Dataset Information

Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers.

ABSTRACT:

Introduction

Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance.

Methods

We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predicting individual responses to immunotherapies. ELISE employed iterative univariable logistic regression to select genetic features of patients, using Monte Carlo Tree Search (MCTS) to tune hyperparameters. In each trial, ELISE selected multiple models for integration based on add or concatenate stacking strategies, including deep neural network, automatic feature interaction learning via self-attentive neural networks, deep factorization machine, compressed interaction network, and linear neural network, then adopted the best trial to generate a final approach. SHapley Additive exPlanations (SHAP) algorithm was applied to interpret ELISE, which was then validated in an independent test set.

Result

Regarding prediction of responses to atezolizumab within esophageal adenocarcinoma (EAC) patients, ELISE demonstrated a superior accuracy (Area Under Curve [AUC] = 100.00%). AC005786.3 (Mean [|SHAP value|] = 0.0097) was distinguished as the most valuable contributor to ELISE output, followed by SNORD3D (0.0092), RN7SKP72 (0.0081), EREG (0.0069), IGHV4-80 (0.0063), and MIR4526 (0.0063). Mechanistically, immunoglobulin complex, immunoglobulin production, adaptive immune response, antigen binding and others, were downregulated in ELISE-neg EAC subtypes and resulted in unfavorable responses. More encouragingly, ELISE could be extended to accurately estimate the responsiveness of various immunotherapeutic agents against other cancers, including PD1/PD-L1 suppressor against metastatic urothelial cancer (AUC = 88.86%), and MAGE-A3 immunotherapy against metastatic melanoma (AUC = 100.00%).

Discussion

This study presented deep insights into integrating ensemble deep learning with self-attention as a mechanism for predicting immunotherapy responses to human cancers, highlighting ELISE as a potential tool to generate reliable approaches to individualized treatment.

SUBMITTER: Jin W

PROVIDER: S-EPMC9751999 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers.

Jin Wenyi W Yang Qian Q Chi Hao H Chi Hao H Wei Kongyuan K Zhang Pengpeng P Zhao Guodong G Chen Shi S Xia Zhijia Z Li Xiaosong X

Frontiers in immunology 20221201

<h4>Introduction</h4>Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance.<h4>Methods</h4>We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predictin ...[more]

PMID: 36532083

Similar Datasets

Project description:N6-methyladenosine (m6A) is the most abundant within eukaryotic messenger RNA modification, which plays an essential regulatory role in the control of cellular functions and gene expression. However, it remains an outstanding challenge to detect mRNA m6A transcriptome-wide at base resolution via experimental approaches, which are generally time-consuming and expensive. Developing computational methods is a good strategy for accurate in silico detection of m6A modification sites from the large amount of RNA sequence data. Unfortunately, the existing computational models are usually only for m6A site prediction in a single species, without considering the tissue level of species, while most of them are constructed based on low-confidence level data generated by an m6A antibody immunoprecipitation (IP)-based sequencing method, thereby restricting reliability and generalizability of proposed models. Here, we review recent advances in computational prediction of m6A sites and construct a new computational approach named im6APred using ensemble deep learning to accurately identify m6A sites based on high-confidence level data in multiple tissues of mammals. Our model im6APred builds upon a comprehensive evaluation of multiple classification methods, including four traditional classification algorithms and three deep learning methods and their ensembles. The optimal base-classifier combinations are then chosen by five-fold cross-validation test to achieve an effective stacked model. Our model im6APred can produce the area under the receiver operating characteristic curve (AUROC) in the range of 0.82-0.91 on independent tests, indicating that our model has the ability to learn general methylation rules on RNA bases and generalize to m6A transcriptome-wide identification. Moreover, AUROCs in the range of 0.77-0.96 were achieved using cross-species/tissues validation on the benchmark dataset, demonstrating differences in predictive performance at the tissue level and the need for constructing tissue-specific models for m6A site prediction.

