# Multi-Beholder: Biomarker Prediction for Low-Grade Glioma with Multiple Instance Learning and One-Class Classification

arXiv: https://arxiv.org/abs/2310.07464 · HTML: https://mlsanity.com/paper/2310.07464/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 14 of its 51 references that are in the map.
- First posted on arXiv 11 Oct 2023.

## Builds on (most cited first, 14 of 14)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [HoVer-Net: Simultaneous Segmentation and Classification of Nuclei in Multi-Tissue Histology Images](https://mlsanity.com/paper/1812.06499/) (2018)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [PanNuke Dataset Extension, Insights and Baselines](https://mlsanity.com/paper/2003.10778/) (2020)
- [Structured State Space Models for Multiple Instance Learning in Digital Pathology](https://mlsanity.com/paper/2306.15789/) (2023)
- [DeepSMILE: Contrastive self-supervised pre-training benefits MSI and HRD classification directly from H&E whole-slide images in colorectal and breast cancer](https://mlsanity.com/paper/2107.09405/) (2021)
- [DOC3-Deep One Class Classification using Contradictions](https://mlsanity.com/paper/2105.07636/) (2021)
- [Creating an Atlas of Normal Tissue for Pruning WSI Patching Through Anomaly Detection](https://mlsanity.com/paper/2310.03106/) (2023)

## Abstract (arXiv)

Biomarker detection is an indispensable part of the diagnosis and treatment of low-grade glioma (LGG). However, current LGG biomarker detection methods rely on expensive and complex molecular genetic testing, for which professionals are required to analyze the results, and intra-rater variability is often reported. To overcome these challenges, we propose an interpretable deep learning pipeline, named Multi-Biomarker Histomorphology Discoverer (Multi-Beholder), to predict the status of five biomarkers in LGG using only hematoxylin and eosin-stained whole slide images. Specifically, Multi-Beholder incorporates one-class classification into the multiple instance learning framework to achieve accurate instance-level pseudo-labeling, thereby complementing slide-level labels and improving prediction performance. Multi-Beholder demonstrates high performance on two LGG cohorts with diverse races and scanning protocols, with area under the receiver operating characteristic curve up to 0.973 on the internal-validated TCGA-LGG dataset and 0.820 on the external-validated Xiangya cohort. Moreover, the interpretability of Multi-Beholder allows for discovering quantitative and qualitative correlations between biomarker status and histomorphology characteristics. Our pipeline not only provides a novel approach for biomarker prediction, enhancing the applicability of molecular treatments for LGG patients but also facilitates the discovery of new mechanisms in molecular functionality and LGG progression. Code can be accessed at https://github.com/Vison307/Multi-Beholder.