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Trajectory-informed gene feature selection in single-cell analysis with SEEK-VFI
Rebecca Danning1, Zheng Tracy Ke2, Xihong Lin3
1Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Reports Methods
|July 27, 2026
Summary
SEEK-VFI is a new machine learning method that identifies important genes for understanding cell development. It improves trajectory inference and analysis by prioritizing relevant genes over uninformative ones.
Area of Science:
- Computational Biology
- Machine Learning
- Genomics
Background:
- Identifying highly variable genes is crucial for single-cell trajectory inference.
- Standard methods struggle to distinguish trajectory-relevant genes from noise in continuous cell development.
- This limitation impacts the accuracy of inferring cellular progression.
Purpose of the Study:
- To develop an improved method for prioritizing trajectory-relevant genes in single-cell data.
- To address the limitations of existing methods in continuous developmental trajectories.
- To enhance the preprocessing step for trajectory inference algorithms.
Main Methods:
- Introduced SEEK-VFI (Spectral Ensembling of topic models with Eigenscore for K-agnostic Variable Feature Identification).
- Utilized an ensemble topic modeling approach with eigenscore for gene prioritization.
- Applied machine learning for trajectory inference preprocessing.
Main Results:
- SEEK-VFI outperforms existing methods in identifying trajectory-relevant genes.
- The method successfully differentiates informative genes from uninformative ones.
- Identified key genes that significantly improve trajectory topology reconstruction and visualization.
Conclusions:
- SEEK-VFI provides a robust solution for gene prioritization in single-cell trajectory inference.
- The identified genes enhance downstream trajectory analyses and biological interpretation.
- This approach advances the field of computational biology and single-cell data analysis.
Keywords:
CP: computational biologyensemble learningfeature selectionsingle-cell analysistopic modelingtrajectory inference
