| This example demonstrates how to create
biological signaling pathways in DSM Language from literature data
and how to produce editable signaling pathway maps.
You read a scientific article, for example:
Pernis, A.B. (2002) The Role of IRF-4 in B and T Cell Activation
and Differentiation, Journal of Interferon and Cytokine
Research 22:111–120
The signaling pathway data in this paper can be coded in DSM
Language as follows:
default[nucl];
NF-kB -> IRF4;
STAT6-P -> IRF4;
\IRF4, PU-1\ -> *Ig-K, Ig-L, CD20*;
\IRF4, Spi-B\ -> *Ig-k, Ig-l*;
\IRF4, E47\ -> *Ig-k, Ig-l*;
CIITA -> MHC_II;
@1 := {\NF-kB, STAT6-P, IRF4\ -> CD23};
PRDI-BF1 -| *IFN-b, CIITA, c-Myc, IRF4*;
PRDI-BF1 -| @1;
BCL6 -| *CD23, STAT6-P, IRF4*;
default[cytomb];
@2 := {STAT6 => STAT6-P};
(Ag, TCR) -> NF-kB;
(Ag, BCR) -> NF-kB;
(CD40, CD40L) -> NF-kB;
(CD40, CD40L) -| BCL6;
(IL4, IL4-R) -> @2;
(CD40, CD40L) -> BCL6;
# translocations
STAT6-P[cytomb] ~> STAT6-P[nucl];
NF-kB[cytomb] ~> NF-kB[nucl];
BCL6[cytomb] ~> BCL6[nucl];
|
In the Dynamic Signaling Maps console editor you can open an
empty DSM Language file and enter the text above:

After you Save the file you can click the
Translate button to verify the consistency of the data you
have just entered:

Oops! An inconsistency -- statements in lines 18 and 20
contradict each other. They represent the inhibition and
activation, respectively, of the BCL6 molecule by the same complex,
CD40 + CD40L.
We intentionally inserted line 20, which doesn't correspond to
any data in the article, to simulate a real-life situation where
data from different sources are contradictory and to show you how
the DSM Translator intercepts such situations. What you need to do
at this point, assuming you have determined that line 20 contains
wrong data, is simply delete all the text in the "textarea" element
below Edit line 20 in the dialog above and then hit the
Update, Save, & Translate again button:

Success! Now you can click the Map button and choose the
output format:

Here is a screen shot of your signaling map:

If you wish to "zoom in" on details of this map here it is in
PDF format. If you want to include and edit
it in a PowerPoint presentation then you can map out the signaling
pathway data in EMF format.
With an Internet-enabled computer handy you can enter the data
in the DSM console while you read the article at your desk, at the
library, or during your flight. In this particular example,
entering the signaling pathway data in DSM Language while you read
the article will extend your reading time by about ten minutes. And
the graphical map is just "one click away"!
If you actually try finding that journal then you will discover
a second article, on a very similar topic, in the same issue:
Marecki, S. and Fenton, M.J. (2002) The Role of IRF-4 in
Transcriptional Regulation, Journal of Interferon and Cytokine
Research 22:121–133
Want an updated signaling map, which also takes into account the
data in the second paper? Just edit your file in the DSM console
editor to include the new data and then hit Translate and
Map again — it's as simple as that!
Here is the signaling data corresponding to the second
article:
default[nucl];
PU-1-P -> *c-fms, Ig-k, Ig-l, Ig-m, CD11b, IL-1b, gp91PHOX*;
PU-1-P -> *Mf_scavenger_R, CD20, Mf_mannose_R*;
PU-1-P -| *I-Ab/MHC_II, MMP-1, CD11c*;
(IRF1, IRF1) -> MHC_I;
(IRF1, ICSBP) -| MHC_I;
*IRF4, ICSBP, IRF2* -| ISG15;
*ICSBP, IRF4* -| *_2-5-OAS, H-2Ld*;
ICSBP -> ICSBP;
ICSBP -> IL12;
@3 := {ISGF3g -> IFN-g_responsive_genes};
(ICSBP, ISGF3g) -| @3;
(IRF4, STAT6) -> CD23;
(IRF4, BCL6) -| CD23;
(IRF1, IRF2, IRF4, PU-1-P) -> IL1-b;
(ICSBP, PU-1-P) -> IL1-b;
@6 := {ICSBP -> IL18};
ICSBP -> CD11b;
@4 := {PU-1 => PU-1-P};
CK2 -> @4;
default[cytomb];
(IFN-g, IFN-g-R) -> II_msg;
II_msg[cytomb] ~> II_msg[cyto];
II_msg[cyto] -> MAPK[cyto];
CK2[cyto] ~> CK2[nucl];
@5 := {IRF4[cyto] ~> IRF4[nucl]};
LPS[extr] ~> LPS[cyto];
default[cyto];
\STAT, p48/IRF9\ => ISGF3g;
LPS -> MAPK;
MAPK -> CK2;
LPS -> @5;
MAPK -> STAT;
LPS[cyto] ~> LPS[nucl];
LPS[nucl] -> @6;
ISGF3g[cyto] ~> ISGF3g[nucl];
PU-1 == SPI-1;
ICSBP == IRF8;
|
Upon entering this data in a separate file and running
Translate and Map you get the signaling map below
(display it in PDF format):

