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Classification with Missing Data - A NIFty Pipeline for Single-Cell Proteomics
Alyssa A Nitz1, Blake McGee1, Benjamin Echarry1
1Department of Biology, Brigham Young University, Provo, Utah, USA.
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
This study introduces NIFty, a novel machine learning method for single-cell proteomics (SCP). NIFty accurately classifies cell types without needing pre-imputed data or batch correction, overcoming common limitations in SCP analysis.
Area of Science:
- Proteomics
- Computational Biology
- Machine Learning
Background:
- Single-cell proteomics (SCP) is crucial for cell-type characterization, trajectory inference, and microenvironment mapping.
- Accurate cell-type annotation in SCP often relies on machine learning, but current methods face challenges with missing data, circular analysis, and batch effects.
- These limitations hinder the reliability and comparability of SCP data analysis.
Purpose of the Study:
- To develop a robust machine learning classification pipeline for single-cell proteomics.
- To address statistical and computational disadvantages of existing SCP annotation methods.
- To improve the accuracy and applicability of cell-type classification in single-cell proteomics experiments.
Main Methods:
- A novel top-scoring pairs based feature selection method, NIFty, was developed.
- NIFty was implemented in a full classification pipeline for single-cell proteomics data.
- The method was evaluated on datasets with missing values, batch effects, and for multiclass classification tasks.
Main Results:
- NIFty successfully classified cell types without requiring pre-imputed data.
- The method demonstrated robustness against significant batch effects without explicit correction.
- NIFty achieved comparable or superior classification accuracy compared to existing methods across varied datasets.
Conclusions:
- NIFty offers a significant advancement in single-cell proteomics data analysis by overcoming key computational and statistical hurdles.
- The method enhances the reliability of cell-type classification, enabling more accurate biological hypothesis evaluation.
- NIFty provides a powerful tool for researchers working with complex single-cell proteomics datasets.

