Question about XomicsToModel field, inactiveGenesTranscriptomics

[Dana Luong]

Hello, happy holidays and happy new year!

I have a conceptual question about XomicsToModel, and was not able to find an answer in the paper. What is the purpose of the inactiveGenesTranscriptomics field and the removeInactiveGenes block? Why do we need to specify inactiveGenes if there exists a field that tracks the activeGenes (those whose expression falls above the global threshold)? And why does the removeInactiveGenes block come before flux consistency? 

During one of my Xomics runs, the model was not able to carry flux through the cardiolipin biosynthetic reaction CLS_hs after the removeInactiveGenes step when set as the objective, though the expression of the associated gene was above the threshold. In this run, cardiolipin, CLS_hs, and biomass were pruned during flux consistency. I was not able to identify which exact gene and reaction upstream of CLS_hs caused the block (any suggestions on how to do so could also be helpful!) When the inactiveGenesTranscriptomics was set to false, skipping the entire block at line 1540, flux consistency passes and the output models carry biomass. Do you have any ideas on what may be happening or how to investigate this further?

Thank you!

Best,

Dana 

[Hoang Dinh]

I am not familiar with the method you mentioned, but I am assuming you want to do context-specific model reconstruction. A reaction above the threshold might not be extracted because for reaction to carry flux other reactions up and downstream have to also be active. If your reaction (CLS_hs) in this case is not added, this means that the minimal pathway to allow flux through this reaction is below threshold on average across pathway reactions.