Evidence map›Paper›PMID 40623818›Full record

ArticleGenome research2025

Batch correction methods used in single-cell RNA sequencing analyses are often poorly calibrated.

Sindri Emmanúel Antonsson, Páll Melsted

Abstract read
In one paragraph

Article in Genome research, 2025. 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.

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  5. Integration of large, complex single-cell datasets with Harmony2.bioRxiv : the preprint server for biology · 2026
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  16. A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025
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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

2 authors.

Sindri Emmanúel AntonssonFaculty of Industrial Engineering, Mechanical Engineering, and Computer Science, University of Iceland, 102 Reykjavík, Iceland.ORCID 0009-0005-0779-6923
Páll MelstedFaculty of Industrial Engineering, Mechanical Engineering, and Computer Science, University of Iceland, 102 Reykjavík, Iceland pmelsted@hi.is.ORCID 0000-0002-8418-6724

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As the number of experiments that employ single-cell RNA sequencing (scRNA-seq) grows, it opens up the possibility of combining results across experiments or processing cells from the same experiment assayed in separate sequencing runs. The gain in the number of cells that can be compared comes at the cost of batch effects that may be present. Several methods have been proposed to combat this for scRNA-seq data sets. We compare eight widely used methods used for batch correction of scRNA-seq data sets. We present a novel approach to measure the degree to which the methods alter the data in the process of batch correction, both at the fine scale, comparing distances between cells, as well as measuring effects observed across clusters of cells. We demonstrate that many of the published methods are poorly calibrated in the sense that the process of correction creates measurable artifacts in the data. In particular, MNN, SCVI, and LIGER perform poorly in our tests, often altering the data considerably. Batch correction with Combat, ComBat-seq, BBKNN, and Seurat introduces artifacts that could be detected in our setup. However, we find that Harmony is the only method that consistently performs well in all the testing methodology we present. Therefore, Harmony is the only method we recommend using when performing batch correction of scRNA-seq data.

Indexed as

RNA-SeqSequence Analysis, RNASingle-Cell AnalysisAlgorithmsArtifactsCalibrationHumans

Identifiers

PMID40623818
PMCPMC12315870

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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.