Filtering information from metabolic model

[Deepa Maheshvare]

Hello everyone,

I have loaded the metabolic model(Recon 2.2) in Cytoscape.I would like to filter the set of pathways that correspond to glucose metabolism .Could you please guide me with the steps to do it?

Thanks,

Deepa

[Piet]

Hi Deepa,

I'm not totally familiar with the annotation of the pathways in the Recon metabolic model, but I assume that some kind of annotation includes the terms glucose metabolism; you should be able to filter for the pathways involved using the filter options in Cytoscape (http://manual.cytoscape.org/en/stable/Finding_and_Filtering_Nodes_and_Edges.html#filters)

Let me know if that doesn't solve your problem,

Regards,

Piet

Op donderdag 22 juni 2017 04:00:49 UTC+2 schreef Deepa Maheshvare:

[Matthias König]

Hi Deepa,
just read the model with cy3sbml (this is the cys I send you for Recon2).
I read the SUBSYSTEM information for all nodes into the SUBSYSTEM column of nodes where you can filter.
The subsystem you are looking for in Recon2 is 'Glycolysis/gluconeogenesis'.
Make sure you are in the Base Network, i.e. Network -> Base (this is the species-reaction graph)

To Filter do

Control Panel -> Select -> '+' -> Column Filter
choose column -> Node:SUBSYSTEM, term: glycolysis

This selects all reaction nodes annotated with the subsystem.
The problem with metabolic models like RECON2 is that only the reactions are annotated to subsystems, but you also want the species in the reaction-species graph of the subsystem.
Because the graph is bipartite, you can just select the next neighbors of the selected subsystem:
I.e.
Select -> Nodes -> First Neighbors of selected Nodes -> undirected (Ctrl + 6)

Now you have all reactions and the involoved species selected.

Create a new subnetwork via
File -> New Network -> From Selected Nodes All Edges (Ctrl + N)

Apply Layout to pull the network together:
Layout -> Prefuse Force Directed Layout (this works well in metabolic networks)

M

[Deepa Maheshvare]

Hi Piet and Matthias,

Thanks a lot for all your valuable suggestions.

I followed the steps mentioned by Matthias in the above respone. I would like to know why the Glycolysis pathway appear in fragments(Please have a look at the file).Why is the network not connected  on the whole?

Kindly correct me if I have made any mistake.

I used the Save ->style(xml) icon to save the file.I wish to load this file in COPASI,with the rate equations that correspond to the pathway in the filtered network.

When I load the file into COPASI,after filtering in cytoscape,I am not able to view any of the data in copasi.

Could you pleas tell me how this can be done? 

Thanks again,

Deepa

[Deepa Maheshvare]

Hi All,

I have attached the session files in this link .

A. glycolysis.cys is generated on cytoscape using the Recon 2.2 from biomodels database.

B. glycolysis_wiki.cyc is generated on cytoscape using the wiki pathways.

 

In flie A,the pathway is not interconnected on the whole.I would like to obtain something similar to the pathway in File B. Also,can we change the settings to connected all the fragments in File A?

Thanks,

Deepa

[Matthias König]

Hi Deepa,

Here some short answers. Only on mobile now.

Not connected:

- the annotations of subsystems are not very good. Especially transporters are often not annotated correctly or at all. Part of the reactions are in other compartments. So disconnected if transporters don't have subsystem. A better way to annotate pathways is via sbml groups, but not available for recon 2.

- kinetics are not part of recon2. This is a stoichiometric reconstruction for fba analysis or similar constraint based mehthods. So no kinetic information in the model and you don't see anything in copasi.

The step from stochiometric to kinetic model takes a lot of work and domain knowledge. No simple solution here.

M

--
You received this message because you are subscribed to a topic in the Google Groups "cytoscape-helpdesk" group.
To unsubscribe from this topic, visit https://groups.google.com/d/topic/cytoscape-helpdesk/Dkxp6RMK5Tg/unsubscribe.
To unsubscribe from this group and all its topics, send an email to cytoscape-helpdesk+unsub...@googlegroups.com.
To post to this group, send email to cytoscape-helpdesk@googlegroups.com.
Visit this group at https://groups.google.com/group/cytoscape-helpdesk.

