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An integrative deep learning framework for classifying molecular subtypes of breast cancer.

ABSTRACT: Classification of breast cancer subtypes using multi-omics profiles is a difficult problem since the data sets are high-dimensional and highly correlated. Deep neural network (DNN) learning has demonstrated advantages over traditional methods as it does not require any hand-crafted features, but rather automatically extract features from raw data and efficiently analyze high-dimensional and correlated data. We aim to develop an integrative deep learning framework for classifying molecular subtypes of breast cancer. We collect copy number alteration and gene expression data measured on the same breast cancer patients from the Molecular Taxonomy of Breast Cancer International Consortium. We propose a deep learning model to integrate the omics datasets for predicting their molecular subtypes. The performance of our proposed DNN model is compared with some baseline models. Furthermore, we evaluate the misclassification of the subtypes using the learned deep features and explore their usefulness for clustering the breast cancer patients. We demonstrate that our proposed integrative deep learning model is superior to other deep learning and non-deep learning based models. Particularly, we get the best prediction result among the deep learning-based integration models when we integrate the two data sources using the concatenation layer in the models without sharing the weights. Using the learned deep features, we identify 6 breast cancer subgroups and show that Her2-enriched samples can be classified into more than one tumor subtype. Overall, the integrated model show better performance than those trained on individual data sources.

SUBMITTER: Mohaiminul Islam M

PROVIDER: S-EPMC7473884 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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An integrative deep learning framework for classifying molecular subtypes of breast cancer.

Mohaiminul Islam Md M Huang Shujun S Ajwad Rasif R Chi Chen C Wang Yang Y Hu Pingzhao P

Computational and structural biotechnology journal 20200811

Classification of breast cancer subtypes using multi-omics profiles is a difficult problem since the data sets are high-dimensional and highly correlated. Deep neural network (DNN) learning has demonstrated advantages over traditional methods as it does not require any hand-crafted features, but rather automatically extract features from raw data and efficiently analyze high-dimensional and correlated data. We aim to develop an integrative deep learning framework for classifying molecular subtyp ...[more]

PMID: 32952934

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Project description:Background Breast cancer (BC) survival prediction can be a helpful tool for identifying important factors selecting the effective treatment reducing mortality rates. This study aims to predict the time-related survival probability of BC patients in different molecular subtypes over 30 years of follow-up. Materials and methods This study retrospectively analyzed 3580 patients diagnosed with invasive breast cancer (BC) from 1991 to 2021 in the Cancer Research Center of Shahid Beheshti University of Medical Science. The dataset contained 18 predictor variables and two dependent variables, which referred to the survival status of patients and the time patients survived from diagnosis. Feature importance was performed using the random forest algorithm to identify significant prognostic factors. Time-to-event deep-learning-based models, including Nnet-survival, DeepHit, DeepSurve, NMLTR and Cox-time, were developed using a grid search approach with all variables initially and then with only the most important variables selected from feature importance. The performance metrics used to determine the best-performing model were C-index and IBS. Additionally, the dataset was clustered based on molecular receptor status (i.e., luminal A, luminal B, HER2-enriched, and triple-negative), and the best-performing prediction model was used to estimate survival probability for each molecular subtype. Results The random forest method identified tumor state, age at diagnosis, and lymph node status as the best subset of variables for predicting breast cancer (BC) survival probabilities. All models yielded very close performance, with Nnet-survival (C-index=0.77, IBS=0.13) slightly higher using all 18 variables or the three most important variables. The results showed that the Luminal A had the highest predicted BC survival probabilities, while triple-negative and HER2-enriched had the lowest predicted survival probabilities over time. Additionally, the luminal B subtype followed a similar trend as luminal A for the first five years, after which the predicted survival probability decreased steadily in 10- and 15-year intervals. Conclusion This study provides valuable insight into the survival probability of patients based on their molecular receptor status, particularly for HER2-positive patients. This information can be used by healthcare providers to make informed decisions regarding the appropriateness of medical interventions for high-risk patients. Future clinical trials should further explore the response of different molecular subtypes to treatment in order to optimize the efficacy of breast cancer treatments.

Dataset Information

An integrative deep learning framework for classifying molecular subtypes of breast cancer.

Publications

An integrative deep learning framework for classifying molecular subtypes of breast cancer.

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