Published March 7, 2023 | Version v1
Journal article Open

Data augmentation and multimodal learning for predicting drug response in patient-derived xenografts from gene expressions and histology images

  • 1. Argonne National Laboratory
  • 2. University of Chicago
  • 3. Leidos Biomedical Research, Inc.
  • 4. National Cancer Institute

Description

Patient-derived xenografts (PDXs) are an appealing platform for preclinical drug studies. A primary challenge in modeling drug response prediction (DRP) with PDXs and neural networks (NNs) is the limited number of drug response samples. We investigate multimodal neural network (MM-Net) and data augmentation for DRP in PDXs. The MM-Net learns to predict response using drug descriptors, gene expressions (GE), and histology whole-slide images (WSIs). We explore whether combining WSIs with GE improves predictions as compared with models that use GE alone. We propose two data augmentation methods which allow us training multimodal and unimodal NNs without changing architectures with a single larger dataset: 1) combine single-drug and drug-pair treatments by homogenizing drug representations, and 2) augment drug-pairs which doubles the sample size of all drug-pair samples. Unimodal NNs which use GE are compared to assess the contribution of data augmentation. The NN that uses the original and the augmented drug-pair treatments as well as single-drug treatments outperforms NNs that ignore either the augmented drug-pairs or the single-drug treatments. In assessing the multimodal learning based on the MCC metric, MM-Net outperforms all the baselines. Our results show that data augmentation and integration of histology images with GE can improve prediction performance of drug response in PDXs.

Data availability

Publicly available datasets were analyzed in this study. This data can be found at: https://pdmr.cancer.gov/database/default.htm.

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Additional details

Identifiers

DOI
10.3389/fmed.2023.1058919
Other
oai:uchicago.tind.io:5671

Funding

National Cancer Institute-Department of Energy Collaboration
75N91019F00134
Frederick National Laboratory for Cancer Research
75N91019D00024
U.S. Department of Energy
Argonne National Laboratory
U.S. Department of Energy
Lawrence Livermore National Laboratory
U.S. Department of Energy
Los Alamos National Laboratory
U.S. Department of Energy
Oak Ridge National Laboratory

UChicago Information

Division(s)
Biological Sciences Division, Physical Sciences Division
Department(s)
Computer Science, Medicine