To view this discussion on the web visit https://groups.google.com/d/msgid/cytoscape-helpdesk/1517d8b7-e906-4169-969b-b00abbc22800%40googlegroups.com.

For more options, visit https://groups.google.com/d/optout.

[Deepa Maheshvare]

Hi Matthias,

Thanks a lot for all your valuable inputs.Can I ask a few more questions, if you don't mind?

I wish to study the glycolytic pathway in pancreas of humans in connection with Diabetes Mellitus .

I would like to know if it would be a good choice to consider 

(i)the metabolic pathway developed for the glucose metabolism in the pancreas of rodents (ref1)or

(ii)can we use the pathway which is developed for the glucose metabolism in human liver.(ref2) to study the glycolytic pathway in pancreas of humans ?

Would the sequence of reactions that occur during glycolysis differ in each organ ?

I observe that the glycolytic pathway shown in ref 1 and ref 2 are different. For instance,the PEP transporter listed in ref 2 is not included in the model shown in ref1. 

Will the reaction pathway for  glucose metabolism in liver differ from that of the pancreas?

Kindly excuse me for asking elementary questions.

[Matthias König]

Hi Deepa,

depending on the tissue glycolysis pathway looks a bit differeent. The liver and kidney are organs which are able to produce glucose under low glucose conditions, i.e. hypoglycemia. Consequently liver/kidney models contain reactions necessary to convert the precursors of glucose to glucose, for instance PEPCK, but also the FBPase or glucose-1p deposphorylase.

These models have mainly the function of switching between glucose production and glucose consumption.

So some of the reactions are different in the model (mainly different patterns of expression of key isoforms in a tissue-specific manner).

The pancreas on the other hand is mainly glycolytic, but still has special isoenzymes, like the Glucokinase instead of Hexokinase in combination with glucose transporters like GLUT2 if I remember correctly (with high Km values).

So the better choice is definitely a pancreas specific model.

The Ref1 looks good and If I were you I would try to get simulations running with it (for instance using libroadrunner).

If you are going for a kinetic model it makes sense to build on existing kinetic models for the given tissue. Often the same isoforms in rat/human have very similar Km values at least (not necessarily Vmax values).

M

--
You received this message because you are subscribed to a topic in the Google Groups "cytoscape-helpdesk" group.
To unsubscribe from this topic, visit https://groups.google.com/d/topic/cytoscape-helpdesk/Dkxp6RMK5Tg/unsubscribe.
To unsubscribe from this group and all its topics, send an email to cytoscape-helpdesk+unsub...@googlegroups.com.
To post to this group, send email to cytoscape-helpdesk@googlegroups.com.
Visit this group at https://groups.google.com/group/cytoscape-helpdesk.

To view this discussion on the web visit https://groups.google.com/d/msgid/cytoscape-helpdesk/CAGchuN4eZx5-C9W6o%2BLddP-4_w2hwTA8DH8JYC250-_CEjEdOA%40mail.gmail.com.

For more options, visit https://groups.google.com/d/optout.

--

Dr. Matthias König
Junior Group Leader LiSyM - Systems Medicine of the Liver
Humboldt-University Berlin, Institute of Biology, Institute for Theoretical Biology
  https://www.livermetabolism.com
koni...@googlemail.com
Tel: +49 30 20938450
Tel: +49 176 81168480

[Matthias König]

Hi Deepa,

here just some short update.

The pancreas model looks good and reproduces the results from the figure.

How to run simulations with the model you can see in the following notebook.
https://github.com/matthiaskoenig/sbmlutils/blob/dfba-uniqueness/oven/pancreas/pancreas.ipynb

M

On Mon, Jun 26, 2017 at 2:04 PM, Matthias König <koni...@googlemail.com> wrote:

Hi Deepa,

depending on the tissue glycolysis pathway looks a bit differeent. The liver and kidney are organs which are able to produce glucose under low glucose conditions, i.e. hypoglycemia. Consequently liver/kidney models contain reactions necessary to convert the precursors of glucose to glucose, for instance PEPCK, but also the FBPase or glucose-1p deposphorylase.

These models have mainly the function of switching between glucose production and glucose consumption.