Project description:Classification of different cancer types is an essential step in designing a decision support model for early cancer predictions. Using various machine learning (ML) techniques with ensemble learning is one such method used for classifications. In the present study, various ML algorithms were explored on twenty exome datasets, belonging to 5 cancer types. Initially, a data clean-up was carried out on 4181 variants of cancer with 88 features, and a derivative dataset was obtained using natural language processing and probabilistic distribution. An exploratory dataset analysis using principal component analysis was then performed in 1 and 2D axes to reduce the high-dimensionality of the data. To significantly reduce the imbalance in the derivative dataset, oversampling was carried out using SMOTE. Further, classification algorithms such as K-nearest neighbour and support vector machine were used initially on the oversampled dataset. A 4-layer artificial neural network model with 1D batch normalization was also designed to improve the model accuracy. Ensemble ML techniques such as bagging along with using KNN, SVM and MLPs as base classifiers to improve the weighted average performance metrics of the model. However, due to small sample size, model improvement was challenging. Therefore, a novel method to augment the sample size using generative adversarial network (GAN) and triplet based variational auto encoder (TVAE) was employed that reconstructed the features and labels generating the data. The results showed that from initial scrutiny, KNN showed a weighted average of 0.74 and SVM 0.76. Oversampling ensured that the accuracy of the derivative dataset improved significantly and the ensemble classifier augmented the accuracy to 82.91%, when the data was divided into 70:15:15 ratio (training, test and holdout datasets). The overall evaluation metric value when GAN and TVAE increased the sample size was found to be 0.92 with an overall comparison model of 0.66. Therefore, the present study designed an effective model for classifying cancers which when implemented to real world samples, will play a major role in early cancer diagnosis.

Project description:PurposeFast and accurate outlining of the organs at risk (OARs) and high-risk clinical tumor volume (HRCTV) is especially important in high-dose-rate brachytherapy due to the highly time-intensive online treatment planning process and the high dose gradient around the HRCTV. This study aims to apply a self-configured ensemble method for fast and reproducible auto-segmentation of OARs and HRCTVs in gynecological cancer.Materials and methodsWe applied nnU-Net (no new U-Net), an automatically adapted deep convolutional neural network based on U-Net, to segment the bladder, rectum and HRCTV on CT images in gynecological cancer. In nnU-Net, three architectures, including 2D U-Net, 3D U-Net and 3D-Cascade U-Net, were trained and finally ensembled. 207 cases were randomly chosen for training, and 30 for testing. Quantitative evaluation used well-established image segmentation metrics, including dice similarity coefficient (DSC), 95% Hausdorff distance (HD95%), and average surface distance (ASD). Qualitative analysis of automated segmentation results was performed visually by two radiation oncologists. The dosimetric evaluation was performed by comparing the dose-volume parameters of both predicted segmentation and human contouring.ResultsnnU-Net obtained high qualitative and quantitative segmentation accuracy on the test dataset and performed better than previously reported methods in bladder and rectum segmentation. In quantitative evaluation, 3D-Cascade achieved the best performance in the bladder (DSC: 0.936 ± 0.051, HD95%: 3.503 ± 1.956, ASD: 0.944 ± 0.503), rectum (DSC: 0.831 ± 0.074, HD95%: 7.579 ± 5.857, ASD: 3.6 ± 3.485), and HRCTV (DSC: 0.836 ± 0.07, HD95%: 7.42 ± 5.023, ASD: 2.094 ± 1.311). According to the qualitative evaluation, over 76% of the test data set had no or minor visually detectable errors in segmentation.ConclusionThis work showed nnU-Net's superiority in segmenting OARs and HRCTV in gynecological brachytherapy cases in our center, among which 3D-Cascade shows the highest accuracy in segmentation across different applicators and patient anatomy.

Dataset Information

Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers.

Introduction

Methods

Result

Discussion

Publications

Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets