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Add malignant cells results section#234

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sjspielman merged 13 commits intomainfrom
sjspielman/214-malignancy-results-section
Jan 13, 2026
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Add malignant cells results section#234
sjspielman merged 13 commits intomainfrom
sjspielman/214-malignancy-results-section

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@sjspielman sjspielman commented Jan 12, 2026

Closes #214

This PR adds a (kind of hefty, but words can definitely be cut once we nail down the full content scope in review!) new section detailing the malignancy bits: limitations of consensus, openscpca annotations, and inferCNV. I structured text to follow the order of the figure 5 panels (for reference, here is figure 5) to introduce openscpca first, then infercnv, and finally how cnv + consensus can be used as a proxy to ID malignant cells. I think this flow is probably fine, but I also see a world where it's a bit funky and might slightly benefit from switching the panels 5A <-> 5B to be able to introduce inferCNV (a step embedded in scpca-nf) before OpenScPCA (a step external to scpca-nf). This would result in a bit of text reorganization here, but I don't think that change is crucial. That repo is ready for release, but in case anyone wants to advocate hard for swapping that order I'm holding off on cutting the release just a smidge.

A couple spots in particular to note:

  • What do you think of the section title I came up with?
  • I included a little calculation in there to emphasize the benefits of openscpca annotations having way more labeled cells. I put the calculation inside an html comment with a TODO - do we want to include these values in the manuscript-numbers folder in scpca-paper-figures? Again, that repo is otherwise ready for release, but can add this in first if preferred.
  • The last paragraph includes text that interprets Fig S4C, but it didn't seem strictly necessary to me to move the existing text we have for 4A-B. Let me know if you think integrating that existing text into this new section would be better.
  • As noted, this new section is already a bit long, so I tried not to go too in depth for interpretations of figures, which also leaves room for readers to do more of the science, not us! Let me know if you prefer more/less depth.

Just to summarize from the above, these are the questions for reviewer(s) that relate to scpca-paper-figures:

  • do we still like the figure 5 A/B panel ordering, considering the associated flow of the text?
  • do we want to formally add to manuscript-numbers? i think that mostly depends if that sentence survives review!

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Since there's quite a bit of new text here, I'm going to request @jaclyn-taroni for primary review (with the understanding that it might take a minute to get to, which seems fine, we're on a good schedule here!).

But, @allyhawkins if you also want to weigh in, in general or in particular on the questions about scpca-paper-figures I raised in the opening comment, please feel free!

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I think the overall organization is good and I like talking about OpenScPCA first because then you can say that the inferCNV results match up with expectations based on OpenScPCA annotations. Because of that I would keep the figure order.

In parallel to developing the ScPCA Portal, we launched the OpenScPCA project [@url: https://openscpca.readthedocs.io], an open-science collaborative initiative to further characterize and analyze Portal data.
As part of this project, we have thus far performed manual cell type annotations on two projects, `SCPCP000004` (neuroblastoma) and `SCPCP000015` (Ewing sarcoma), and made the associated annotations available in the Portal for broad reuse.
Figure {@fig:fig5}A displays, for example, a UMAP of all libraries in `SCPCP000004` highlighting this project's OpenScPCA annotations.
These annotations were derived based on the `NBAtlas` reference [@doi:10.1016/j.celrep.2024.114804] using both `SingleR` and `scArches` [@doi:10.15252/msb.20209620; @doi:10.1038/s41587-021-01001-7], leveraging consensus cell type annotations to resolve differences between these methods; more information about the specific annotation procedure can be found in the `OpenScPCA-nf` GitHub repository at <https://github.com/AlexsLemonade/OpenScPCA-nf/tree/main/modules/cell-type-neuroblastoma-04>. <!-- TODO: Is this link overkill and adding too much text? We do link OpenScPCA-nf repo in Methods -->
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If we are trying to keep things concise and shorter, then I agree that this is too much and we don't need to link it.

These annotations were derived based on the `NBAtlas` reference [@doi:10.1016/j.celrep.2024.114804] using both `SingleR` and `scArches` [@doi:10.15252/msb.20209620; @doi:10.1038/s41587-021-01001-7], leveraging consensus cell type annotations to resolve differences between these methods; more information about the specific annotation procedure can be found in the `OpenScPCA-nf` GitHub repository at <https://github.com/AlexsLemonade/OpenScPCA-nf/tree/main/modules/cell-type-neuroblastoma-04>. <!-- TODO: Is this link overkill and adding too much text? We do link OpenScPCA-nf repo in Methods -->
Unlike the consensus cell type annotations, the OpenScPCA project annotations distinguish between normal and malignant cells and contain far fewer uncharacterized cells.
Indeed, for `SCPCP000004`, the consensus cell type procedure labeled only ~43% of cells, but the OpenScPCA project labeled ~91% of cells, thereby adding substantial value to the data.
<!-- Calculation. TODO: Do we want this added to `scpca-paper-figures` manuscript-numbers folder?
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I like having this number so I would say yes to this question.

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I think the overall organization is good and I like talking about OpenScPCA first because then you can say that the inferCNV results match up with expectations based on OpenScPCA annotations. Because of that I would keep the figure order.

Thanks for having a look, @allyhawkins! Noting that in my 1:1 with Jackie just now, we also agreed to keep the figure order so that's all set! I will be adding in a quick addition to manuscript-numbers next door though.

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A couple comments, but I don't need to see this again

Co-authored-by: Jaclyn Taroni <19534205+jaclyn-taroni@users.noreply.github.com>
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@sjspielman sjspielman merged commit 7e4d905 into main Jan 13, 2026
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@sjspielman sjspielman deleted the sjspielman/214-malignancy-results-section branch January 13, 2026 14:02
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Add new "Adding malignancy-specific information" section to "Annotating cell types" results section

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