No growth with CarveMe v.1.5.0

[lumlukwp]

Hi Daniel,

I built the model like so carve protein.faa —init M9 -u gramneg —cobra -o model.xml.
The model I built with v1.2.1 was able to grow on M9 media but the one with v1.5.0 does not.
Do you have any suggestions?

Thank you in advance for your help.

[cdanielmachado]

I think this issue is related to this one: cdanielmachado/reframed#2

Can you gap-fill explicitly for M9 and check how many gap-filling reactions are added?

carve protein.faa -g M9 -i M9 -u gramneg —cobra -o model.xml -v

[lumlukwp]

The models were able to predict growth using the gap-filling approach with only few reactions added. However, the growth rate is quite low compare to the previous version. The numbers are found below:

Model	GrowthRate	#Reactions	#Metabolites	#Genes
m9 v1.2.1	0.769926383	2151	1447	1330
m9 v1.5.0	0	2442	1615	1497
m9_gapfill v.1.5.0	0.186136468	2448	1616	1497
LB v1.2.1	2.181619235	2151	1447	1330
LB v1.5.0	0	2442	1615	1497
LB_gapfill v1.5.0	0.370916621	2446	1616	1497

What version should I continue with?

[silvtal]

I have similar results. As I said, the media I was using was M9 (with glucose):

Model	Growth	Reactions	Added
CarveMe 1.4.1	0.796	2296	-
CarveMe 1.5.0	0.0	2468	-
CarveMe 1.5.0 gapfilled	0.120	2471	R_BZDH, R_LO, R_PHPYROX

The 1.5.0 model has 172 more reactions, but when I try a for reactions in cm_150 not in cm_140 it returns 1099 reactions. There are also 927 reactions in the old model that are not in the new one, apparently.

Loading the models with flavor="bigg" returns the same values.

[cdanielmachado]

Thank you both for helping me understand the problem.

• Very few gap-filling reactions are added in all cases, this is good. Like I said, without explicitly gap-filling for M9, it is mostly a matter of "luck" if the models will grow on M9 out-of-the-box.

• The growth rates are much lower, this doesn't sound so good. Can you send me your fasta files for these models, so I can try to see what is going on?

[silvtal]

Sure. It's from GTDB v95. You can download it here https://gofile.io/d/4teCZ9

[cdanielmachado]

Thanks a lot. I will try to understand what has changed so drastically.

Please feel free to report any other differences that you find between the two versions. Especially differences in phenotype simulation.

[cdanielmachado]

Should be solved in release 1.5.1, otherwise please re-open this issue.