Update media definitions, document and extend db

[famosab]

I will collect the ToDos from this thread here @GwennyGit maybe you can mark what you did already and on what branch :D

• remove CGXII and replace by CGXlab but rename to CGXII
• remove LB and M9 without oxygen
• write function to simulate without oxygen Add boolean to enable anaerobic growth simulation to all relevant functions

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• Re-evaluate all media in database:
  • LB [7][11]
  • M9 [6]
  • CGXII [4]
  • SNM3 [1]
  • SMM
  • RPMI [3]
  • CasA [5]
  • Blood [9]
  • Urine MP-AU [10]
• document all available media in the documentation
  • Create RST file(s) for the media definitions
  • LB [7]
  • M9 [6]
  • CGXII [4]
  • SNM3 [1]
  • SMM
  • RPMI [3]
  • CasA [5]
  • Blood [9] -> $\textcolor{red}{\text{Check where the Blood medium came from originally again!}}$
  • Urine MP-AU [10]
  • dGMM [8]
  • SLM [12] -> Artificial Sebum, Sweat & Basal medium belong to it!
  • TSB
• Document all available subsets in the documentation
  • Create RST file(s) for the subset definitions
  • CasA
  • protAA
  • artSe
• Add page 'How to obtain an in sillico medium from a laboratory medium' to documentation
• Add Blood [2] [9]
• Add Urine [2] Add MP-AU [10]
• Add defined gut microbiota medium (dGMM) [8]
• Add SLM components [12]:
  • Add Artificial Sweat to medium
  • Add Artificial Sebum to subset
  • Add Basal medium (Name from paper, Renamed to: BMS23 for Basal Medium Swaney 2023)

---

• Add compound names to:
  • RPMI
  • SNM3
• Add subsets:
  • CasA - Contains only Casamino acids
  • AA - Contains all proteinogenic amino acids
  • DiReM - Metabolites for the dissipation reactions
    • already in: 'Water [H2O]', 'ATP [Adenosine triphosphate]','ADP','Hydrogen [H(+)]','Phosphate [PO4(3-)]',
      'CDP','GTP [Guanosine triphosphate]', 'GDP [Guanosine diphosphate]', 'UDP [Uridine 5-diphosphate]',
      'Nicotinamide adenine dinucleotide [NAD]', 'Nicotinamide adenine dinucleotide phosphate [NADP]',
      'Flavin adenine dinucleotide oxidized [FAD]', 'FMN [Flavin Mononucleotide]', 'D-Glucose',
      '2-Oxoglutarate [Oxoglutaric acid]', 'Ammonia'
    • missing:
      • CTP
      • UTP
      • ITP
      • IDP
      • NADH
      • NADPH
      • FADH2
      • FMNH2
      • Q8H2
      • Q8
      • MQL8
      • MQN8
      • 2DMMQL8
      • 2DMMQ8
      • ACCOA
      • AC
      • CoA
      • DUPLICATE: Acetate and Acetate [Acetic acid] : remove the former + replace in subset, ....
    • 🔴 NOTE: these reactions are all about proton exchange, might lead to problems, since we usually ignore difference in protons .... in these cases it might be important to watch out for them - maybe also use this as a set to skip during duplicate removal, as this also includes protons differences
• Check in generate_insert_query for strings in value_string❗

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Feature request for maintenance

• Add function to update tables/specific table entries automatically

---

• More database identifiers -> Check BiGG+VMH overlaps
• Add superoxide ❗
• Add a definition for Tryptic Soy broth (TSB)
• Add a definition for Brain Heart Infusion (BHI)

