2. Elsevier in the Classroom
Using Pathway Studio as a tool in the college
classroom to teach science interactively
Program Components
• Pathway Studio licenses will be provided to teachers and students for the duration of the teaching period
free of charge
• Teachers will be provided with a series of Pathway Studio teaching module examples designed to provide
comprehensive training in the full use of the Pathway Studio software set within a Systems Biology context.
• Additional instructional assistance will be available in the form of pre-recorded webinars
• Structured feedback will be requested from teachers during and at the end of each course in order to
provide data for future program modifications
• Collaborations will be offered as requested for the development of targeted course curriculum
• Participation in the publication of teaching results in education journals will be encouraged
• Pilot programs have already been initiated at Georgetown University, and will be extended to Virginia
Commonwealth University (VCU), MD Anderson, and Northeastern.
• Going forward, we will target universities on the strategic top 100 list, and also those that are clustered
near major pharmaceutical hubs (e.g. Boston).
• Teaching of courses to begin as soon as the Fall Semester, 2016
4. Pre-eclampsia or preeclampsia (PE) is a disorder of
pregnancy characterized by high blood pressure and
a large amount of protein in the urine. The disorder
usually occurs in the third trimester of pregnancy
and gets worse over time. In severe disease there
may be red blood cell breakdown, a low blood
platelet count, impaired liver function, kidney
dysfunction, swelling, shortness of breath due to
fluid in the lungs, or visual disturbances.
Preeclampsia increases the risk of poor outcomes for
both the mother and the baby. If left untreated, it
may result in seizures at which point it is known as
eclampsia.
Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit
organization.
Elsevier in the Classroom; Training Module 1
(disease-centric analysis)
1
5. Find all pre-
eclampsia
disease
relations
with protein
as an entity
type, select
all reference
>=10
What are the most important proteins
related to pre-eclampsia as found in the
scientific literature?
SAVE ALL WORK!
2
6. Select protein
most highly cited
in connection
with pre-
eclampsia (FLT1)
Find proteins
(transcription
factors) that bind
to the promoter
of FLT1
Highlight most cited
transcription
factor for FLT1
(HIF1A)
What is the single most highly cited protein
related to pre-eclampsia and what is it’s
most common transcription factor?
SAVE ALL WORK!
3
7. Find predicted
miRNAs that may
regulate
expression of
FLT1
SAVE ALL WORK!
Highlight
predicted
(red) vs
experimental
(green)
miRNAs
for FLT1
Are there any miRNAs which affect the
expression of the FLT1 gene? 4
8. Find proteins, protein complexes, protein functional
classes, and small molecules that are involved in the
expression FLT1, either directly or indirectly
(references >=10)
SAVE ALL WORK!
Highlight protein
functional classes
(red) and protein
complexes (green)
5
9. Identify groups of genes (from the list of proteins
most strongly associated with pre-eclampsia - slide 2)
that share common expression regulators using Sub-
Network Enrichment Analysis (SNEA).
Under Custom select type, use
“upstream” as the direction, “Protein”
as the entity (seed), and
“PromoterBinding” as the relation.
Name Total #of Neighbors Gene Set Seed Overlap Percent Overlap Overlapping Entitiesp-value Jaccard similarityHit type
Downstream Neighbors of JUN 331 JUN 24 7 EDN1;INHBA;MIR155;ACE;VEGFA;IL6R ligand;H1.79E-19 0.069565 Downstream N
Downstream Neighbors of HIF1A 248 HIF1A 17 6 EDN1;ADM;HIF1A;ACE;VEGFA;IL6R ligand;gela7.76E-13 0.063197 Downstream N
Downstream Neighbors of ATF2 89 ATF2 12 13 ACE;HIF1A;VEGFA;SELE;NOS3;gelatinase B;TN1.5E-12 0.104348 Downstream N
Downstream Neighbors of EP300 220 EP300 16 7 EDN1;VCAM1;HIF1A;VEGFA;NOS3;IL6R ligand;1.89E-12 0.066116 Downstream N
Downstream Neighbors of CEBPB 300 CEBPB 16 5 CRP;EDN1;ADM;GSTP1;VEGFA;IL6R ligand;TNF2.16E-10 0.049689 Downstream N
Downstream Neighbors of ETS1 170 ETS1 13 7 VCAM1;ACE;VEGFA;NOS3;gelatinase B;TNF;SE2.16E-10 0.066667 Downstream N
Downstream Neighbors of FOS 171 FOS 13 7 VCAM1;MIR155;GSTP1;VEGFA;IL6R ligand;gela2.33E-10 0.066327 Downstream N
Downstream Neighbors of STAT3 309 STAT3 16 5 CRP;ADM;MIR155;HIF1A;VEGFA;IL6R ligand;NO3.36E-10 0.048338 Downstream N
Downstream Neighbors of EGR1 232 EGR1 14 6 ACE;HIF1A;VEGFA;IL6R ligand;gelatinase B;TN8.51E-10 0.054688 Downstream N
