Research method
Single-cell QC (mitochondrial filtering)
Single-cell QC decides which barcodes/nuclei enter analysis—classic filters (including high mitochondrial content) remove damaged cells but can also discard biologically real stressed or metabolically altered states.
Pipelines look objective. Filtering choices change who is in the atlas—especially for disease or perturbation studies—and foundation models inherit those choices.
Evidence
What the evidence shows
Drawn from 3 studies in this library. Each finding starts with a plain-language takeaway, then the denser detail. Supports means evidence for a finding; Challenges means evidence against a stated position; Qualifies marks scope with a short note on each study’s contribution. Challenged positions are labeled — they are not findings.
High-mito filters can deplete viable metabolically altered malignant cells.
Filtering cells with high mitochondrial content is shown to remove not only debris but also viable metabolically altered malignant cells—QC as biology, not just cleanup.
Foundation cell models for post-perturbation prediction need careful benchmarks.
Benchmarking foundation cell models for post-perturbation RNA-seq prediction tests how well learned representations generalize after QC and perturbation—downstream of filtering choices.
- High-mito filters can discard living cancer cell states— model benchmark ≠ mito-filter depletion experiment
Disease atlases depend on QC’d nuclei before cell-state claims.
ICM snRNA-seq profiles ~100k QC’d cardiac nuclei before composition claims—reminding students that atlas biology sits atop filtering decisions.
- High-mito filters can discard living cancer cell states— heart atlas composition ≠ mito-filter methods paper
Open questions
Tensions and limits
Some items are genuine disagreements on the same question. Others mark different assays, populations, or outcomes — limits on how far one study travels — not a forced fight between papers.
A mito-filter methods result, a foundation-model benchmark, and a disease atlas answer different layers of the single-cell stack.
Common misconceptions
High mitochondrial reads always mean the cell is dead junk.
Some viable, metabolically altered states also score high and can be discarded by blunt filters.
Exam-style questions
Short-answer questions that ask you to explain or compare, not recall.
What risk does a blunt high-mito filter carry beyond removing debris?
It can deplete viable metabolically altered cells that matter biologically.
The studies
3 studies in this library bear on Single-cell QC (mitochondrial filtering), ordered by citations.
- What cell programs mark ischemic cardiomyopathy?
snRNA-seq of ~100k cardiac nuclei showed fewer cardiomyocytes and more specialized endothelial states in ICM, overlapping other end-stage cardiomyopathy programs.
- High-mito filters can discard living cancer cell states
Across ~441k cells from 134 patients, malignant cells often exceed 15% mitochondrial RNA without stress-death signatures and show metabolic programs relevant to therapy.
- Simple baselines beat cell foundation models on Perturb-seq
Benchmarking scGPT and scFoundation against baselines finds that training-set mean and basic ML with biological features outperform the foundation models on post-perturbation expression prediction.
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