To have the signaling data from both papers in one diagram you
can simply append the new data to the previous file. Here is the
combined data:
#JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 22:111–120 (2002)
# The Role of IRF-4 in B and T Cell Activation and Differentiation
# ALESSANDRA B. PERNIS
default[nucl];
NF-kB -> IRF4;
STAT6-P -> IRF4;
\IRF4, PU-1-P\ -> *Ig-K, Ig-L, CD20*;
\IRF4, Spi-B\ -> *Ig-k, Ig-l*;
\IRF4, E47\ -> *Ig-k, Ig-l*;
CIITA -> MHC_II;
@1 := {\NF-kB, STAT6-P, IRF4\ -> CD23};
PRDI-BF1 -| *IFN-b, CIITA, c-Myc, IRF4*;
PRDI-BF1 -| @1;
BCL6 -| *CD23, STAT6-P, IRF4*;
default[cytomb];
@2 := {STAT6 => STAT6-P};
(Ag, TCR) -> NF-kB;
(Ag, BCR) -> NF-kB;
(CD40, CD40L) -> NF-kB;
(CD40, CD40L) -| BCL6;
(IL4, IL4-R) -> @2;
# translocations
STAT6-P[cytomb] ~> STAT6-P[nucl];
NF-kB[cytomb] ~> NF-kB[nucl];
BCL6[cytomb] ~> BCL6[nucl];
PRDI-BF1 == Blimp1;
# JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 22:121–133 (2002)
# The Role of IRF-4 in Transcriptional Regulation
# SYLVIA MARECKI and MATTHEW J. FENTON
default[nucl];
PU-1-P -> *c-fms, Ig-k, Ig-l, Ig-m, CD11b, IL-1b, gp91PHOX*;
PU-1-P -> *Mf_scavenger_R, CD20, Mf_mannose_R*;
PU-1-P -| *I-Ab/MHC_II, MMP-1, CD11c*;
(IRF1, IRF1) -> MHC_I;
(IRF1, ICSBP) -| MHC_I;
*IRF4, ICSBP, IRF2* -| ISG15;
*ICSBP, IRF4* -| *_2-5-OAS, H-2Ld*;
ICSBP -> ICSBP;
ICSBP -> IL12;
@3 := {ISGF3g -> IFN-g_responsive_genes};
(ICSBP, ISGF3g) -| @3;
(IRF4, STAT6) -> CD23;
(IRF4, BCL6) -| CD23;
(IRF1, IRF2, IRF4, PU-1-P) -> IL1-b;
(ICSBP, PU-1-P) -> IL1-b;
@6 := {ICSBP -> IL18};
ICSBP -> CD11b;
@4 := {PU-1 => PU-1-P};
CK2 -> @4;
default[cytomb];
(IFN-g, IFN-g-R) -> II_msg;
II_msg[cytomb] ~> II_msg[cyto];
II_msg[cyto] -> MAPK[cyto];
CK2[cyto] ~> CK2[nucl];
@5 := {IRF4[cyto] ~> IRF4[nucl]};
LPS[extr] ~> LPS[cyto];
default[cyto];
\STAT, p48/IRF9\ => ISGF3g;
LPS -> MAPK;
MAPK -> CK2;
LPS -> @5;
MAPK -> STAT;
LPS[cyto] ~> LPS[nucl];
LPS[nucl] -> @6;
ISGF3g[cyto] ~> ISGF3g[nucl];
PU-1 == SPI-1;
ICSBP == IRF8;
|
Notes. (1) While in the first article explicit reference
is made to STAT6 and its phosphorylated form, in the second article
STAT proteins are only generically referred to; we have to leave it
like that until we can get more information on the particular STAT
proteins involved. (2) In the second paper, we get an interesting
piece of new information: PU.1 (or PU-1, above) needs to be
phosphorylated to be active. Since we entered this factor as PU-1
in the data from the first paper and as PU-1-P in the data from the
second paper, to avoid displaying it as two different molecules
(PU-1 and PU-1-P) we have edited line 8, which is based on data
from the first paper
\IRF4, PU-1\ -> *Ig-K, Ig-L, CD20*; |
as follows:
\IRF4, PU-1-P\ -> *Ig-K, Ig-L, CD20*; |
We can now run Translate and Map the combined
data:

Check out the final map in PDF format
and this file in PPT format produced after
some customization in PowerPoint.
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