---

[1]
Krismer, Bernhard; Liebeke, Manuel; Janek, Daniela; Nega, Mulugeta; Rautenberg, Maren; Hornig, Gabriele et al. (2014): Nutrient Limitation Governs Staphylococcus aureus Metabolism and Niche Adaptation in the Human Nose. In: PLOS Pathogens 10 (1), e1003862. DOI: 10.1371/journal.ppat.1003862.
[2]
Ding T, Case KA, Omolo MA, Reiland HA, Metz ZP, Diao X, Baumler DJ. Predicting Essential Metabolic Genome Content of Niche-Specific Enterobacterial Human Pathogens during Simulation of Host Environments. PLoS One. 2016 Feb 17;11(2):e0149423. doi: 10.1371/journal.pone.0149423. PMID: 26885654; PMCID: PMC4757543.
[3]
https://www.thermofisher.com/de/de/home/technical-resources/media-formulation.114.html
[4]
Unthan, Simon, et al. "Beyond growth rate 0.6: What drives Corynebacterium glutamicum to higher growth rates in defined medium." Biotechnology and bioengineering 111.2 (2014): 359-371., Preparation protocol
[5]
Richard A. Nolan (1971) Amino Acids and Growth Factors in Vitamin-Free Casamino Acids, Mycologia, 63:6, 1231-1234, DOI: 10.1080/00275514.1971.12019223
[6]
https://www.sigmaaldrich.com/DE/de/product/sigma/m6030, Preparation protocol
[7]
Machado, Daniel, et al. "Fast automated reconstruction of genome-scale metabolic models for microbial species and communities." Nucleic acids research 46.15 (2018): 7542-7553.
https://carveme.readthedocs.io/en/latest/advanced.html#media-database
[8]
Tramontano, M., Andrejev, S., Pruteanu, M. et al. Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. Nat Microbiol 3, 514–522 (2018). https://doi.org/10.1038/s41564-018-0123-9
[9]
Nantia Leonidou, Alina Renz, Reihaneh Mostolizadeh, and Andreas Dräger. New workflow predicts drug targets against sars-cov-2 via metabolic changes in infected cells. PLOS Computational Biology, 19(3):1–32, 03 2023. URL: https://doi.org/10.1371/journal.pcbi.1010903, doi:10.1371/journal.pcbi.1010903.
[10]
Sarigul, N., Korkmaz, F. & Kurultak, İ. A New Artificial Urine Protocol to Better Imitate Human Urine. Sci Rep 9, 20159 (2019). https://doi.org/10.1038/s41598-019-56693-4
[11]
Oh, Y. K., Palsson, B. O., Park, S. M., Schilling, C. H., & Mahadevan, R. (2007). Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. Journal of Biological Chemistry, 282(39), 28791-28799. https://doi.org/10.1074/jbc.M703759200
[12]
Swaney MH, Nelsen A, Sandstrom S, Kalan LR. Sweat and Sebum Preferences of the Human Skin Microbiota. Microbiol Spectr. 2023 Feb 14;11(1):e0418022. doi: 10.1128/spectrum.04180-22. Epub 2023 Jan 5. PMID: 36602383; PMCID: PMC9927561

[famosab]

I added Casamino Acids to the media definition based on an article from 1971 - Amino Acids and Growth Factors in Vitamin-Free Casamino Acids.

[famosab]

@GwennyGit maybe you can add the gut medium as soon as you get to that. But we might rethink how we note the media definitions. At the moment it is just a big csv file which works but entering it into the database we use for sboann might be more elegant?

[GwennyGit]

The idea of using the database sounds good. However, if someone would want to use the media definitions in another program like for example the gapfill function of CarveMe it is easier to transform the CSV file into the required format. Additionally, it might be easier to use the CSV file to add other media if the user wants to. @famosab What do you think? 🤔

[famosab]

I think we should move the existing media definitions into the database as well. You mentioned somewhere that access via pandas should be possible. If that works for a user that just installs refineGEMs via pip, it would be great! Maybe we can implement a function which exports the database entries to a csv medium definition. The functionality for a possible user would still be the same since they could just use a local csv as well.

[GwennyGit]

Yes, I mentioned that in issue #49, and I am currently working on that task.

[famosab]

At the moment we have both CGXII and CGXIlab in the database. I would advise to remove CGXII and replace it by the composition of CGXlab since that is the composition which is used in for the manuscript we will publish soon and CGXII is just a file I got a while ago but is not verfiied with laboratory use. We could also remove LB and M9 without oxygen or write a small function to allow for anaerobic simulation on any of the media.

[GwennyGit]

Removing CGXII and only keeping CGXlab of these two media is a good idea. However, I think it would also be good to describe all media in the documentation so that the user knows what it is, why the user could use which and so on.

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Yeah, creating a small function to allow for anaerobic simulation on any media sounds like a great idea. Then this simulation part would not only be restricted to M9 and LB.

[GwennyGit]

I created so far only the basic set-up for the media definition pages. Thus the pages still need to be filled with content.

