Deep learning (DL) is one of the best approaches to predict nonlinear behaviors from high dimensional data. Nevertheless predicting the outcome of patients affected by cancers from transcriptomic data has shown limited performance, even with DL (C-index usually <0.65). Transfer learning is a DL two-step method where a model is pre-trained for a basic task on large amount of data, and then fine-tuned on the aimed task. We hypothesized that using TL with RNAseq may improve the performances of cancer patients’ outcome estimation.
The model was a Multi-Mayer Perceptron (MLP) with 22913 inputs corresponding to genes bulk tumor whole genome RNAseq expression analysis. An important restriction was applied to the number of units at second layer (N = 100), with further linear decrease across subsequent layers. Architecture of the model (number of layers, skip connections), L1 normalization value and learning rate were optimized by grid search on 30 parallel models. Training was performed using Keras package in R. Data were split into 70% training, 15% cross validation, 15% validation for each step, without contamination between the 2 transfer learning steps. The pre-training step consisted in predicting the organs of sample origin using 17.487 public RNAseq data of normal & cancer tissues (GTEX from gtexportal.org & TCGA from cBioportal.org). Fine-tuning on patients survival used 6401 training tumors. The model’s performance on survival prediction was evaluated by C-index and the area under the survival receiver-operating characteristic curve (AUROC).
The pre-training using GTEx and TCGA reached very high performance with validation accuracy of 0.96 to predict organ of origins for the best model (all models had validation accuracy > 0.9). Fine-tuning on survival, the prognostic performance of the best model on the validation cohort was C-index=0.74 and AUROC= 0.81 (80% of models had a C-index > 0.6). The best model had 8 hidden layers and a small penalization value.
Thanks to this original transfer learning method, we achieved a high performance to estimate cancer patients’ prognostic from whole genome expression, a classically challenging task. Learning on public databases is a valuable method of DL for personalized cancer care.
The authors.
Has not received any funding.
E. Angevin: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: DebioPharma; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Lilly; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Orion. A. Hollebecque: Advisory / Consultancy: Amgen; Advisory / Consultancy: Spectrum Pharmaceuticals; Advisory / Consultancy: Lilly; Advisory / Consultancy: Debiopharm; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Incyte; Travel / Accommodation / Expenses: Debiopharm. E. Deutsch: Advisory / Consultancy: Boehringer; Advisory / Consultancy: Medimune; Advisory / Consultancy: Amgen; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): biotrachea; Research grant / Funding (institution): BristolMyersSquidd; Research grant / Funding (self): Clevelex; Research grant / Funding (self): EDF; Research grant / Funding (self): Lilly; Research grant / Funding (self): GlaxoSmisthKline; Research grant / Funding (self): Merk; Research grant / Funding (self): Nanobiotix; Research grant / Funding (self): Oseo; Research grant / Funding (self): Ray Search Laboratory; Research grant / Funding (self): Roche; Research grant / Funding (self): Ipsen; Research grant / Funding (self): Servier; Research grant / Funding (self): Takeda. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: DebioPharma; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Lilly; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Orion. L. Verlingue: Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Adaptherapy. All other authors have declared no conflicts of interest.