??????-??????? ?????

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

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

????????????? ????? ??????????????, ????????,
?????????? ????-???, ?????????, ?????? 2006
2
?????? ??????

• GOLD361 ?????? ?????? ???????? 952
  ???????? 58 ????? 607 ???????? (? ?.?. EST) 46
  ???????????

3
46 ???????????

• complete
• Sargasso Sea 1600 ??
• Methane-oxidizing archaea from deep sea sediments
  111 ??
• Minnesota Soil 100 ??
• Acid mine drainage (AMD) 75 ??
• Woolly mammoth 28 ??
• Whale falls 25 ??
• Antarctic Marine Bacterioplankton 12 ??
• Pleistocene Cave Bears 1 ??
• DOE Hanford Site
• incomplete, ?? ? ??????? ??????? ???
  ?????????????
• Hawaii Ocean Times Series Station (HOT) 2000 ??
• Rice endophyte community 100 ??
• Poplar endophytic bacteria 37 ??
• Alaskan Soil 8 ??
• Pacific Beach Sand 3 ??
• Calyptogena magnifica symbiont 1.2 ??
• Biofilms in drinking-water networks

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

• Escherichia 532 Shigella 65
• Salmonella 518
• Staphylococcus 179 (aureus 95)
• Streptococcus 1735
• S. pyogenes 77
• S. pneumoniae 77
• Bacillus anthraciscereusthuringiensis 722
• Mycoplasma 1216
• Chlamydia 45 Chlamydophyla 62

5
???????? ?????????? ??????

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

6
?????? ?? ????????? ???????

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

7
???? ????? (expression arrays)

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

8
???????? ??????

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

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

• 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)

10
???????? ?????? ?????? ???????????
????????????? ?? ????? ? ?? ????????
11
Plasmodium ???? ???????? ? ?????????? Bozdech
et al., 2003
12
?????-???????? ??????????????

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

13
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.
14
(No Transcript)
15
??? ????? ??????

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

16
Haemophilus influenzae, 1995
17
Vibrio cholerae, 2000
18
??????????????? ?????? ????? ??????? Kemmeren et
al. 2005

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

19
KRE33 killer toxin resistant, no GO annotation

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

20
ASC1 (no annotation)

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

21
Metabolic pathways
22
STRING server (EMBL Bork)- positional
clustering- fusions- phyletic patterns-
co-expression- high-throughput experiments -
text mining (Medline abstracts)- databases
23
Functionally dependent genes tend to cluster on
chromosomes in many different organisms
24
More genomes (stronger links) gt highly
significant clustering
25
???????? ? ???????? ????? (??????)
26
????????????? ??????? ?????(??????????? ???
????????????, ?????????? ??? ??????????)
27
????????? ????????????? ???????????

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

28
???? ??????? ????????????? ?????? ? ???
??????????? ? ????? ?????? ????????????? ????????
29
?????????? ?????????????? ??????????? ? ????????
????????.

• ???????????? ???? ????? ? ?????????? ??????
  ???????? ?????? ?????? ????????? ????????????
  ?? one-carbon metabolism (????????)

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

• N ?????????? ??????
• ????????????? ???????? ?????? P(k) ???????????
  ????, ??? ? ???????? ?????? ??????? ????? k ?????
• ??????? ????? ???? ????? ????????? L
• ??????????? ????????????? ???? ????? ?????
  ???????? ?????? ???????

31
????????? ????

• ????????????? ????????????? P(k) exp(-?) ?k /
  k!
• ??????? ??????-????? ??????? ???????
  ????????????? ?????????? ??????????
• ??????? ????? ???? log N

32
scale-free network

• P(k) k?
• ?gt3 ?????? ??????????
• 2lt?lt3 hubs, ????????
• ?2 ??????? hub, ??????????? ? ??????? ?????
  ??????
• ??? ?lt3 ???????? ????????? ??????? ?? ?????????
  ????, ???????? hub? ?????????
• ??????? ????? ???? (??? 2lt?lt3) log log N

33
?????? ???? ??????

