Reviewer response for version 1
This paper describes the PathLinker Cytoscape app, including the mathematical algorithms and a comparison to similarly-focused Cytoscape apps. 
It is well written and address the important problem of deducing relationships that can advance biology.
It is very economical in its explanation of the app/algorithm, its uses and its relationship to other apps, and in several places needs more explanation. 
Explanations tend to weigh in favor of expert Cytoscape users, though this app would be of interest to less expert users, too, particularly those trying to relate PathLinker to biological investigation. 
The paper would benefit from better enabling the reader to follow a use case in Cytoscape using actual data and actual app settings.
- In Methods | Operation, please explain how to acquire and run PathLinker.
- In "Allow sources and targets in paths" and "Targets are identical to sources", please explain the biological implications of these settings ... 
it's difficult to jump from the graph implications to the biological implications.
- In "Algorithm", why is the default chosen, and what are the biological ramifications of choosing a higher or lower k ?
- The output in Figure 2B seems to be a standalone window. 
How can the user capture the results? 
It's unclear how the user should be using this report in investigating relationships.
- In "Edge penalty", please explain when a edge penalty would be used in a network and what its biological implication would be.
- In "Input datasets and pre-processing", I attempted to download the ToxCost data and could not. 
The site requires a credential and does not give instructions regarding how to get the credential. 
Without this data, the user is hard pressed to reproduce these results and then evolve his/her own questions. 
The web site apparently identifies this data as freely available. 
Can it be included as supplementary material (as a Cytoscape session file?) to assist the user in following this paper?
- In "Input datasets and pre-processing", I tracked down the referenced original PathLinker paper. 
It took a while to determine which network was being used. 
I downloaded it and imported it into Cytoscape. 
During the import, there were a number of options available, and it was unclear which options should be chosen. 
Can this network be included as supplementary material (as a Cytoscape session file?) to assist the user in following this paper?
- In "Running PathLinker", can you explain the biological ramifications behind the k =50 and edge penalty settings?
- In "Further Analysis", can you explain which Cytoscape tool or feature you used to spread the nodes apart? 
I'm thinking of the biological user that's trying to follow the paper.
- In "Functional Enrichment", can you specify which ClueGO settings you used? 
This is a very valuable step, and it's hard for the user to follow without giving settings.
- In "Running Time", how many CPU cores and how much RAM were on the test machine?
- In the "Comparison to related Cytoscape Apps", the discussion focuses on differences in graph analysis approaches, and assumes the reader can appreciate the reasons why PathLinker gives better results. 
The discussion could use a little more justification, and also some grounding in the biological consequences of these differences.
- In the Introduction, the claim "any human signaling pathway" is overbroad. 
I suggest claiming "human signaling pathways".
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