• N-???????? ????? ???????? 4 ???????? ??????????
  ? ????
• ???????????? RLI1 ?????? ??????????? ????
• ??????????? ? ??????
• ??????? ?? RLI1 ????? ?????? ??????????? ???-????
• ? ??????? RLI1 ?????? ? ????????? ? ???????
  ?????? ????????????? ???????

57
??????????????? ?????? ????? ??????? Kemmeren et
al. 2005

• ?????-???????? ??????????????
• ?????????? ???????? ??????????
• ??-???????????
• ???????? ?????????

58
KRE33 killer toxin resistant, no GO annotation

• 20 ????????? ?????
• 13 ????? ????????? U3 snoRNP (?????????? ????)
• 4 ?????????? ????

59
FUN11function unknown now

• ??? 5 ??????? ????????? ??????????

60
YDR091cputative member of the ATP-binding
cassette superfamily of non-transporters

• 10 ?? 15 ??????? ????????? ??????????

61
YGR205w HSP104 (ppiexploc)

• HSP104 ????? ????????? ???? ???????
  ??????????????????. ???????.
• ???????????? HSP104 ? YGR205w ??????????? ???
  ?????? ?????
• ???????????? YGR205w ???? ????????? ? ?????? ??
  ??????
• ??????????? ??????? ?? YGR205w ????? ??????????
  ?????????????????
• ?? ?? ???????, ??????????????? ???????? ??????
  ????????

62
ASC1 (no annotation)

• 4 ???? ?????????? ????
• 6 ???????? ????????? ??????????
• Ydj1 ? ZUO1 ????? ??????, ???????????? DnaJ
  (???????, ???????? ??? ???????? ? (??????) ????),
  ZUO1 ???????, ????????? ? ?????????
• ????????????
• Ydj1 ???????
• ASC1 a role in stress-induced misfolding
• ??????????? ??????? ?? Ydj1 ? ASC1 ????? ??????
  ??? ?????????? ???????????? NaCl ? KCl

63
???? ??????? ??????? ? ???????

• ?????????? ? ???????????, ????????????? ?
  ??????????
• ??????????? ??????????????? (?????????????
  ???????) ?? ????????
• ???????? YOR271cp. ???????????
• ??????????? ? ???????????
• 4 ??????????????? ????????
• ?????????????? ???? ?????????? ???????????
  ?????????? Leu3p
• ???????????? ??????? YOR271c ????????? Leu3p ?
  ChIP-chip ???????????? (????????????? ?
  ???????????????? ???????????? ???????? ?? 50,
  ?????? ?????????? ? ??????????????? ??????? ???)
• ??????????? ???????????? ???????????????? ?????
  (???? ??????????? ??? ????????? ???????? ??????
  ????????? ??????? ?????????????, ?????,
  ??????????? ? ?????????? ??????)

64
(No Transcript)