We received the proof to review via the PXE5 system. Here is the PDF proof export: giad047.pdf. Also we can see the changes applied by the copyeditor at giad047-copy-editor-changes.pdf.

The header of the PXE5 system includes:

In case of any difficulty, please contact via US Toll Free: 1.800.767.1518 x 2035 or email: [email protected].

At a first glance, this will need a lot a work, specifically the references where most links to articles have been removed. Also checking carefully what the proof team has changed, I don't see any tracked changes or edit history from the final submission, but haven't looked hard.

Message to Casey (link to open proof removed):

Automated Mailer GIGASCI [email protected]
Date: Wednesday, June 21, 2023 at 9:26 PM
To: Greene, Casey
Cc: [email protected]
Subject: Giga Science: giad047 - Manuscript No. [GIGA-D-23-00005] - check your proof

[External Email - Use Caution]

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Here is the documentation popup about PXE5:

Archiving a copy of Generic_PXE5_UserGuide_Editor.pdf

Manuscript is now published in GigaScience at https://doi.org/10.1093/gigascience/giad047.

Unfortunately the figures that appear in the HTML GigaScience manuscript have two problems:

1. Resolution is too low. For many of our figures that are simple diagrams and plots, use of JPEG instead of PNG encoding exacerbates quality issues.
2. The colors have been changed.

When you click "Open in new tab", you get a higher resolution JPEG (issue 1 is resolved, example), but colors are still off.

I believe the images shown in the HTML manuscript are being generated from the EPS sources we submitted for each figure, but I don't have total clarity on this matter.

Example for Figure 1

Figure 1 is embedded in the manuscript as m_giad047fig1.jpeg with a file size of 45.7 kB (tiny). Here's that figure from the inline HTML view:

And now here's a higher resolution raster version from the Manubot manuscript (screenshot actually, since wanted white background):

Notice the color changes. This is most problematic.

Regarding the resolution, there are obviously benefits to keeping the file sizes small such that the article is fast to load. But I find that the current downsampling is too extreme as the images are unreadable. Also having the break the flow of reading to open a new tab and properly view an image is a poor user experience.

From an 2023-05-17 email to Casey Greene from the GigaScience Editorial Office:

Dear Casey,

Your manuscript "Hetnet connectivity search provides rapid insights into how two biomedical entities are related" (GIGA-D-23-00005R1) is acceptable for publication in GigaScience.

Before we proceed to the production stage, please address the following editorial points:

1. GigaDB citation
   Please include a citation to your new GigaDB dataset (including the DOI link) to your reference list, and cite this by number from the data availability section.

   The citation is:
   [xx] Himmelstein DS, Zietz M, Rubinetti V, Kloster K, Heil BJ, Alquaddoomi F et al. Supporting data for "Hetnet connectivity search provides rapid insights into how two biomedical entities are related" GigaScience Database. 2023. http://dx.doi.org/10.5524/102389

   In the data "availability" section, please write something along the lines, "An archival copy of the code and supporting data is available via the GigaScience repository, GigaDB [xx]".

2. For a technical note, the "availability" section should have the title: "Availability of supporting source code and requirements".

   In this section, list the following:

   Project name: e.g. My bioinformatics project (URL + citation [xx])
   Project home page: e.g. https://github.com/ISA-tools
   Operating system(s): e.g. Platform independent
   Programming language: e.g. Java
   Other requirements: e.g. Java 1.3.1 or higher, Tomcat 4.0 or higher
   License: e.g. GNU GPL, FreeBSD etc.
   RRID: if applicable, e.g. RRID: SCR_014986
   biotools ID: XYZ

   (you can repeat this format if you have several sub-projects)

3. We treat URLs and other internet sources (doi, ftp) as citable items. For each URL/doi (software repo, database, hompage etc) that's mentioned in the text, please create a numbered reference in the bibliography and cite the URL by reference number in the text, rather than using a hyperlink directly. Please refer to our citation guidelines for details.

4. Please structure your abstract (Background, Findings, Conclusions).

5. Please upload the text file in an editable format to Editorial Manager (Word or LaTex).

6. Please also ensure that your revised manuscript conforms to the journal style, which can be found in the Instructions for Authors on the journal homepage

Once you have made the necessary corrections, please submit a revised manuscript online at https://www.editorialmanager.com/giga/

If you have forgotten your username or password please use the "Send Login Details" link to get your login information. For security reasons, your password will be reset.

Thank you for publishing with GigaScience. We look forward to receiving your revised manuscript soon.

Best wishes,
Hans Zauner
GigaScience

I'd like to create a figure for manuscript that shows the webapp functionality at https://het.io/search/.

I took some screenshots for an example workflow, which are available in the repo now.

I was thinking of placing the following images in a 2 by 2 grid:

A. webapp-nodes.png
B. webapp-metapaths.png
C. webapp-paths.png
D. webapp-graph.png

For a grid layout, I like how @vincerubinetti made the Manubot plugins figure. Perhaps we could have a rectangle around each panel to help differentiate them. Also would be good to label each screenshot with an uppercase & bold letter like A. This will help us refer to the panels in the caption and manuscript.