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

L.Barabasi
34
Yeast protein interaction network

• Data from the high-throughput two-hybrid
  experiment (T. Ito, et al. PNAS (2001) )
• The full set containing 4549 interactions among
  3278 yeast proteins
• 87 nodes in the largest component
• The highest connected protein interacts with 285
  others!
• Figure shows only nuclear proteins

Sergei Maslovs web site
35
(No Transcript)
36
?????????? ?????????? ? ????? ?????-????????
?????????????? ? ???????

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

37
?????-???????? ?????????????? ? ??????? P(k) ?
??????? ??????? ?????????
38
Transcription regulatory network in bakers
yeast

• Downloaded from the YPD database 1276
  regulations among 682 proteins by 125
  transcription factors (10 regulated genes per TF)
• Part of a bigger genetic regulatory network of
  1772 regulations among 908 proteins
• Positive to negative ratio 31
• Broader distribution of out-degrees (up to 72)
  and more narrow of in-degrees (up to 21)

39
????????? ???????????? (??????, ChIP-chip)

• A in-degree (???????????? ???????????? ?????)
  ??????????? (? ??????????????????? ???????????)
  ?????????? ?????????? ? ???????? ??????
  ??????????? ???????????????? ????????????? (?
  ??????????? ????? ???? ???????????). ??????
  ?????? ????????? ????
• ? out-degree (???????????? ????????)
  ??????????? ?????????? ????????, ???????????
  ???????? ?????????? ?????????? scale-free

40
Transcription regulatory network in Homo Sapiens

• Data courtesy of Ariadne Genomics obtained from
  the literature search 1449 regulations among 689
  proteins
• Positive to negative ratio is 31 (again!)
• Broader distribution of out-degrees (up to 95)
  and more narrow of in-degrees (up to 40)

41
Transcription regulatory network in E. coli

• Data (courtesy of Uri Alon) was curated from the
  Regulon database 606 interactions between 424
  operons (by 116 TFs)
• Positive to negative ratio is 32 (different from
  eukaryots!)
• Broader distribution of out-degrees (up to 85)
  and more narrow of in-degrees (only up to 6 !)

42
??????????? ??????????????? ? ???????? ??????? ??
?????????

• ??????
• 10 genes with lt5 links are essential
• gt60 genes with gt15 links are essential
• ???? ? ??????? ?????? ??????
• ? ??????? ???????????? ????? ????????? ?
  ?????????????? ??????????
• ????? ? ????????? ?? C. elegans

43
?????? ???? ? ??????

• PPI ????????? ?????-???????? ??????????????
• EL ??????? ??????????
• KE ??????????? ????????
• ER ???????? ????????
• PGL ??????????? ?????? ? ??????
• NP ?????????? ?????????
• GI ?????????? ???????? ?????????????

?.?.?????
44
party hubs ? date hubs

• ??????????? ????????????? ?????????? ??????
  ??????????
• ??????? hubs
• ??????? non-hubs
• ?????? ????????? ????
• Party hubs ??? ? ?????? ??-???????????????
  (?????????)
• Date hub ??? ?????????? ? ??????? ??????????
  (?????????? ????)

Han et al., 2004
45
???????????? ? ????? (?????????? ??????????
??????????)?????? ???? party hubs

• ??????? ????? ?? party hubs
• ?????????? ????? ?? ??? ????
• ??????? ????? ?? date hubs
• ??????? ????? ?? ????????? ?????

46
??????

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

47
???????????? ??????

• R ???????????????? ?????????
• ? ??-??????????

Zhang et al. 2005
48

• R ???????????????? ?????????
• ? ?????-???????? ??????????????
• ? ?????????

49
??????????? ???????? ????????????

• R ???????????????? ?????????
• ? ?????-???????? ??????????????
• ? ?????????

50

• R ???????????????? ?????????
• ? ?????-???????? ??????????????
• ? ??-??????????
• ? ?????????

51
????????

• R ???????????????? ?????????
• ? ?????-???????? ??????????????
• ? ??-??????????
• ? ?????????

52

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

53
??-?????????? ? ??????????

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

54
????????? ???????????? ? E.coli

• ????? ??? bi-fan ?????? ??????? ???? ? ??????

55

• ?????? ?????? Brookhaven Natl. Lab.
• ?????? ?????? ? ?????? ??????, MIT
• ?????? ?????????????? ?????

• ????
• ???
• HHMI
• LICR