Reviewer response for version 1
The article "Cluster analysis of Plasmodium RNA-seq data identifies stage-specific co-regulated biological processes and regulatory elements" uses an RNA-seq dataset published in Otto et al. 1 for a number of Plasmodium species. 
Authors use the assumption that co-transcribed genes are likely to be controlled by a common regulatory element. 
Subsequently they provide a clustering of expression profiles using that dataset.
I would propose the following enhancements to the article:
- In order to ensure the reproducibility of the experiment, I would request if more information could be provided about the raw dataset from which the study has derived. 
Things like number of samples, what conditions, how big the data is, etc. 
This information should be available in the source paper.
- What parameters did you use to run maSigPro? 
What parameters did you use to cluster gene expression patterns?
- I am concerned about the use of Herrero et al.'s tool, which was published in 2001. 
This tool was developed for array data, a long time before NGS data like transcriptomics became available.
- In results: 155 genes out of 1448 is not ~0.1%. 
It's ~10%.
- In table 2, I am not sure what the background percentages are. 
I would appreciate if legends made figures self explanatory.
- When presenting results, for each section there is a lot of background information. 
For example: Section 1: "Characterized genes may provide alternative sources for drug targets of the IDC". 
I find this header too obvious and uninformative. 
The text at the beginning of this section up to the sentence "For the ICD, to clusters [...]" is all material that would be better placed in a discussion section. 
Clearly this text is not part of what I would call "results". 
I find the other sections within Results also have a lot of preliminary background information that in my opinion would be more suitable for a discussion section than results. 
Another example is the section "Sustains up-regulated [...]". 
I still think this background information is necessary though to understand the context of results.
- I would find it helpful if Figure 3 was referenced from the text in the relevant section. 
Currently, as it appears in the paper, I had no idea why of how it related to the paper until I read the section "Sustained up-regulated biological processes linked to invasion may present key drug targets to prevent transmission".
- In conclusions I don’t understand this sentence: 
“We showed that each development stage activated biological process custom to the anticipated environment unique to each development stage in which we identified 14 biological processes that may be integral at different stages of the parasites development, 11 of which have not been investigated in drug-related research."
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