[GwennyGit]

Re-evaluation of SNM3
The composition of SNM3 within refineGEMs was compared to another composition used within the draeger-lab group as well as to the original wet lab composition described in 'Nutrient Limitation Governs Staphylococcus aureus Metabolism and Niche Adaptation in the Human Nose' [1]. Additionally, all compound assignments to the BiGG database were checked and the names added with the following pattern: BiGG ID [Name in wet lab description].

From the comparison the following differences were found:

1. For Cyanocobalamine which is Vitamin B12 the SNM3 definition in refineGEMs listed adocbl which is the BiGG ID for Adenosylcobalamine. As the chemical formula is no good match for Cyanocobalamine this compound was removed from the definition.
   -> Replaced adocbl with cbl1 (Cob(I)alamine), cbl2 (Cob(II)alamine and b12 (Vitamin B12). The first two BiGG IDs were chosen due to having a high similarity to the chemical formula of Cyanocobalamine and being already included in the SNM3 definition from the draeger-lab group. b12 was added as Cyanocobalamine is Vitamin B12.
2. In the draeger-lab group both fe2 and fe3 are contained in the SNM3 definition. However, the refineGEMs definition only contained fe2. Thus, fe3 was added.

In conclusion after discussing with @famosab we decided to add all analoga for each compound for all media. Hence, the addition of all possible similar compounds to Cyanocobalamine and Iron (Fe).

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[1]
Krismer, Bernhard; Liebeke, Manuel; Janek, Daniela; Nega, Mulugeta; Rautenberg, Maren; Hornig, Gabriele et al. (2014): Nutrient Limitation Governs Staphylococcus aureus Metabolism and Niche Adaptation in the Human Nose. In: PLOS Pathogens 10 (1), e1003862. DOI: 10.1371/journal.ppat.1003862.

[famosab]

Re-evaluation of RPMI
The composition of the in silico RPMI medium was compared to the provider reference. This comparison yielded the following points:

• tyr__L is chosen for L-Tyrosine disodium salt dihydrate
• inost is Myo-Inositol but RPMI contains I-Inositol, these two are different but since there is no BiGG Id for I-Inositol yet it was left inside
• hco3 was added since Sodium Bicarbonate is contained
• 4hpro_LT was added since L-Hydroxyproline is contained
• b12 was added for Vitamin B12, cbl1 was kept and clb1 was removed since it is not a correct BiGG Id
• nac was removed since the medium does only contain Niacinamide which is covered by ncam
• Phenol Red has not BiGG Id so far, the corresponding KEGG Id is C12600, it was added without BiGG Id
• h was added since L-Cysteine HCl is contained

[famosab]

Re-evaluation of M9

The M9 composition is based on the provider reference for the minimal salts:

• KH2PO4: k, h, pi
• NaCl: na1, cl
• Na2HPO4: na1, h, pi
• NH4Cl: nh4, cl

Plus necessary additives as described here and here:

• MgSO4: mg2, so4
• CaCl2: ca2, cl
• Glucose: glc__D

And o2 and h2o are present per standard.

[GwennyGit]

Addition of the defined Gut Microbiota Medium (dGMM) to the database
To get all relevant BiGG IDs for the salts the following table was used:

Ion	Abundance	BiGG ID	BiGG name
Fe(II)	1	fe2	Fe2+
SO4	6	so4	Sulfate
Zn	1	zn2	Zinc
Co	1	cobalt2	Co2+
NO3	1	no3	Nitrate
Al	1	-	-
K	2	k	Potassium
Na	5	na1	Sodium
SeO3	1	slnt	Selenite
WO4	1	tungs	Tungstate
Ni	1	ni2	Nickel
Cl	3	cl	Chloride
Ca	1	ca2	Calcium
Cu	1	cu2	Copper
Mn	1	mn2	Manganese
Mg	1	mg2	Magnesium
HCO3	1	hco3	Bicarbonate
MoO4	1	mobd	Molybdate
H	1	h	Hydrogen
PO4	1	pi	Phosphate

Additionally, water was added to the definition as most salts were added with water in the laboratory version of GMM. For Resazurin, boric acid (H3BO3), Aluminium (Al), dihydrogen phosphate (H2PO4) and EDTA no BiGG IDs were found. However, dihydrogen phosphate could be separated into hydrogen (H) and phosphate (PO4) for which BiGG IDs exist. This was changed in commit (Needs to be committed❗).

[cb-Hades]

Database restructuring finished, namespace issues moved to #36 and ideas for new media have been added to #123