Hello,
The following article https://www.nature.com/articles/s41598-018-26689-7#Sec28 under the section Methods subsection Pathogen-specific pathways explains how the researches identified proteins only present in pathogen pathways. I am quite confused about the methodology here. Apparently, they listed the pathways of the non-homologous proteins of the pathogen and also the pathways of the host (Homo sapiens) by K number. Then, they compared the two lists to find what pathways are common and unique. In the results section subsection Involvement of selected A. baumannii proteins in the unique and common pathway, they explain that they found 33 unique pathways and 104 common pathways. The 33 unique pathways contained 126 proteins and, out of these, 34 proteins play a role in unique pathways and 92 have a role in both unique and common pathways. Finally, they used the 34 proteins to proceed the analysis.
I understand the purpose of the employed method, no questions about that. My doubt is relative to the efficiency of it as I'd like to adopt a similar approach. When I ran my own data against KEGG PATHWAY and chose to classify the results by K number the results were different compared to when I chose to run against the specific organism (org). Doesn't is mean that we could be potentially ignoring a few pathogen proteins involved in pathways? Also, wouldn't it be easier if we first analyze the non-homologous proteins from the pathogen against the KEGG PATHWAY, identify the proteins that play a role in metabolic pathways, and finally use the comprised list of pathogen proteins involved in pathways to compare the pathways of the pathogen and the host?
Finally, even if proteins from the pathogen and host are involved in the same pathway, would it still be relevant to compare the two organisms pathways and exclude the common pathways since the proteins are non-homologous? Say they develop the vaccine against A. baumannii and the protein target is one involved in a common pathway, since they are non-homologous would that still impact, in any way, the host?
By no means I want to negatively criticize the work of the authors. My intention here is purely focused on my doubts about the methodology and the way we should conduct it. Thank you.
