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M4: Multi-proxy multi-gate mixture of experts network for multiple instance learning in histopathology image

Junyu Li1, Ye Zhang2, Wen Shu3

  • 1Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.

Medical Image Analysis
|April 8, 2025
PubMed
Summary

This study introduces M4, a novel multiple instance learning framework for analyzing whole slide images (WSIs). M4 enables simultaneous prediction of multiple genetic mutations from WSIs, improving efficiency and capturing inter-task relationships.

Keywords:
Genetic mutationMulti-task learningMultiple instance learningWhole slide image

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Area of Science:

  • Computational pathology
  • Artificial intelligence in medicine
  • Digital pathology

Background:

  • Multiple instance learning (MIL) is crucial for whole slide images (WSIs) analysis in computational pathology.
  • Current MIL methods often focus on single tasks, limiting efficiency and overlooking task interdependencies.

Purpose of the Study:

  • To develop an efficient MIL framework for simultaneous prediction of multiple genetic mutations from WSIs.
  • To address the limitations of single-task learning in computational pathology.

Main Methods:

  • Proposed an adapted architecture: Multi-gate Mixture-of-experts with Multi-proxy for Multiple instance learning (M4).
  • Implemented a multi-gate mixture-of-experts strategy for simultaneous prediction of multiple genetic mutations.
  • Introduced a multi-proxy CNN for expert and gate networks to capture patch-patch interactions within WSIs.

Main Results:

  • M4 demonstrated significant improvements across five TCGA datasets.
  • Achieved superior performance compared to state-of-the-art single-task MIL methods.
  • Successfully enabled simultaneous prediction of multiple genetic mutations from WSIs.

Conclusions:

  • The M4 framework offers an efficient and effective approach for multi-task learning in WSI analysis.
  • M4 captures inter-task relatedness, outperforming single-task methods.
  • This work advances computational pathology by enabling simultaneous prediction of multiple biomarkers from WSIs.