@vincerubinetti would you be able to create this? Or have suggestions for how I should?

The following concepts play a crucial role in this study:

1. metapath instance: referring to a type of path such as Compound–downregulates–Gene–participates–Molecular Function (CdGpMF). This concept is defined a sequence of metaedges.

2. source-metapath-target instance: referring to a type of path between two specific nodes, such as Raltitrexed–downregulates–Gene–participates–histone serine kinase activity. This concept is defined a sequence of metaedges with the a specific source and target node.

3. source-path-target instance: referring to a path between two specific nodes, such as Raltitrexed – downregulates – AURKB – participates – histone serine kinase activity. This concept is defined a sequence of edges.

I think we can refer to 3 as a path, and there won't be confusion because paths are generally understood as traversing specific nodes & edges, hence implying specific source and target nodes.

1 & 2 are more prone to confusion. In 1, we're referring to an abstract type of path, before selecting a specific source and target node. 2 is also a metapath, but now refers to the specific connectivity between two nodes (source and target).

Currently we have a few mentions of related works in the introduction other works section.

The introduction currently describes Hetionet and Rephetio, but doesn't do a great job discussing other studies. It's hard to first figure out what studies are sufficiently related and worthy of mention, especially since terminology varies wildly between disciplines.

@danich1 offered to help, since he's more up to date on the latest literature here.

The top priority is identifying any pre-existing studies on detecting how two nodes are related in a hetnet. If those studies communicate themselves sufficiently and seem to be methodology sound, we should consider them for citation.

Ideally, we can group preexisting studies into sensible categories of how they relate to this work.

@danich1 do you want to take the lead here?

Listing some possible works that we might like to cite for further evaluation.

Currently, the author section looks like:

While the manuscript is still not complete, I think it makes sense to begin adding all coauthors.

@cgreene and I last discussed authorship in June 2020. But from my notes, we had sketched out the following author ordering:

Himmelstein, Zietz, Rubinetti, Kloster, Heil, Hu, Nicholson, Hao, Sullivan, Nagle, Greene

A few notes:

• this order is of course preliminary as the manuscript is not complete
• we will reorder authors as warranted by additional contributions
• let us know if we could be forgetting someone
• from the greenelab onboarding

  Our lab follows the Perelman School of Medicine Authorship Policy. These guidelines are derived from ICMJE's Uniform Requirements for Manuscripts Submitted to Biomedical Journals."

• we feel everyone listed above meets the criteria for authorship. But if for any reason someone would not like to be a coauthor, let us know either here or privately.
• we'll notify everyone when the manuscript is complete, by commenting on this issue or elsewhere, before making the initial release (e.g. preprint or journal submission).

In the next comment, I will tag people and provide instructions for adding yourself as a coauthor.

Currently, the "Webapp & Frontend" section is just a placeholder. I was thinking this section could describe some the technical aspects of

• https://het.io/search/
• https://github.com/greenelab/connectivity-search-frontend

I envision a couple of paragraphs that describe which frameworks we use and any major contributions or novel aspects of the frontend. The Backend Database & API methods section might be a helpful example here.

@vincerubinetti would you be able to draft a couple paragraphs here or provide a list of things we should mention?

refs #52

It appears that Gigascience uses JPG for all images in the web version, but can use EPS to include vector images in the PDF. Therefore in pursuit of a pretty PDF, we should submit EPS files for all figures where the source exists in a vector format.

Currently the manuscript has the following figure and caption for the project rephetio ML approach:

I think we can make this fit the connectivity search aesthetic a bit better. I've made some improvements at https://slides.com/dhimmel/rocky2019#/11/1/3:

The additions are as follows:

• axis labels
• dashed divider for treatments/non-treatments, and better labeling of treatments
• changing the metapath to use the connectivity search encircled abbreviation format

other ideas:

• compound-disease pairs can use connectivity search background highlights
  Like but the edge has no label because these are just endpoints.
• remove status column if treatment/non-treatment is clear from other visual element

The SVG source is available here. @vincerubinetti how doable do you think these changes are?

Also thinking of making this a 1x2 figure where A is the new metagraph with new node colors created for connectivity search (after hetio/het.io#36 is fixed). B would be the rephetio feature heatmap above.

From Hans Zauner on 2023-02-20:

Two editorial notes:

1. Please register any new software application in the bio.tools and SciCrunch.org databases to receive RRID (Research Resource Identification Initiative ID) and biotoolsID identifiers, and include these in your manuscript. Computational workflows should be registered in workflowhub.eu and the DOIs cited in the relevant places in the manuscript. These will facilitate tracking, reproducibility and re-use of your tool.

2. If you refer to repositories, software sites or other online data sources (URLs or dois) in the text, please add a numbered reference for the doi/URL to the bibliography and cite it from the main text by reference number, rather than adding the hyperlink directly (exception: if you refer to several sub-directories of the same repo, it's enough to include the main URL once in the bibliography). Please refer to our citation guidelines for details.