Evidence map›Paper›PMID 35743881›Full record

ArticleLife (Basel, Switzerland)2022

Recommendations of scRNA-seq Differential Gene Expression Analysis Based on Comprehensive Benchmarking.

Jake Gagnon, Lira Pi, Matthew Ryals, Qingwen Wan, Wenxing Hu, Zhengyu Ouyang, Baohong Zhang, Kejie Li

Abstract read
In one paragraph

Article in Life (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

  1. Trial
  2. 4-1BBCell reports. Medicine · 2025
    Trial
  3. Article
  4. Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Jake GagnonAnalytics and Data Sciences, Biogen, Inc., 225 Binney St., Cambridge, MA 02142, USA.
Lira PiPharmaLex, 1700 District Ave., Burlington, MA 01803, USA.
Matthew RyalsPharmaLex, 1700 District Ave., Burlington, MA 01803, USA.
Qingwen WanPharmaLex, 1700 District Ave., Burlington, MA 01803, USA.
Wenxing HuResearch Department, Biogen, Inc., 225 Binney St., Cambridge, MA 02142, USA.
Zhengyu OuyangBioInfoRx, Inc., 510 Charmany Dr., Suite 275A, Madison, WI 53719, USA.
Baohong ZhangResearch Department, Biogen, Inc., 225 Binney St., Cambridge, MA 02142, USA.
Kejie LiResearch Department, Biogen, Inc., 225 Binney St., Cambridge, MA 02142, USA.ORCID 0000-0003-2134-3857

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To guide analysts to select the right tool and parameters in differential gene expression analyses of single-cell RNA sequencing (scRNA-seq) data, we developed a novel simulator that recapitulates the data characteristics of real scRNA-seq datasets while accounting for all the relevant sources of variation in a multi-subject, multi-condition scRNA-seq experiment: the cell-to-cell variation within a subject, the variation across subjects, the variability across cell types, the mean/variance relationship of gene expression across genes, library size effects, group effects, and covariate effects. By applying it to benchmark 12 differential gene expression analysis methods (including cell-level and pseudo-bulk methods) on simulated multi-condition, multi-subject data of the 10x Genomics platform, we demonstrated that methods originating from the negative binomial mixed model such as glmmTMB and NEBULA-HL outperformed other methods. Utilizing NEBULA-HL in a statistical analysis pipeline for single-cell analysis will enable scientists to better understand the cell-type-specific transcriptomic response to disease or treatment effects and to discover new drug targets. Further, application to two real datasets showed the outperformance of our differential expression (DE) pipeline, with unified findings of differentially expressed genes (DEG) and a pseudo-time trajectory transcriptomic result. In the end, we made recommendations for filtering strategies of cells and genes based on simulation results to achieve optimal experimental goals.

Indexed as

benchmarkingDEDEGdifferential expressionRNA-seqscRNA-seqscRNA-seq simulatorsingle-cell

Identifiers

PMID35743881
PMCPMC9225332

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.