So some of the reactions are different in the model (mainly different patterns of expression of key isoforms in a tissue-specific manner).

The pancreas on the other hand is mainly glycolytic, but still has special isoenzymes, like the Glucokinase instead of Hexokinase in combination with glucose transporters like GLUT2 if I remember correctly (with high Km values).

So the better choice is definitely a pancreas specific model.

The Ref1 looks good and If I were you I would try to get simulations running with it (for instance using libroadrunner).

If you are going for a kinetic model it makes sense to build on existing kinetic models for the given tissue. Often the same isoforms in rat/human have very similar Km values at least (not necessarily Vmax values).

M

On Mon, Jun 26, 2017 at 9:06 AM, Deepa Maheshvare <deepama...@gmail.com> wrote:

Hi Matthias,

Thanks a lot for all your valuable inputs.Can I ask a few more questions, if you don't mind?

I wish to study the glycolytic pathway in pancreas of humans in connection with Diabetes Mellitus .

I would like to know if it would be a good choice to consider 

(i)the metabolic pathway developed for the glucose metabolism in the pancreas of rodents (ref1)or

(ii)can we use the pathway which is developed for the glucose metabolism in human liver.(ref2) to study the glycolytic pathway in pancreas of humans ?

Would the sequence of reactions that occur during glycolysis differ in each organ ?

I observe that the glycolytic pathway shown in ref 1 and ref 2 are different. For instance,the PEP transporter listed in ref 2 is not included in the model shown in ref1. 

Will the reaction pathway for  glucose metabolism in liver differ from that of the pancreas?

Kindly excuse me for asking elementary questions.

--
You received this message because you are subscribed to a topic in the Google Groups "cytoscape-helpdesk" group.
To unsubscribe from this topic, visit https://groups.google.com/d/topic/cytoscape-helpdesk/Dkxp6RMK5Tg/unsubscribe.

To unsubscribe from this group and all its topics, send an email to cytoscape-helpdesk+unsubscribe@googlegroups.com.

To post to this group, send email to cytoscape-helpdesk@googlegroups.com.
Visit this group at https://groups.google.com/group/cytoscape-helpdesk.

To view this discussion on the web visit https://groups.google.com/d/msgid/cytoscape-helpdesk/CAGchuN4eZx5-C9W6o%2BLddP-4_w2hwTA8DH8JYC250-_CEjEdOA%40mail.gmail.com.

For more options, visit https://groups.google.com/d/optout.

--

Dr. Matthias König
Junior Group Leader LiSyM - Systems Medicine of the Liver
Humboldt-University Berlin, Institute of Biology, Institute for Theoretical Biology
  https://www.livermetabolism.com
koni...@googlemail.com
Tel: +49 30 20938450
Tel: +49 176 81168480

[Deepa Maheshvare]

Hi Matthias,

Thank you very much for the insightful explanation.I could reproduce the results using COPASI. I will definitely try libroadrunner too.

I was not convinced with using the model in ref1 because the taxonomy was mentioned to be mammalia(not homo sapiens) on biomodels database.Thanks for the clarification on similar isomers present in rat and humans.I will read on the determination of Vmax and proceed with the same.

Would it be meaningful to include PEPCK in the glycolytic pathway  that takes place in pancreas?

OA(mito) <---> PEP----> Lactate (cytosol)

 

In the absence of gluconeogenesis in the pancreas,PEP will not get converted back to 2PG. I believe, PEP formed from OA (catalysed by PEPCK) would  result in formation of  lactate in pancreas too.Please correct me if I am wrong.

Thanks a ton for all your support.

Deepa                            

You received this message because you are subscribed to the Google Groups "cytoscape-helpdesk" group.
To unsubscribe from this group and stop receiving emails from it, send an email to cytoscape-helpdesk+unsub...@googlegroups.com.

To post to this group, send email to cytoscape-helpdesk@googlegroups.com.
Visit this group at https://groups.google.com/group/cytoscape-helpdesk.

To view this discussion on the web visit https://groups.google.com/d/msgid/cytoscape-helpdesk/CAEUx3EQTDi1du%3D3pTJ5ORAiCKRsaM80PMschDAJ_sYgQZ2btCg%40mail.gmail.com.