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feat(archetype): add archetype projection - #4412
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…ation, and cleanup
Removed unnecessary comment prefix and updated baseline generation info.
Co-authored-by: Corey Weistuch <WeistucC@mskcc.org> Co-authored-by: Charles Kocher <charlesdkocher@gmail.com>
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All core test suites and the benchmark pipeline are passing green! The code is synced with main. Note: The PR validation check (title/labels) and the Read the Docs build are currently failing. I’d appreciate a maintainer’s guidance or assistance with those when reviewing. Ready for review whenever you have a chance! |
@ivirshup Friendly ping on this! All test suites and benchmark jobs are passing green. Whenever you have a moment to take a look or help assign the release milestone, I'd really appreciate your review. Thanks! |
This package provides a system for scoring phenotypic states of single-cell data using archetypal analysis. The input is a single-cell gene expression matrix, which is transformed using a pre-trained weighting matrix and scaling matrix to identify representative phenotypic states based on gene expression. The output is a set of archetype representations and corresponding archetype projections for each cell, stored in the AnnData object.
Biological validation:
We applied this archetypal method to single-cell RNA sequencing data from breast cancer primary tumors and brain metastases, based on the dataset described by Yan, Y., Lin, Y., Kumar, T., et al. Ecotypes of triple-negative breast cancer in response to chemotherapy. Nature 654, 1088–1097 (2026). https://doi.org/10.1038/s41586-026-10469-9. The resulting archetype projections were used to identify differences in transcriptional phenotypes associated with response to chemotherapy. In particular, the proliferation archetype showed significantly greater activity in tumors from patients who achieved pathological complete response (pCR) after chemotherapy than in patients with residual disease (RD; p = 0.0026), supporting the archetypal method's ability to recover biologically meaningful tumor-state differences.
This work was developed with guidance from Corey Weistuch, Charles Kocher, and Saurish Arora at Memorial Sloan Kettering Cancer Center.