遺伝子ネットワーク解析

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1 I 2 1

2 2

3 23andMe, GeneQuest, MYCODE DNA RNA

4 DNA RNA DNA A, T, G, C RNA or =

5

6 BioCyc (EcoCyc) KEGG Reactome WikiPathways TRANSPATH (BIOBASE) Ingenuity Pathway Analysis (IPA) NextBio PathwayStudio -> -> -> Elsevier

7

8 DAVID (Pathways in Cancer, Drug metabolism, ECM receptor interaction )

9

10 BioCyc (EcoCyc) KEGG Reactome WikiPathways TRANSPATH (BIOBASE) Ingenuity Pathway Analysis (IPA) PathwayStudio

11 (PPI: protein-protein interaction) EBI BioGRID IPA BIOBASE, JASPAR, MSigDB GeneMANIA COXPRESdb KEGG, BIOBASE, IPA, PathwayStudio, GeneSpring

12

13 ARACNE: Mutual information BANJO: Bayesian inference CLR: Mutual information MIKANA: Dynamic systems SiGN-BN: Bayesian inference

14 or ARACNE SiGN BIOBASE IPA KEGG GeneSpring PathwayStudio

15

16 1. 16

17 BP -- special.nikkeibp.co.jp/ts/article/aaaa/114314/ Google Facebook Amazon

18 Moneyball: The Art of Winning an Unfair Game 2 March 17, 2004 by Michael Lewis 18

19 20 19

20 2. 20

21 B A 10 B 10 (x, y) = (10, 10) A 20 B 20 (x, y) = (20, 20) A 21

22 (1) B A B A B A B A B A 22

23 (2) B A B A B A B A B A 23

24 20 20 B 10 A A B X Y 24

25 ???

26 A B B C A B C 26

27 A B C A B C A B C 27

28 A B C B A C A B A B C A B C 28

29 A: B: C: A 70% C B 30% 29

30 A B?? C A --> C C --> A 30

31 B --> C --> A A? C B 31

32 B DAG Greedy Hill Climbing BNRC 32

33 3. 33

34 34

35 = Protein-Protein Interaction (PPI) network = = = 35

36 36

37 lincrna 37

38 NCBI Gene Expression Omnibus (GEO) --> Cancer Cell Line Encyclopedia (CCLE) 1000 [GSE36133] The Cancer Genome Atlas (TCGA) SCLS --> 38

39 39

40 logfc 40

41 Affara, M., Dunmore, B., Savoie, C., Imoto, S., Tamada, Y., Araki, H., Charnock-Jones, D. S., et al. (2007). Understanding endothelial cell apoptosis: what can the transcriptome, glycome and proteome reveal? Philosophical transactions of the Royal Society of London Series B, Biological sciences, 362(1484), doi: /rstb

42 42

43 Gene Network of apoptosis related genes 43

44 ANXA5 (top gene) TP53 (bottom gene) 44

45 ANXA5 TP53 regulating genes TP53 45

46 Big pharma shows signs of renewed interest in RNAi drugs Nature Medicine 20, 109, PCSK9 is the target gene of Alnylam RNAi drug. * Lancet 383, 60-68, 2014.

47 PCSK9 in the gene network PCSK9 exists in the gene network of lipid metabolic process. ( gndb.cell-innovator.com/?page_id=92) 19 children and 3 parents.

48 Next genes of PCSK9? PCSK9 PCSK9? PCSK9 PCSK9 PCSK9 PSCK9 PSCK9 apoptosis

49 Stem Cell Sox2 Oct3/4 Klf4

50 Pou5f1 = Oct3/4 Zscan10 Zscan4a Nanog? Tcl1?

51 Stem Cell GEO BioGPS Oct3/4 180 Sox2 Klf4 Stem Cell SiGN-BN

52 Oct3, Sox2, Klf4 Oct3, Sox2, Klf4 Klf4 Zscan4a 3 Sox2 * Oct3/4 * Jing Jiang et. al., Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of ips cells as demonstrated by tetraploid complementation. Cell Res. (2012) : 1-15.

53 53

54 XXX 54

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