1.3 atsushi_doi@cell-innovator.com 6-10-1 I 2 http://www.cell-innovator.com 1
2
23andMe, GeneQuest, MYCODE DNA RNA
DNA RNA DNA A, T, G, C RNA or =
BioCyc (EcoCyc) KEGG Reactome WikiPathways TRANSPATH (BIOBASE) Ingenuity Pathway Analysis (IPA) NextBio PathwayStudio -> -> -> Elsevier
DAVID (Pathways in Cancer, Drug metabolism, ECM receptor interaction )
BioCyc (EcoCyc) KEGG Reactome WikiPathways TRANSPATH (BIOBASE) Ingenuity Pathway Analysis (IPA) PathwayStudio
(PPI: protein-protein interaction) EBI BioGRID IPA BIOBASE, JASPAR, MSigDB GeneMANIA COXPRESdb KEGG, BIOBASE, IPA, PathwayStudio, GeneSpring
ARACNE: Mutual information BANJO: Bayesian inference CLR: Mutual information MIKANA: Dynamic systems SiGN-BN: Bayesian inference
or ARACNE SiGN BIOBASE IPA KEGG GeneSpring PathwayStudio
1. 2. 3. 15
1. 16
BP -- http:// special.nikkeibp.co.jp/ts/article/aaaa/114314/ Google Facebook Amazon 25 http:// www.nikkei.com/article/dgxnzo57421630x10c13a7ea1000/ 17
Moneyball: The Art of Winning an Unfair Game 2 March 17, 2004 by Michael Lewis 18
20 19
2. 20
B 20 10 A 10 B 10 (x, y) = (10, 10) A 20 B 20 (x, y) = (20, 20) 0 10 20 A 21
(1) B 20 10 A B A B A B A B 0 10 20 A 22
(2) B 20 10 A B A B A B A B 0 10 20 A 23
20 20 B 10 A 10 0 10 20 0 10 20 A B X Y 24
??? 400 400 25
A B B C A B C 26
A B C A B C A B C 27
A B C B A C A B A B C A B C 28
A: B: C: A 70% C B 30% 29
A B?? C A --> C C --> A 30
B --> C --> A A? C B 31
B DAG Greedy Hill Climbing BNRC http://www.scls.riken.jp/scruise/software/sign-bn.html 32
3. 33
34
= Protein-Protein Interaction (PPI) network = = = 35
36
lincrna 37
NCBI Gene Expression Omnibus (GEO) --> Cancer Cell Line Encyclopedia (CCLE) 1000 [GSE36133] The Cancer Genome Atlas (TCGA) SCLS --> 38
39
logfc 40
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), 1469 1487. doi:10.1098/rstb.2007.2129 41
42
Gene Network of apoptosis related genes 43
ANXA5 (top gene) TP53 (bottom gene) 44
ANXA5 TP53 regulating genes TP53 45
Big pharma shows signs of renewed interest in RNAi drugs Nature Medicine 20, 109, 2014. PCSK9 is the target gene of Alnylam RNAi drug. * Lancet 383, 60-68, 2014.
PCSK9 in the gene network PCSK9 exists in the gene network of lipid metabolic process. (http:// gndb.cell-innovator.com/?page_id=92) 19 children and 3 parents.
Next genes of PCSK9? PCSK9 PCSK9? PCSK9 PCSK9 PCSK9 PSCK9 PSCK9 apoptosis
Stem Cell Sox2 Oct3/4 Klf4
Pou5f1 = Oct3/4 Zscan10 Zscan4a Nanog? Tcl1?
Stem Cell GEO BioGPS Oct3/4 180 Sox2 Klf4 Stem Cell SiGN-BN
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.
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