# A robust and lightweight deep attention multiple instance learning algorithm for predicting genetic alterations

arXiv: https://arxiv.org/abs/2206.00455 · HTML: https://mlsanity.com/paper/2206.00455/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Builds on 15 of its 57 references that are in the map.
- First posted on arXiv 31 May 2022.

## Builds on (most cited first, 15 of 15)

- [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)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [Xception: Deep Learning with Depthwise Separable Convolutions](https://mlsanity.com/paper/1610.02357/) (2016)
- [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)
- [Not-so-supervised: a survey of semi-supervised, multi-instance, and transfer learning in medical image analysis](https://mlsanity.com/paper/1804.06353/) (2018)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Deep neural network models for computational histopathology: A survey](https://mlsanity.com/paper/1912.12378/) (2019)
- [Multiple Instance Learning: A Survey of Problem Characteristics and Applications](https://mlsanity.com/paper/1612.03365/) (2016)
- [UTNet: A Hybrid Transformer Architecture for Medical Image Segmentation](https://mlsanity.com/paper/2107.00781/) (2021)
- [A Multi-resolution Model for Histopathology Image Classification and Localization with Multiple Instance Learning](https://mlsanity.com/paper/2011.02679/) (2020)
- [Classification and Disease Localization in Histopathology Using Only Global Labels: A Weakly-Supervised Approach](https://mlsanity.com/paper/1802.02212/) (2018)
- [Improving Feature Extraction from Histopathological Images Through A Fine-tuning ImageNet Model](https://mlsanity.com/paper/2201.00636/) (2022)
- [A Retrospective Analysis using Deep-Learning Models for Prediction of Survival Outcome and Benefit of Adjuvant Chemotherapy in Stage II/III Colorectal Cancer](https://mlsanity.com/paper/2111.03532/) (2021)

## Built on by (most cited first, 4 of 4)

- [Predicting microsatellite instability and key biomarkers in colorectal cancer from H&E-stained images: Achieving SOTA predictive performance with fewer data using Swin Transformer](https://mlsanity.com/paper/2208.10495/) (2022)
- [Predicting Genetic Mutation from Whole Slide Images via Biomedical-Linguistic Knowledge Enhanced Multi-label Classification](https://mlsanity.com/paper/2406.02990/) (2024)
- [Finding Regions of Interest in Whole Slide Images Using Multiple Instance Learning](https://mlsanity.com/paper/2404.01446/) (2024)
- [A Systematic Review on the Generative AI Applications in Human Medical Genomics](https://mlsanity.com/paper/2508.20275/) (2025)

## Abstract (arXiv)

Deep-learning models based on whole-slide digital pathology images (WSIs) become increasingly popular for predicting molecular biomarkers. Instance-based models has been the mainstream strategy for predicting genetic alterations using WSIs although bag-based models along with self-attention mechanism-based algorithms have been proposed for other digital pathology applications. In this paper, we proposed a novel Attention-based Multiple Instance Mutation Learning (AMIML) model for predicting gene mutations. AMIML was comprised of successive 1-D convolutional layers, a decoder, and a residual weight connection to facilitate further integration of a lightweight attention mechanism to detect the most predictive image patches. Using data for 24 clinically relevant genes from four cancer cohorts in The Cancer Genome Atlas (TCGA) studies (UCEC, BRCA, GBM and KIRC), we compared AMIML with one popular instance-based model and four recently published bag-based models (e.g., CHOWDER, HE2RNA, etc.). AMIML demonstrated excellent robustness, not only outperforming all the five baseline algorithms in the vast majority of the tested genes (17 out of 24), but also providing near-best-performance for the other seven genes. Conversely, the performance of the baseline published algorithms varied across different cancers/genes. In addition, compared to the published models for genetic alterations, AMIML provided a significant improvement for predicting a wide range of genes (e.g., KMT2C, TP53, and SETD2 for KIRC; ERBB2, BRCA1, and BRCA2 for BRCA; JAK1, POLE, and MTOR for UCEC) as well as produced outstanding predictive models for other clinically relevant gene mutations, which have not been reported in the current literature. Furthermore, with the flexible and interpretable attention-based MIL pooling mechanism, AMIML could further zero-in and detect predictive image patches.