# OTMODE: an optimal transport theory-based framework for identifying differential features in single-cell multi-omics data

**Authors:** Huidong Su, Caicai Zhang, Frank Qingyun Wang, Chun Hing She, Xinxin Chen, Xiao Dang, Yao Lei, Ke Ni, Zewei Xiong, Danqing Yin, Xingtian Yang, Hong Feng, Philip H Li, Wanling Yang

PMC · DOI: 10.1093/bioinformatics/btaf650 · Bioinformatics · 2025-12-03

## TL;DR

OTMODE is a new method that improves the identification of important features in complex single-cell multi-omics data using optimal transport theory.

## Contribution

OTMODE introduces a non-parametric framework using unbalanced Sinkhorn algorithm and Wald test for differential feature identification.

## Key findings

- OTMODE achieved an average 90% F1 score and 92% AUC score in simulations.
- It outperforms existing methods in detecting meaningful biological processes.
- OTMODE can identify potentially misannotated clusters from auto-annotation tools.

## Abstract

Single-cell technologies enable high-resolution cellular studies but face challenges in identifying differential features due to data complexity.

We present OTMODE, a non-parametric method using unbalanced Sinkhorn algorithm and Wald test to improve differential feature identification in single-cell multi-omics data. Under simulation, OTMODE achieved superior performance (average 90% F1 score; average 92% AUC score) with high efficiency (2.2 s for 5000 cells). In practice, it shows greater sensitivity than other state-of-the-art methods in detecting meaningful processes and can evaluate annotation accuracy by identifying potentially misannotated clusters from auto-annotation tools. Furthermore, OTMODE integrates seamlessly with Scanpy, offering a user-friendly solution for researchers.

OTMODE is freely available at https://github.com/Eggong/OTMODE and also available at https://pypi.org/project/OTMODE/.

## Full-text entities

- **Genes:** HCST (hematopoietic cell signal transducer) [NCBI Gene 10870] {aka DAP10, KAP10, PIK3AP}, UBE2S (ubiquitin conjugating enzyme E2 S) [NCBI Gene 27338] {aka E2-EPF, E2EPF, EPF5}, SNAR-E (small NF90 (ILF3) associated RNA E) [NCBI Gene 100170220], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, RFX1 (regulatory factor X1) [NCBI Gene 5989] {aka EFC, RFX}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}
- **Diseases:** SLE (MESH:D008180), pSS (MESH:D012859)
- **Chemicals:** OTMODE (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC12766913/full.md

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Source: https://tomesphere.com/paper/PMC12766913