6
10. SAVE ALL WORK!
Highlight the
pre-eclampsia
genes for the
two most
common
upstream
expression
regulators (JUN
in red, HIF1A in
green) as
revealed in the
SNEA analysis
(SEE BELOW FOR
HELP).
How many of the pre-eclampsia genes (from slide 2)
share either of the top 2 FLT1 transcription factor
regulators?
Pathway Studio Trick # 1!
7
11. This may not be obvious (at first!), but the way to highlight proteins/genes in a
pathway view with information from another group is actually quite easy! Just follow
the trail of bread crumbs below.
So, in the current example, in slide 7, we generated a list of the most common
upstream regulators for the pre-ecalampsia related genes (from slide 2) using
the SNEA tool. The top 2 entries (sorted by p-value) in that list (as found in the
table below the pathway viewer) are JUN and HIF1A.
8
12. To view the overlapping genes (from
your target list) with the list of all the
potential targets of say, in this case,
the JUN transcription factor, just
double-click on the particular list
entry in the table, and….voila, now
those genes (and those genes only)
are displayed in the pathway viewer.
1
Downstream Neighbors of
JUN
9
13. Now, here’s the big trick-> if you want
to highlight just those genes in another
pathway, all you have to do is: select
and copy them, now go to the other
pathway (drum roll, please!)
and … Select clipboard content and then
Highlight with the color of your choice
(hint: if you are going to highlight more
that once , the second time use a Mix-in
contrasting color so you can see both
highlights together).
2
See how easy that was? Now, why
don’t you try it with HIF1A!
10
14. HIF1A is not only one of the most important regulators of the FLT1 gene (which in
turn is the single most highly cited gene in reference to pre-eclampsia in the
literature), it also appears to be a major regulator for a significant number (17/41)
of all the pre-eclampsia associated genes.
This is beginning to look interesting, so what can we
tell about the biological processes controlled by
HIF1A?
Well, first of all, we could
Identify all the genes with
promoters known to be bound
by HIF1A.
Hint: Copy and paste
HIF1A into new
pathway, select HIF1A,
select add neighbors,
(downstream), select
Protein as the entity
type and
PromoterBinding as the
relation type
11
SAVE ALL WORK!
15. Now we can ask ourselves; of all the genes
under the potential control of HIF1A, what are
some of the most common biological processes
involved?
Select all from slide 11, go to tools, select enrichment analysis, analysis type = find pathways,
choose from the GO sets; biological processes, and then select ‘find’.
12
16. The most enriched GO biological
process for the HIF1A transcriptome
is…?
What diagnostic parameter (see slide 1) of pre-ecalampsia does
this finding make the most sense of? Discuss with class.
13
17. 14
Are you ready for a little bit more?
What about the drugs and possible drug
treatments that are used for handling
patients (i.e. pregnant women) at risk for
preeclampsia?
18. We have two quick ways (at least!) of investigating that question
using Pathway Studio
1. Test all small molecules associated in the literature with pre-eclampsia
2. Look for any clinical trials reported for pre-eclampsia treatments
15
19. Create a new pathway using the pre-eclampsia disease entity as a starting point.
Add small molecules as an entity type and relation = regulation, effect = negative.
This will still give you a lot of relations!
So let’s filter that down a little bit by
going to the Interactive Network
Builder and selecting for relations
with 5 or more supporting articles.
Now that’s a
little more
manageable!
Let’s go look
at the graph
view.
16
20. Looking good!
And if we look a the relation table
view and sort by the highest
number of references and we
find…aspirin!
Try googling aspirin and pre-
eclampsia and tell the class what
you find.
How is MgSo4 used in the treatment
of pre-eclampsia?
For what disease condition was
the drug pravastatin originally
developed for?
17
21. And finally, clinical trials
Small molecules, same as before, for relations pick ClinicalTrial
1. What are the most studied drugs in terms of number of
clinical trials?
2. What is the rationale for the use of pravastatin in treating
pre-eclampsia (requires linking out to the clinical trials
record for answer. Hint: check Detailed Description field)
18
