Well-Annotated Functional Pathway

Question

[Andrew Su]

The dilemna: I am submitting a grant proposal tomorrow morning. However, inspiration hit this morning and I need to make a new figure on short notice.

The need: My new figure will describe a well-annotated biological pathway. Here are the specific requirements:

• 10-20 pathway members
• edges must define functional relationships, not the experimental or analytical technique used to determine the edge (e.g., yeast two hybrid, co-expression, literature cooccurrence)
• functional edge types that are wanted include (but are not limited to):
  • Transcriptional activation/repression
  • Phosphorylation/dephosphorylation
  • Protein cleavage
  • Glycosylation
  • Methylation
  • Other physical interaction

Note, I'm not looking for someone to identify pathway members, then pull out edges from PPI/coexpression databases. I'm looking for an expert-curated pathway diagram, perhaps from a review article on the topic or perhaps one of the curated pathway databases.

Edit: Networks do not need to be annotated with rate constants and the like. I am interested a qualitative description of a gene network...

Edit: Ideally, I'm looking for a network that has multiple edge types listed above...

The reward: Recognizing the urgency of my request, I'm mortgaging another 250 reputation points for the best answer. However, only answers in the next six hours are eligible. (Note the bounty will be entered in the system as soon as I'm able -- after a few days I think. But again, I need your answers now!)

The bonus: I will add an additional 100 reputation points to the bounty if the pathway is specifically on the Regulatory T cell differentiation pathway.

[Andrew Su]

Biostar is just awesome. That is all...

[Andrew Su]

Thanks to everyone who gave answers. Very helpful! In addition to the specific examples given, I learned (or was reminded) that biocarta.com, reactome.org, cellsignal.com, and qiagen.com are all great resources for beautiful illustrations of well-annotated pathways. Wikipathways (which I love) has great breadth but lacks the artist's touch.

In any case, I'm awarding the bounty to Alex Paciorkowski for the answer that ended up being most helpful for the grant proposal. Thanks all!

Answer 1

[Alex Paciorkowski]

The 2 very well annotated functional pathways that come to mind for me are (1) the MTOR pathway and (2) the RAS pathway.

Here are some references with figures:

MTOR

Swiech, et al 2008, Zeng, et al 2010

RAS

Tidyman & Rauen, 2009

If the figures are not in the format you wish, you can easily extract the genes involved and build your own figures in Biotapestry for transcription factors, and ProteinLounge or String to show other types of functional relationships.

Hands down, one of the best functional figures I have seen yet is of the synapse.

I don't know of any specific T cell regulatory pathways at my fingertips, as that's not my field of expertise.

Good luck with your submission!

[Andrew Su]

Figure 1 of Swiech is pretty outstanding. Good one!

[Larry_Parnell]

I like MTOR because of its relevance to insulin signaling, diabetes and aging.

Answer 2

[Sean Davis]

You might take a look at wikipathways and reactome.

[Andrew Su]

thanks for the links. Yes, I'm aware of and love both those sites, but quality does vary. If anyone has specific pathways that they know to be high quality, please submit that as an answer...

Answer 3

[Casey Bergman]

Neither are T cell development but these examples from Levine & Davidson (2005) are highly curated and have multiple node types:

1) Endoderm development in the sea urchin:

OR

2) Dorsal-ventral development in the fly:

Answer 4

[Madhan]

Hi Andrew Su,

I often use SigmaAldrich.com site to get the annotated information about the pathways. See if this can be useful to you.

T cell differentiation Pathway:

http://www.sigmaaldrich.com/catalog/ProductDetail.do?&F=CP&ST=YFG&IID=ING:3qbdh

[Madhan]

You can Zoom in and click on the links to know the type of interaction.

[Andrew Su]

Thanks for the pointer. Not bad... It identifies the right genes but the edge types are a little more rudimentary than I was hoping to find.

Answer 5

[Mary]

Something like this? http://www.biocarta.com/pathfiles/h_il7Pathway.asp

[Andrew Su]

That one's pretty darn good. The edge types in the figure aren't typed, but the relationships are described in the caption. Nice one, Mary...

Answer 6

[julieN]

my two cents:

http://www.cellsignal.com/pathways/lymphocyte.jsp

Answer 7

[Larry_Parnell]

I would consider the epidermal growth factor receptor signaling network. This is a go-to pathway in systems biology for those interested in relationships of entities at the biological levels as well as describing those relationships with differential equations. The EGFR pathway is important in development and in cancer.

I do not know a specific citation, but would start with work (original research or review) by Walter Fontana.

Answer 8

[Larry_Parnell]

A second answer - different from the first, mainly because of its familiarity. Try the cell cycle.

There are some nice cell cycle pathways at cellsignal.com. I particularly like the "nodes" of caffiene, DNA, UV light, and the hierarchy of signals leading to a G2 to M transition. The G1/S checkpoint also looks good.

Answer 9

[ALchEmiXt]

Are these qiagen pathways too high meta-level? They are quite illustrative and on many topics including many aspects of T-cell differentiation and maturation... (not including the specifics of actions usually though (edit: see keys since they do... my bad)

e.g. https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=240

Keys: https://www.qiagen.com/geneglobe/help/pathwaykey.aspx

Other pathways at qiagen: https://www.qiagen.com/geneglobe/pathways.aspx

[proteinlounge]

The Qiagen pathways were all done by the protein lounge team so you may want to go to http://www.proteinlounge.com to get the most currently updated pathways.