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changwn / scFEA

single cell Flux Estimation Analysis (scFEA) Try the below web server!
http://scflux.org/
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Balance values interpretation #48

Open iichelhadi opened 9 months ago

iichelhadi commented 9 months ago

As others have indicated previously. It is not clear how to interpret the balance values (especially the negative values). Could you maybe explain it a bit more in simpler terms?

Joyjoyjoyc commented 7 months ago

hello, I have the same question, too. Did you got it? and i also wander what does a negative value of the flux mean? Thank you so much!!

LiuCanidk commented 6 months ago

@Joyjoyjoyc @iichelhadi image

According to the original paper (screenshot above), where the balance value was mentioned to indicate the metabolic stress, I speculate that positive values indicate accumulation of that metabolite, and negative values indicate depletion. As the figure below shown, control VS. treatment (Note that the comparing direction in the figure caption was opposite to the statement in the screenshot: APEX1-KD VS. control), G1P showed negative "imbalance value" (that is, the balance values, difference between in-out flux, as the screeshot states), so control has less G1P than treatment, so G1P was accumulating in treatment APEX1-KD, which was matched with the statement in the screenshot. image

And in our results of our data input, each sample or cell has a balance value, I think it is equal to the value of in-flux minus out-flux. So you would see in general all balance values, of the same type of metabolite, across the samples or cells, are all positive or are all negative, indicating their in-out direction and whether they are accumulating or depleting. So if you have samples or cells that has opposite balance values of the same metabolite, congratulation! You find significant metabolic rewiring! It worth an experimental validation!

Joyjoyjoyc commented 6 months ago

Hi, @LiuCanidk, thank you so much for your reply, and here is another question for me. In the tutorial2, the author embedded the fluxes predicted by scFEA into the scRNA-seq and preserve the sign of the fluxes. I wonder if it possible for me to use the absolute value of fluxes as I just want to focus on the amount of the fluxes as a representation for some metabolic pathways' activity but not the direction.

LiuCanidk commented 6 months ago

@Joyjoyjoyc

Hi, @LiuCanidk, thank you so much for your reply, and here is another question for me. In the tutorial2, the author embedded the fluxes predicted by scFEA into the scRNA-seq and preserve the sign of the fluxes. I wonder if it possible for me to use the absolute value of fluxes as I just want to focus on the amount of the fluxes as a representation for some metabolic pathways' activity but not the direction.

I guess so. I think the sign does not reflect the direction (if so, I believe the authos should clarify this point), so you can use the absolute value. But you may carefully check the range of the absolute values for specific metabolic pathways, as they may vary too little to represent the difference of metabolic activity across cells or clusters (I note that many flux values are very small), which is visualized by the color of UMAP heatmap. So I recommend you to scale the z-score across cells or samples substituting for absolute values of specific pathways in order to reflect the variation across cells, which might be more readable in the UMAP heatmap.

By the way, maybe the final correct answer should be proposed with the author. I cannot have 100% confidence......

Joyjoyjoyc commented 6 months ago

Really appreciate for your reply!!!

---- Replied Message ---- | From | @.> | | Date | 04/13/2024 11:51 | | To | changwn/scFEA @.> | | Cc | Joyjoyjoyc @.>, Mention @.> | | Subject | Re: [changwn/scFEA] Balance values interpretation (Issue #48) |

@Joyjoyjoyc

Hi, @LiuCanidk, thank you so much for your reply, and here is another question for me. In the tutorial2, the author embedded the fluxes predicted by scFEA into the scRNA-seq and preserve the sign of the fluxes. I wonder if it possible for me to use the absolute value of fluxes as I just want to focus on the amount of the fluxes as a representation for some metabolic pathways' activity but not the direction.

I guess so. I think the sign does not reflect the direction (if so, I believe the authos should clarify this point), so you can use the absolute value. But you may carefully check the range of the absolute values for specific metabolic pathways, as they may vary too little to represent the difference of metabolic activity across cells or clusters (I note that many flux values are very small), which is visualized by the color of UMAP heatmap. So I recommend you to scale the z-score across cells or samples substituting for absolute values of specific pathways in order to reflect the variation across cells, which might be more readable in the UMAP heatmap.

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LiuCanidk commented 6 months ago

@Joyjoyjoyc I found other evidence that the sign may not reflect the flux direction, instead it is an intensity or activity score. As shown below, many pathway consists of the same metabolite, indicating the uptake or secretion of such metabolites, and the direction of uptake or secretion is indicated in the pathway description. E.g., uptake: glucose_in, glutamine_in; secretion: methionine_out image