The TRANSFAC ® System comprises 7 databases: TRANSFAC ® Professional Suite TRANSFAC ® Professional Transcription factor database TRANSCompel ® Professional Composite elements database PathoDB ® Professional Pathologically altered transcription factors TRANSPRO™ Professional Collection of human promoter sequences S/MARt DB™ Professional Scaffold or Matrix Attached Regions databases Cytomer ® Ontology of cells, structures, organs TRANSPATH ® Professional Signal transduction pathways
The TRANSFAC ® System comprises 7 databases: TRANSFAC ® Professional Suite TRANSFAC ® Professional Transcription factor database TRANSCompel ® Professional.
Jan 05, 2016
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The TRANSFAC® System comprises 7 databases:
TRANSFAC® Professional Suite
TRANSFAC® Professional
Transcription factor database
TRANSCompel® Professional
Composite elements database
PathoDB® Professional
Pathologically altered transcription factors
TRANSPRO™Professional
Collection of human promoter sequences
S/MARt DB™Professional
Scaffold or Matrix Attached Regions databases
Cytomer® Ontology of cells, structures, organs
TRANSPATH® Professional
Signal transduction pathways
One function – many structures (There‘s more then one way to do it)
One structure – many functions(Multipurpose structure of promoters)
Composite modules
organ,tissue,cell stage of
development
cell cyclephase
extracellularsignals
Composite modules encode gene expression pattern
human TNF promoter
mast cells
T-cells + ?
dendritic cells
T-cells
-107 -74
NFAT
NFATAP-1
NF-kB
C/EBPAP-1
VDR
gherllojunomd-bype Genny fasltow
Several regulatory messages could be written in thesame sequence. Reading of the messages depends on the
cellular context
gherllojunomd-bype Genny fasltow
1)
gherllojunomd-bype Genny fasltow 2)
gherllojunomd-bype Genny fasltow 3)
Composite modules
w
...
Start of transcription
)1(offcutq
)2(offcutq
)(koffcutq
)1( )2( )(k
...
...
...
Kk
kavr
k
wwqC
,1
)()( )(max )()( wq kavr
)1(1s
)2(1s
)(1
ks )(knk
s...
Parameters of the model to be estimated
)2(2s
K - number of TF matrixes
ws
qsqni
ki
ki
koffcut
ki
k
sq
)(
)()( )(,1
)( )(
• Extract promoters from TRANSPRO
• Run TRANSPLORER
• Run CMFinder (Composite Module Finder)
• Select matrices
• Find corresponding TFs in TRANSFAC
• Run ArrayAnalyser in TRANSPATH to find key molecules
Composite modules
Search for most probable binding sites regulating gene expression
Histogram of the composite score distance = 0.801300 Y:1.128014[0.985574] N:0.185089[0.557938] (FN=0.360000 FP=0.110294 T-test=9.141221) [ 0.0000 0.3159] |******************************* |############################### [ 0.3159 0.6318] | | [ 0.6318 0.9477] | | [ 0.9477 1.2636] |* |####### [ 1.2636 1.5795] |** |################# [ 1.5795 1.8954] |* |##################### [ 1.8954 2.2113] |* |#### [ 2.2113 2.5272] |* | [ 2.5272 2.8431] | | [ 2.8431 3.1590] |* |####### Matrices selected: V$VDR_Q3 V$AP1_01 V$NFKB_Q6_01 V$NFAT_Q6 V$AP1_01 V$NFAT_Q6 Pairs of matrices: P0 V$VDR_Q3(0.685500)-4:15-V$AP1_01(0.811500) Avr.score: Y:0.365517 N:0.076212 P1 V$NFKB_Q6_01(0.849500)-4:15-V$NFAT_Q6(0.854500) Avr.score: Y:0.096257 N:0.025980 P2 V$AP1_01(0.858500)-4:15-V$NFAT_Q6(0.854500) Avr.score: Y:0.666240 N:0.082897
Fuzzy puzzle hypothesis of the multipurpose structure of the eukaryotic promoters: of coding multiple regulatory messages in the same DNA sequence. A,B,C and D,E,F – two sets of TF; 1,2 – two sites in DNA; BC – basal complex.
A B C
D EF
B C
BC
1
2
1
2
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